Journal articles on the topic 'Ischemia, paired pulse facilitation, hippocampus'
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Tanaka, E., S. Yasumoto, G. Hattori, S. Niiyama, S. Matsuyama, and H. Higashi. "Mechanisms Underlying the Depression of Evoked Fast EPSCs Following In Vitro Ischemia in Rat Hippocampal CA1 Neurons." Journal of Neurophysiology 86, no. 3 (September 1, 2001): 1095–103. http://dx.doi.org/10.1152/jn.2001.86.3.1095.
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The mechanisms underlying the depression of evoked fast excitatory postsynaptic currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in vitro ischemia) for a 4-min period in hippocampal CA1 neurons were investigated in rat brain slices. The amplitude of evoked fast EPSCs decreased by 85 ± 7% of the control 4 min after the onset of in vitro ischemia. In contrast, the exogenous glutamate-induced inward currents were augmented, while the spontaneous miniature EPSCs obtained in the presence of tetrodotoxin (TTX, 1 μM) did not change in amplitude during in vitro ischemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pulse stimulation (40-ms interval), and the amplitude of the second fast EPSC increased to 156 ± 24% of the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio) increased during in vitro ischemia. Pretreatment of the slices with adenosine 1 (A1) receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the depression of the fast EPSCs, in a concentration-dependent manner: in the presence of 8-CPT (1–10 μM), the amplitude of the fast EPSCs decreased by only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic volleys and excitatory postsynaptic field potentials (fEPSPs) were extracellularly recorded in a proximal part of the stratum radiatum in the CA1 region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On the other hand, the amplitudes of the first and second presynaptic volley, which were abolished by TTX (0.5 μM), did not change during in vitro ischemia. The maximal slope of the Ca2+-dependent action potential of the CA3 neurons, which were evoked in the presence of 8-CPT (1 μM), nifedipine (20 μM), TTX (0.5 μM), and tetraethyl ammonium chloride (20 mM), decreased by 12 ± 6% of the control 4 min after the onset of in vitro ischemia. These results suggest that in vitro ischemia depresses the evoked fast EPSCs mainly via the presynaptic A1 receptors, and the remaining 8-CPT–resistant depression of the fast EPSCs is probably due to a direct inhibition of the Ca2+ influx to the axon terminals.
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Nathan, T., and J. D. Lambert. "Depression of the fast IPSP underlies paired-pulse facilitation in area CA1 of the rat hippocampus." Journal of Neurophysiology 66, no. 5 (November 1, 1991): 1704–15. http://dx.doi.org/10.1152/jn.1991.66.5.1704.
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1. Intracellular recordings from CA1 pyramidal neurons in the rat hippocampal slice have been used to study synaptic transmission after maximal orthodromic stimulation of the Schaffer collateral-commissural fibers. Paired-pulse stimulation was used to investigate how the first (conditioning) stimulation influenced the response to the second (test) stimulation. 2. When the test stimulation was delivered up to approximately 4 s after the conditioning stimulation, the late phase of the excitatory postsynaptic synaptic potential (EPSP) was increased (“late-phase facilitation”) whereas the fast (f-) and the slow (s-) inhibitory postsynaptic potentials (IPSPs) were depressed. 3. In terms of appearance and time course, facilitation of the intracellularly recorded EPSP was similar to that of the extracellularly recorded field EPSP in stratum radiatum. 4. The s-IPSP is not involved in facilitation of the EPSP. To show this, we counteracted the s-IPSP either by repolarizing the membrane potential to the resting level or by intracellularly injecting the quaternary lignocaine derivative QX 314. Facilitation of the late phase of the EPSP was unaffected by either procedure. 5. The conditioned response was modified in two ways when the stimulation was delivered at the equilibrium potential for the f-IPSP (Ef-IPSP) and the s-IPSP had been blocked by intracellular injection of QX 314. The amplitude of the EPSP was increased, and the repolarizing phase was delayed with an apparent depolarizing shift of Ef-IPSP. This effect was present at pulse intervals greater than 20 ms and was maximal after 150 ms. Facilitation could be detected at interpulse intervals of up to 4 s. 6. The gamma-aminobutyric acid-B (GABAB) agonist baclofen (1 microM) reduced late-phase facilitation by preferentially increasing the unconditioned response, such that this came to resemble a conditioned response in control medium. 7. The f-IPSP was isolated pharmacologically to investigate its role in the facilitation of the EPSP. This was done by blocking the s-IPSP with QX314 and the EPSP with a mixture of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovaleric acid (APV, 50 microM), and the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). An f-IPSP was then evoked by stimulating the interneurons directly. This potential could be blocked by the GABAA receptor antagonist bicuculline (20 microM), thereby confirming the successful isolation of GABAAergic transmission. 8. With paired-pulse stimulation, the amplitude of the conditioned f-IPSP was depressed.(ABSTRACT TRUNCATED AT 400 WORDS)
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Buonomano, Dean V., and Michael M. Merzenich. "Net Interaction Between Different Forms of Short-Term Synaptic Plasticity and Slow-IPSPs in the Hippocampus and Auditory Cortex." Journal of Neurophysiology 80, no. 4 (October 1, 1998): 1765–74. http://dx.doi.org/10.1152/jn.1998.80.4.1765.
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Buonomano, Dean V. and Michael M. Merzenich. Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex. J. Neurophysiol. 80: 1765–1774, 1998. Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of γ-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally “erased” short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.
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Saviane, Chiara, Leonid P. Savtchenko, Giacomo Raffaelli, Leon L. Voronin, and Enrico Cherubini. "Frequency‐dependent shift from paired‐pulse facilitation to paired‐pulse depression at unitary CA3‐CA3 synapses in the rat hippocampus." Journal of Physiology 544, no. 2 (October 2002): 469–76. http://dx.doi.org/10.1113/jphysiol.2002.026609.
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Sui, Li, and M. E. Gilbert. "Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus." Endocrinology 144, no. 9 (September 1, 2003): 4195–203. http://dx.doi.org/10.1210/en.2003-0395.
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Abstract Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.
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Tanner, Kylie M., Chinyere Obasi, Ian A. Herrick, and L. Stan Leung. "Effects of Propofol on Hippocampal Synaptic Transmission in Behaving Rats." Anesthesiology 93, no. 2 (August 1, 2000): 463–72. http://dx.doi.org/10.1097/00000542-200008000-00026.
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Background The action of propofol has been studied in vitro and in vivo, but the effects of intravenously administered propofol on synaptic transmission in freely behaving rats have not been studied before. Methods Rats were implanted with recording electrodes in the dentate gyrus and with stimulation electrodes in the medial perforant path (MPP). Paired pulses at different interpulse intervals (IPIs) were delivered to the MPP, and average evoked potentials were recorded in the dentate gyrus before and after a bolus of propofol (10 or 20 mg/kg administered intravenously) or control vehicle was injected via femoral vein cannula. Because of the layered structure of the hippocampus, population excitatory postsynaptic potentials and population spikes could be distinguished and analyzed. Results Propofol has no significant effect on the population excitatory postsynaptic potentials or population spike evoked by a single MPP stimulus pulse. However, paired-pulse inhibition of the dentate population spikes was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the population spike was most prominent when tail pinch response was lost (deep and moderate anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired-pulse facilitation of population spikes was observed during moderate anesthesia in most rats. Conclusions In freely behaving rats, intravenous propofol enhanced paired-pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric acid A receptor-mediated inhibition. Propofol also increased paired-pulse facilitation at 200 ms IPI through an unknown mechanism, which may contribute to the neuroexcitatory effect of propofol.
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Ferchmin, P. A., P. G. DiScenna, E. M. Rivera, V. A. Eterović, and T. J. Teyler. "26. Spermine increases paired-pulse facilitation in area CA1 of hippocampus: Effect of calcium." Journal of Neuroscience Methods 52, no. 1 (April 1994): A12. http://dx.doi.org/10.1016/0165-0270(94)90086-8.
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Andreasen, M., and J. J. Hablitz. "Paired-pulse facilitation in the dentate gyrus: a patch-clamp study in rat hippocampus in vitro." Journal of Neurophysiology 72, no. 1 (July 1, 1994): 326–36. http://dx.doi.org/10.1152/jn.1994.72.1.326.
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1. Whole-cell patch-clamp recordings were used to study paired-pulse facilitation (PPF) of the lateral perforant path input to the dentate gyrus in thin hippocampal slices. 2. Orthodromic stimulation of the lateral perforant pathway evoked a excitatory postsynaptic current (EPSC) with a latency of 3.3 +/- 0.1 ms (mean +/- SE) that fluctuated in amplitude. The EPSC had a rise time (10-90%) of 2.79 +/- 0.06 ms (n = 35) and decayed with a single exponential time course with a time-constant of 9.14 +/- 0.24 ms (n = 35). No correlation was found between the amplitude of the EPSC and the rise time or decay time-constant. The non-N-methyl-D-aspartate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione completely blocked the EPSC whereas the NMDA antagonist D-aminophosphonovaleric acid (APV) had modest effects. 3. When a test (T-)EPSC was preceded at an interval of 100 ms by a conditioning (C-)EPSC, a significant increase in the amplitude of the T-EPSC was seen in 38 out of 44 trials analyzed from a total of 27 granule cells. The average amount of PPF was 35.7 +/- 2.1%. There was no apparent correlation between the amount of PPF and the stimulation intensity or mean amplitude of the C-EPSC. The time course of the facilitated T-EPSC was not significantly different from that of the C-EPSC. 4. No correlation was found between the amplitude of the C-EPSC and that of the T-EPSC. Estimates of quantal content (mcv) were determined by calculating the ratio of the squared averaged EPSC amplitude (from 48 responses) to the variance of these responses (M2/sigma 2) whereas quantal amplitudes (qcv) were estimated by calculating the ratio of the response variance to average EPSC amplitude (sigma 2/M). PPF was found to be associated with an average increase in mcv of 64.8 +/- 7.2% (n = 38) whereas qcv was decreased by 12.1 +/- 3.8%. 5. The time course of PPF was studied by varying the interval between the C- and T-pulse from 10 to 400 ms while keeping the stimulation intensity constant. Maximal facilitation of the T-EPSC was obtained with interpulse intervals < or = 25 ms where the average facilitation amounted to approximately 70% (n = 6). The decline of facilitation was nearly exponential and was no longer evident with intervals > 350 ms.(ABSTRACT TRUNCATED AT 400 WORDS
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Takamatsu, Isao, Ayano Iwase, Makoto Ozaki, Tomiei Kazama, Keiji Wada, and Masayuki Sekiguchi. "Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus." Anesthesiology 108, no. 1 (January 1, 2008): 94–102. http://dx.doi.org/10.1097/01.anes.0000296076.04510.e1.
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Background Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective alpha2-adrenergic agonist that also has affinity for imidazoline receptors. In clinical studies, dexmedetomidine has sedative effects and impairs memory, but the action of dexmedetomidine on synaptic plasticity in the brain has yet to be established. In the present study, the authors investigated the effects of dexmedetomidine on two forms of synaptic plasticity-long-term potentiation (LTP) and paired-pulse facilitation-in the CA1 region of mouse hippocampal slices. Methods The authors recorded Schaffer collateral-evoked field excitatory postsynaptic potentials from mouse hippocampal slices in CA1 stratum radiatum. The slope of the rising phase of the field excitatory postsynaptic potential was used to estimate the strength of synaptic transmission. Results Application of dexmedetomidine for 20 min before "theta burst" stimulation dose-dependently attenuated LTP, and half-inhibitory concentration of dexmedetomidine was 28.6 +/- 5.7 nm. The inhibitory effect of dexmedetomidine on LTP was not abolished by an alpha2-adrenoceptor antagonist (yohimbine), an imidazoline type 1 receptor and alpha2-adrenoceptor antagonist (efaroxan), an alpha1-adrenoceptor antagonist (prazosin), or a gamma-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and alpha2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetomidine-induced attenuation. Furthermore, 2-benzofuranyl-2-imidaloline, a selective imidazoline type 2 receptor ligand, reduced LTP. 2-(4,5-dihydroimidaz-2-yl)-quinoline, another imidazoline type 2 receptor ligand, abolished the 2-benzofuranyl-2-imidaloline-induced attenuation, but the inhibitory effect of dexmedetomidine on LTP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation. Conclusion Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha2-adrenoceptors.
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Ferchmin, P. A., Vesna A. Eterović, Edna M. Rivera, and Timothy J. Teyler. "Spermine increases paired-pulse facilitation in area CA1 of hippocampus in a calcium-dependent manner." Brain Research 689, no. 2 (August 1995): 189–96. http://dx.doi.org/10.1016/0006-8993(95)00568-b.
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Debanne, D., N. C. Guérineau, B. H. Gähwiler, and S. M. Thompson. "Paired pulse facilitation and depression at unitary excitatory synapses in the rat hippocampus in vitro." Journal of Physiology-Paris 88, no. 6 (January 1994): 378. http://dx.doi.org/10.1016/0928-4257(94)90044-2.
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Cho, In Ha, Lauren C. Panzera, Morven Chin, Scott A. Alpizar, Genaro E. Olveda, Robert A. Hill, and Michael B. Hoppa. "The potassium channel subunit Kvβ1 serves as a major control point for synaptic facilitation." Proceedings of the National Academy of Sciences 117, no. 47 (November 9, 2020): 29937–47. http://dx.doi.org/10.1073/pnas.2000790117.
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Analysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca2+in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 blocked all broadening of the APsynduring high-frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus, using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic Kvchannels in synaptic facilitation at presynaptic terminals of the hippocampus upstream of the exocytic machinery.
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Pairojana, Tanita, Sarayut Phasuk, Pavithra Suresh, and Ingrid Y. Liu. "Behavioral and Synaptic Phenotypes of Female Prdx6−/− Mice." Antioxidants 11, no. 6 (June 19, 2022): 1201. http://dx.doi.org/10.3390/antiox11061201.
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Peroxiredoxin 6 (PRDX6) is expressed throughout the brain, including the hippocampus, where it plays a potential role in synaptic regulation and forming emotional and spatial memories. PRDX6 is predominantly detected in the female mouse’s hippocampus; thus, we investigate the effect of the Prdx6 gene on behavioral phenotypes and synaptic functions using female Prdx6 knockout (Prdx6−/−) mice. Our results demonstrate that female Prdx6−/− mice exhibited anxiety-like behavior, enhanced contextual fear memory, and impaired spatial memory. We also found increased, paired–pulse facilitation ratios, and decreased long-term potentiation (LTP) in the hippocampal region of these female Prdx6−/− mice. The present study helps to understand better the PRDX6’s role in emotional response and spatial memory formation in female mice.
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Debanne, D., N. C. Guérineau, B. H. Gähwiler, and S. M. Thompson. "Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release." Journal of Physiology 491, no. 1 (February 15, 1996): 163–76. http://dx.doi.org/10.1113/jphysiol.1996.sp021204.
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Vreugdenhil, Martin, John G. R. Jefferys, Marco R. Celio, and Beat Schwaller. "Parvalbumin-Deficiency Facilitates Repetitive IPSCs and Gamma Oscillations in the Hippocampus." Journal of Neurophysiology 89, no. 3 (March 1, 2003): 1414–22. http://dx.doi.org/10.1152/jn.00576.2002.
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In the hippocampus, the calcium-binding protein parvalbumin (PV) is expressed in interneurons that innervate perisomatic regions. PV in GABAergic synaptic terminals was proposed to limit repetitive GABA release by buffering of “residual calcium.” We assessed the role of presynaptic PV in Ca2+-dependent GABA release in the hippocampus of PV-deficient (PV−/−) mice and wild-type (PV+/+) littermates. Pharmacologically isolated inhibitory postsynaptic currents (IPSCs) were evoked by low-intensity stimulation of the stratum pyramidale and recorded from voltage-clamped CA1 pyramidal neurons. The amplitude and decay time constant of single IPSCs were similar for both genotypes. Under our experimental conditions of reduced release probability and minimal presynaptic suppression, paired-pulse facilitation of IPSCs occurred at intervals from 2 to 50 ms, irrespective of the presence of PV. The facilitation of IPSCs induced by trains of 10 stimuli at frequencies >20 Hz was enhanced in cells from PV−/− mice, the largest difference between PV−/− and PV+/+ animals (220%) being observed at 33 Hz. The effect of IPSC facilitation at sustained gamma frequencies was assessed on kainate-induced rhythmic IPSC-paced neuronal oscillations at gamma frequencies, recorded with dual field potential recordings in area CA3. The maximum power of the oscillation was 138 μV2 at 36 Hz in slices from PV+/+ mice and was trebled in slices from PV−/− mice. PV deficiency caused a similar increase in gamma power under conditions used to study IPSC facilitation and can be explained by an increased facilitation of GABA release at sustained high frequencies. The dominant frequency and coherence were not affected by PV deficiency. These observations suggest that PV deficiency, due to an increased short-term facilitation of GABA release, enhances inhibition by high-frequency burst-firing PV-expressing interneurons and may affect the higher cognitive functions associated with gamma oscillations.
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Goodell, Dayton J., Tim A. Benke, and K. Ulrich Bayer. "Developmental restoration of LTP deficits in heterozygous CaMKIIα KO mice." Journal of Neurophysiology 116, no. 5 (November 1, 2016): 2140–51. http://dx.doi.org/10.1152/jn.00518.2016.
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The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory and cognition. The heterozygous CaMKIIα isoform KO (CaMKIIα+/−) mice have a schizophrenia-related phenotype, including impaired working memory. Here, we examined synaptic strength and plasticity in two brain areas implicated in working memory, hippocampus CA1 and medial prefrontal cortex (mPFC). Young CaMKIIα+/− mice (postnatal days 12–16; corresponding to a developmental stage well before schizophrenia manifestation in humans) showed impaired hippocampal CA1 LTP. However, this LTP impairment normalized over development and was no longer detected in older CaMKIIα+/− mice (postnatal weeks 9–11; corresponding to young adults). By contrast, the CaMKIIα+/− mice failed to show the developmental increase of basal synaptic transmission in the CA1 seen in wild-type (WT) mice, resulting in impaired basal synaptic transmission in the older CaMKIIα+/− mice. Other electrophysiological parameters were normal, including mPFC basal transmission, LTP, and paired-pulse facilitation, as well as CA1 LTD, depotentiation, and paired-pulse facilitation at either age tested. Hippocampal CaMKIIα levels were ∼60% of WT in both the older CaMKIIα+/− mice and in the younger WT mice, resulting in ∼30% of adult WT expression in the younger CaMKIIα+/− mice; levels in frontal cortex were the same as in hippocampus. Thus, in young mice, ∼30% of adult CaMKIIα expression is sufficient for normal LTD and depotentiation, while normal LTP requires higher levels, with ∼60% of CaMKIIα expression sufficient for normal LTP in adult mice.
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Capogna, M., B. H. Gahwiler, and S. M. Thompson. "Calcium-independent actions of alpha-latrotoxin on spontaneous and evoked synaptic transmission in the hippocampus." Journal of Neurophysiology 76, no. 5 (November 1, 1996): 3149–58. http://dx.doi.org/10.1152/jn.1996.76.5.3149.
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1. The black widow spider venom component, alpha-latrotoxin (alpha-LTx) (< 0.5 nM), increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in hippocampal CA3 pyramidal cells 14-fold, without changing their amplitude. 2. This action of alpha-LTx was not affected by application of Ca(2+)-free/ethylene glycol-bis(b-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing saline, 100 microM Cd2+, or 50 microM Gd3+. The increase in mEPSC frequency was thus not due to an influx of Ca2+ into the axon terminal via voltage-dependent Ca2+ channels or alpha-LTx-induced pores. 3. alpha-LTx did not increase spontaneous release when synaptic transmission had been impaired by botulinum toxin/F. 4. alpha-LTx reduced the amplitude of EPSCs, elicited with stimulation of mossy fibers, without affecting paired-pulse facilitation. 5. The Ca2+ ionophore ionomycin (2–2.5 microM) also enhanced the frequency of mEPSCs, but unlike alpha-LTx, potentiated evoked EPSCs and reduced paired-pulse facilitation. Application of N-methyl-D-aspartate elicited a high frequency of Ca(2+)-dependent, tetrodotoxin-sensitive spontaneous EPSCs, but did not affect evoked EPSC amplitude. Agents that stimulate vesicular release by increasing presynaptic Ca2+ influx thus do not mimic the alpha-LTx-induced depression of evoked EPSCs. 6. We conclude that entry of Ca2+ into presynaptic axon terminals is not responsible for the effects of low concentrations of alpha-LTx on either spontaneous or evoked transmitter release in the hippocampus. 7. Potential presynaptic mechanisms that could mediate the opposing actions of alpha-LTx on spontaneous and evoked transmitter release in the hippocampus (i.e., alpha-LTx-induced ionic pores, depletion of synaptic vesicles, actions on exocytotic proteins) are discussed.
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Nathan, T., M. S. Jensen, and J. D. C. Lambert. "GABAB receptors play a major role in paired-pulse facilitation in area CA1 of the rat hippocampus." Brain Research 531, no. 1-2 (October 1990): 55–65. http://dx.doi.org/10.1016/0006-8993(90)90757-3.
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A. Samara, Maria, George D. Oikonomou, George Trompoukis, Georgia Madarou, Maria Adamopoulou, and Costas Papatheodoropoulos. "Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABAB receptors in the rat hippocampus." Brain and Neuroscience Advances 6 (January 2022): 239821282211063. http://dx.doi.org/10.1177/23982128221106315.
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Short-term synaptic plasticity represents a fundamental mechanism in neural information processing and is regulated by neuromodulators. Here, using field recordings from the CA1 region of adult rat hippocampal slices, we show that excitatory synaptic transmission is suppressed by strong but not moderate activation of adenosine A1 receptors by 2-Chloro-N6-cyclopentyladenosine (CCPA) more in the dorsal than the ventral hippocampus; in contrast, both mild and strong activation of GABAB receptors by baclofen (1 μM, 10 μM) suppress synaptic transmission more in the ventral than the dorsal hippocampus. Using a 10-pulse stimulation train of variable frequency, we found that CCPA modulates short-term synaptic plasticity independently of the suppression of synaptic transmission in both segments of the hippocampus and at stimulation frequencies greater than 10 Hz. However, specifically regarding the paired-pulse ratio (PPR) and frequency facilitation/depression (FF/D) we found significant drug action before but not after adjusting conditioning responses to control levels. Activation of GABABRs by baclofen suppressed synaptic transmission more in the ventral than the dorsal hippocampus. Furthermore, relatively high (10 μM) but not low (1 μM) baclofen concentration enhanced both PPR and FF in both hippocampal segments at stimulation frequencies greater than 1 Hz, independently of the suppression of synaptic transmission by baclofen. These results show that A1Rs and GABABRs control synaptic transmission more effectively in the dorsal and the ventral hippocampus, respectively, and suggest that these receptors modulate PPR and FF/D at different frequency bands of afferent input, in both segments of the hippocampus.
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Colgin, Laura Lee, Enikö A. Kramár, Christine M. Gall, and Gary Lynch. "Septal Modulation of Excitatory Transmission in Hippocampus." Journal of Neurophysiology 90, no. 4 (October 2003): 2358–66. http://dx.doi.org/10.1152/jn.00262.2003.
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Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.
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Wasling, P., E. Hanse, and B. Gustafsson. "Developmental Changes in Release Properties of the CA3-CA1 Glutamate Synapse in Rat Hippocampus." Journal of Neurophysiology 92, no. 5 (November 2004): 2714–24. http://dx.doi.org/10.1152/jn.00464.2004.
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Developmental changes in release probability ( Pr) and paired–pulse plasticity at CA3-CA1 glutamate synapses in hippocampal slices of neonatal rats were examined using field excitatory postsynaptic potential (EPSP) recordings. Paired-pulse facilitation (PPF) at these synapses was, on average, absent in the first postnatal week but emerged and became successively larger during the second postnatal week. This developmental increase in PPF was associated with a reduction in Pr, as indicated by the slower progressive block of the N-methyl-d-aspartate (NMDA) EPSP by the noncompetitive NMDA receptor antagonist MK-801. This developmental reduction in Pr was not homogenous among the synapses. As shown by the MK-801 analysis, the Pr heterogeneity observed among adult CA3-CA1 synapses is present already during the first postnatal week, and the developmental Pr reduction was found to be largely selective for synapses with higher Pr values, leaving Pr of the vast majority of the synapses essentially unaffected. A reduction in Pves, the release probability of the individual vesicle, possibly caused by reduction in Ca2+ influx, seems to explain the reduction in Pr. In vivo injection of tetanus toxin at the end of the first postnatal week did not prevent the increase in PPF, indicating that this developmental change in release is not critically dependent on normal neural activity during the second postnatal week.
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Clark, K. A., A. D. Randall, and G. L. Collingridge. "A comparison of paired-pulse facilitation of AMPA and NMDA receptor-mediated excitatory postsynaptic currents in the hippocampus." Experimental Brain Research 101, no. 2 (September 1994): 272–78. http://dx.doi.org/10.1007/bf00228747.
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Stubblefield, Elizabeth A., and Tim A. Benke. "Distinct AMPA-Type Glutamatergic Synapses in Developing Rat CA1 Hippocampus." Journal of Neurophysiology 104, no. 4 (October 2010): 1899–912. http://dx.doi.org/10.1152/jn.00099.2010.
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We assessed synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) properties during synaptogenesis to describe the development of individual glutamatergic synapses on rat hippocampal CA1 principal neurons. Pharmacologically isolated AMPAR-mediated glutamatergic synaptic currents [evoked by stimulation of the Schaffer Collateral pathway, excitatory postsynaptic currents (EPSCs)], had significantly greater inward-rectification at ages P5–7 compared with P8–18. These inward rectifying EPSCs demonstrated paired-pulse dependent unblocking at positive holding potentials, consistent with voltage-dependent internal polyamine block. Measurements of paired-pulse facilitation did not support altered presynaptic properties associated with inward rectification. Using asynchronous EPSCs (aEPSCs) to analyze populations of individual synapses, we found that quantal amplitudes ( Q) increased across early postnatal development (P5-P18) and were directly modulated by increases in the number of activated receptors. Quantal AMPAR decay kinetics (aEPSC τdecays) exhibited the highest coefficient of variation (CV) from P5 to 7 and became markedly less variable at P8–18. At P5–7, faster quantal kinetics coexisted with much slower kinetics; only slower quantal kinetics were found at P8–18. This supports diverse quantal synaptic properties limited to P5–7. Multivariate cluster analysis of Q, CVτdecay, and median τdecay supported a segregation of neurons into two distinct age groups of P5–7 and P8–18, similar to the age-related segregation suggested by inward rectification. Taken together, these findings support synaptic, calcium permeable AMPARs at a subset of synapses onto CA1 pyramidal neurons exclusively at P5–7. These distinct synapses coexist with those sharing the properties of more mature synapses. These synapses disappear after P7 as activated receptor numbers increase with age.
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Cazakoff, Brittany N., and John G. Howland. "Acute stress disrupts paired pulse facilitation and long-term potentiation in rat dorsal hippocampus through activation of glucocorticoid receptors." Hippocampus 20, no. 12 (November 24, 2010): 1327–31. http://dx.doi.org/10.1002/hipo.20738.
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Kudryashova, I. V., I. E. Kudryashov, and N. V. Gulyaeva. "Long-term potentiation in the hippocampus in conditions of inhibition of caspase-3: Analysis of facilitation in paired-pulse stimulation." Neuroscience and Behavioral Physiology 36, no. 8 (October 2006): 817–24. http://dx.doi.org/10.1007/s11055-006-0092-y.
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Pofantis, Hermes, Panagiotis Georgopoulos, Theodoros Petrides, and Costas Papatheodoropoulos. "Differences in paired-pulse inhibition and facilitation in the dentate gyrus and CA3 field between dorsal and ventral rat hippocampus." Brain Research 1608 (May 2015): 21–30. http://dx.doi.org/10.1016/j.brainres.2015.03.003.
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Voronin, L. L., A. V. Rossokhin, and M. V. Sokolov. "Intracellular studies of the interaction between paired-pulse facilitation and the delayed phase of long-term potentiation in the hippocampus." Neuroscience and Behavioral Physiology 29, no. 3 (May 1999): 347–54. http://dx.doi.org/10.1007/bf02465348.
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Zhang, Yuchun, Ping Deng, Yan Li, and Zao C. Xu. "Enhancement of Excitatory Synaptic Transmission in Spiny Neurons After Transient Forebrain Ischemia." Journal of Neurophysiology 95, no. 3 (March 2006): 1537–44. http://dx.doi.org/10.1152/jn.01166.2005.
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Spiny neurons in the neostriatum are highly vulnerable to ischemia. Enhancement of excitatory synaptic transmissions has been implicated in ischemia-induced excitotoxic neuronal death. Here we report that evoked excitatory postsynaptic currents in spiny neurons were potentiated after transient forebrain ischemia. The ischemia-induced potentiation in synaptic efficacy was associated with an enhancement of presynaptic release as demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and a decrease in the paired-pulse ratio. The amplitude of inward currents evoked by exogenous application of glutamate did not show significant changes after ischemia, suggesting that postsynaptic mechanism is not involved. The ischemia-induced increase in mEPSCs frequency was not affected by blockade of voltage-gated calcium channels, but it was eliminated in the absence of extracellular calcium. Bath application of ATP P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) significantly reduced mEPSC frequency in ischemic neurons but had no effects on the control ones. Furthermore, the inhibitory effect of PPADS on ischemic neurons was abolished in Ca2+-free external solution. These results indicate that excitatory synaptic transmissions in spiny neurons are potentiated after ischemia via presynaptic mechanisms. Activation of P2X receptors and the consequent Ca2+ influx might contribute to the ischemia-induced facilitation of glutamate release.
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Sun, H. Y., A. F. Bartley, and L. E. Dobrunz. "Calcium-Permeable Presynaptic Kainate Receptors Involved in Excitatory Short-Term Facilitation Onto Somatostatin Interneurons During Natural Stimulus Patterns." Journal of Neurophysiology 101, no. 2 (February 2009): 1043–55. http://dx.doi.org/10.1152/jn.90286.2008.
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Schaffer collateral synapses in hippocampus show target-cell specific short-term plasticity. Using GFP-expressing Inhibitory Neuron (GIN) transgenic mice that express enhanced green fluorescent protein (EGFP) in a subset of somatostatin-containing interneurons (SOM interneurons), we previously showed that Schaffer collateral synapses onto SOM interneurons in stratum (S.) radiatum have unusually large (up to 6-fold) paired-pulse facilitation. This results from a low initial release probability and the enhancement of facilitation by synaptic activation of presynaptic kainate receptors. Here we further investigate the properties of these kainate receptors and examine their effects on short-term facilitation during physiologically derived stimulation patterns, using excitatory postsynaptic currents recorded in S. radiatum interneurons during Schaffer collateral stimulation in acute slices from juvenile GIN mice. We find that GluR5 and GluR6 antagonists decrease short-term facilitation at Schaffer collateral synapses onto SOM interneurons with no additive effects, suggesting that the presynaptic kainate receptors are heteromers containing both GluR5 and GluR6 subunits. The calcium-permeable receptor antagonist 1-napthyl acetyl spermine (NASPM) both mimics and occludes the effect of the kainate receptor antagonists, indicating that the presynaptic kainate receptors are calcium permeable. Furthermore, Schaffer collateral synapses onto SOM interneurons show up to 11-fold short-term facilitation during physiologically derived stimulus patterns, in contrast to other interneurons that have less than 1.5-fold facilitation. Blocking the kainate receptors reduces facilitation in SOM interneurons by ∼50% during the physiologically derived patterns and reduces the dynamic range. Activation of calcium-permeable kainate receptors containing GluR5/GluR6 causes a dramatic increase in short-term facilitation during physiologically derived stimulus patterns, a mechanism likely to be important in regulating the strength of Schaffer collateral synapses onto SOM interneurons in vivo.
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Son, Hyeon, and David O. Carpenter. "Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus." Synapse 23, no. 4 (August 1996): 302–11. http://dx.doi.org/10.1002/(sici)1098-2396(199608)23:4<302::aid-syn8>3.0.co;2-b.
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Fischer, Marc, Julia Reuter, Florian J. Gerich, Belinda Hildebrandt, Sonja Hägele, Dörthe Katschinski, and Michael Müller. "Enhanced Hypoxia Susceptibility in Hippocampal Slices From a Mouse Model of Rett Syndrome." Journal of Neurophysiology 101, no. 2 (February 2009): 1016–32. http://dx.doi.org/10.1152/jn.91124.2008.
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Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-chromosomal MECP2 gene encoding for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). Rett patients suffer from episodic respiratory irregularities and reduced arterial oxygen levels. To elucidate whether such intermittent hypoxic episodes induce adaptation/preconditioning of the hypoxia-vulnerable hippocampal network, we analyzed its responses to severe hypoxia in adult Rett mice. The occurrence of hypoxia-induced spreading depression (HSD)—an experimental model for ischemic stroke—was hastened in Mecp2− /y males. The extracellular K+ rise during HSD was attenuated in Mecp2− /y males and the input resistance of CA1 pyramidal neurons decreased less before HSD onset. CA1 pyramidal neurons were smaller and more densely packed, but the cell swelling during HSD was unaffected. The intrinsic optical signal and the propagation of HSD were similar among the different genotypes. Basal synaptic function was intact, but Mecp2− /y males showed reduced paired-pulse facilitation and higher field potential/fiber volley ratios, but no increased seizure susceptibility. Synaptic failure during hypoxia was complete in all genotypes and the final degree of posthypoxic synaptic recovery indistinguishable. Cellular ATP content was normal in Mecp2− /y males, but their hematocrit was increased as was HIF-1α expression throughout the brain. This is the first study showing that in Rett syndrome, the susceptibility of telencephalic neuronal networks to hypoxia is increased; the underlying molecular mechanisms apparently involve disturbed K+ channel function. Such an increase in hypoxia susceptibility may potentially contribute to the vulnerability of male Rett patients who are either not viable or severely disabled.
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González-H, Guillermo, Itzel Jatziri Contreras-García, Karla Sánchez-Huerta, Claudio M. T. Queiroz, Luis Ricardo Gallardo Gudiño, Julieta G. Mendoza-Torreblanca, and Sergio R. Zamudio. "Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy." Brain Sciences 10, no. 9 (September 11, 2020): 634. http://dx.doi.org/10.3390/brainsci10090634.
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Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.
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Faivre, Emilie, Victor A. Gault, Bernard Thorens, and Christian Hölscher. "Glucose-dependent insulinotropic polypeptide receptor knockout mice are impaired in learning, synaptic plasticity, and neurogenesis." Journal of Neurophysiology 105, no. 4 (April 2011): 1574–80. http://dx.doi.org/10.1152/jn.00866.2010.
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Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone, released from intestine after a meal, producing a glucose-dependent insulin secretion. The GIP receptor (GIPR) is expressed on pyramidal neurons in the cortex and hippocampus, and GIP is synthesized in a subset of neurons in the brain. However, the role of the GIPR in neuronal signaling is not clear. In this study, we used a mouse strain with GIPR gene deletion (GIPR KO) to elucidate the role of the GIPR in neuronal communication and brain function. Compared with C57BL/6 control mice, GIPR KO mice displayed higher locomotor activity in an open-field task. Impairment of recognition and spatial learning and memory of GIPR KO mice were found in the object recognition task and a spatial water maze task, respectively. In an object location task, no impairment was found. GIPR KO mice also showed impaired synaptic plasticity in paired-pulse facilitation and a block of long-term potentiation in area CA1 of the hippocampus. Moreover, a large decrease in the number of neuronal progenitor cells was found in the dentate gyrus of transgenic mice, although the numbers of young neurons was not changed. Together the results suggest that GIP receptors play an important role in cognition, neurotransmission, and cell proliferation.
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Tidball, Patrick, Hannah V. Burn, Kai Lun Teh, Arturas Volianskis, Graham L. Collingridge, and Stephen M. Fitzjohn. "Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor–dependent synaptic and intrinsic plasticity." Brain and Neuroscience Advances 1 (January 1, 2017): 239821281668979. http://dx.doi.org/10.1177/2398212816689792.
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Background: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role. Methods: In this study, we have used extracellular field potential recordings to compare basal input/output function and group I metabotropic glutamate receptor-dependent forms of synaptic and intrinsic plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the adult rat hippocampus. Results: Using two extracellular electrodes to simultaneously record field EPSPs and population spikes, we show that dorsal and ventral hippocampal slices differ in their basal levels of excitatory synaptic transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore, we show that slices taken from the ventral hippocampus have a greater ability than their dorsal counterparts to exhibit long-term depression of synaptic transmission and EPSP-to-Spike potentiation induced by transient application of the group I mGluR agonist ( RS)-3,5-dihydroxyphenylglycine. Conclusions: Together, our results provide further evidence that the information processing properties of local hippocampal circuits differ in the dorsal and ventral hippocampal sectors, and that these differences may in turn contribute to the functional differentiation that exists along the hippocampal longitudinal axis.
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Nishikawa, Koh-ichi, and M. Bruce MacIver. "Excitatory Synaptic Transmission Mediated by NMDA Receptors Is More Sensitive to Isoflurane than Are Non-NMDA Receptor-mediated Responses." Anesthesiology 92, no. 1 (January 1, 2000): 228. http://dx.doi.org/10.1097/00000542-200001000-00035.
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Background Effects of volatile anesthetic agents on N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic transmission have not been well characterized. The authors compared effects produced by halothane and isoflurane on electrophysiologic properties of NMDA and non-NMDA receptor-mediated synaptic responses in slices from the rat hippocampus. Methods Field excitatory postsynaptic potentials (fEPSPs) in the CA1 area were recorded with extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. NMDA or non-NMDA receptor-mediated fEPSPs were pharmacologically isolated using selective antagonists. Clinically relevant concentrations of halothane or isoflurane were applied to slices in an artificial cerebrospinal fluid perfusate. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic agents. Results Clinically relevant concentrations of halothane (1.2 vol% approximately 0.35 mM) depressed fEPSP amplitudes mediated by NMDA receptors and non-NMDA receptors to a similar degree (mean +/- SD: 63.3 +/- 14.0% of control, n = 5; 60.2 +/- 7.3% of control, n = 7, respectively). In contrast, isoflurane (1.4 vol% approximately 0.50 mM) preferentially depressed fEPSP amplitudes mediated by NMDA receptors (44.0 +/- 7.4% of control, n = 6, P < 0.001) compared with those for non-NMDA receptors (68.7 +/- 5.4% of control n = 6), indicating a selective, additional postsynaptic effect. Paired pulse facilitation of fEPSPs was increased significantly by both anesthetic agents from 1.37 +/- 0.13 to 1.91 +/- 0.25 (n = 5, P < 0.05 for halothane) and from 1.44 +/- 0.04 to 1.64 +/- 0.08 (n = 5, P < 0.01 for isoflurane), suggesting that presynaptic mechanisms are also involved in fEPSP depression produced by the anesthetic agents. Neither rise times nor decay times of fEPSPs were changed in the presence of the anesthetic agents. Conclusions These results indicate that fEPSPs mediated by postsynaptic NMDA receptors are more sensitive to clinically relevant concentrations of isoflurane than are non-NMDA receptor-mediated responses, but this selective effect was not observed for halothane. Both agents also appeared to depress release of glutamate from nerve terminals via presynaptic actions.
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Manabe, T., D. J. Wyllie, D. J. Perkel, and R. A. Nicoll. "Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus." Journal of Neurophysiology 70, no. 4 (October 1, 1993): 1451–59. http://dx.doi.org/10.1152/jn.1993.70.4.1451.
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1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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Wu, LG, and P. Saggau. "Presynaptic calcium is increased during normal synaptic transmission and paired-pulse facilitation, but not in long-term potentiation in area CA1 of hippocampus." Journal of Neuroscience 14, no. 2 (February 1, 1994): 645–54. http://dx.doi.org/10.1523/jneurosci.14-02-00645.1994.
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Fernández-Fernández, Diego, Holger Rosenbrock, and Katja S. Kroker. "Inhibition of PDE2A, but not PDE9A, modulates presynaptic short-term plasticity measured by paired-pulse facilitation in the CA1 region of the hippocampus." Synapse 69, no. 10 (July 29, 2015): 484–96. http://dx.doi.org/10.1002/syn.21840.
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Sullivan, Jane M. "Mechanisms of Cannabinoid-Receptor–Mediated Inhibition of Synaptic Transmission in Cultured Hippocampal Pyramidal Neurons." Journal of Neurophysiology 82, no. 3 (September 1, 1999): 1286–94. http://dx.doi.org/10.1152/jn.1999.82.3.1286.
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Cannabinoids, such as marijuana, are known to impair learning and memory perhaps through their actions in the hippocampus where cannabinoid receptors are expressed at high density. Although cannabinoid receptor activation decreases glutamatergic synaptic transmission in cultured hippocampal neurons, the mechanisms of this action are not known. Cannabinoid receptor activation also inhibits calcium channels that support neurotransmitter release in these cells, making modulation of these channels a candidate for cannabinoid-receptor–mediated effects on synaptic transmission. Whole cell patch-clamp recordings of glutamatergic neurons cultured from the CA1 and CA3 regions of the hippocampus were used to identify the mechanisms of the effects of cannabinoids on synaptic transmission. Cannabinoid receptor activation reduced excitatory postsynaptic current (EPSC) size by ∼50% but had no effect on the amplitude of spontaneous miniature EPSCs (mEPSCs). This reduction in EPSC size was accompanied by an increase in paired-pulse facilitation measured in low (1 mM) extracellular calcium and by a decrease in paired-pulse depression measured in normal (2.5 mM) extracellular calcium. Together, these results strongly support the hypothesis that cannabinoid receptor activation decreases EPSC size by reducing release of neurotransmitter presynaptically while having no effect on postsynaptic sensitivity to glutamate. Further experiments were done to identify the molecular mechanisms underlying this cannabinoid-receptor–mediated decrease in neurotransmitter release. Cannabinoid receptor activation had no effect on the size of the presynaptic pool of readily releasable neurotransmitter-filled vesicles, eliminating reduction in pool size as a mechanism for cannabinoid-receptor–mediated effects. After blockade of Q- and N-type calcium channels with ω-agatoxin TK and ω-conotoxin GVIA; however, activation of cannabinoid receptors reduced EPSC size by only 14%. These results indicate that cannabinoid receptor activation reduces the probability that neurotransmitter will be released in response to an action potential via an inhibition of presynaptic Q- and N-type calcium channels. This molecular mechanism most likely contributes to the impairment of learning and memory produced by cannabinoids and may participate in the analgesic, antiemetic, and anticonvulsive effects of these drugs as well.
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Albiñana, Elisa, Javier Gutierrez-Luengo, Natalia Hernández-Juarez, Andrés M. Baraibar, Eulalia Montell, Josep Vergés, Antonio G. García, and Jesus M. Hernández-Guijo. "Chondroitin Sulfate Induces Depression of Synaptic Transmission and Modulation of Neuronal Plasticity in Rat Hippocampal Slices." Neural Plasticity 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/463854.
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It is currently known that in CNS the extracellular matrix is involved in synaptic stabilization and limitation of synaptic plasticity. However, it has been reported that the treatment with chondroitinase following injury allows the formation of new synapses and increased plasticity and functional recovery. So, we hypothesize that some components of extracellular matrix may modulate synaptic transmission. To test this hypothesis we evaluated the effects of chondroitin sulphate (CS) on excitatory synaptic transmission, cellular excitability, and neuronal plasticity using extracellular recordings in the CA1 area of rat hippocampal slices. CS caused a reversible depression of evoked field excitatory postsynaptic potentials in a concentration-dependent manner. CS also reduced the population spike amplitude evoked after orthodromic stimulation but not when the population spikes were antidromically evoked; in this last case a potentiation was observed. CS also enhanced paired-pulse facilitation and long-term potentiation. Our study provides evidence that CS, a major component of the brain perineuronal net and extracellular matrix, has a function beyond the structural one, namely, the modulation of synaptic transmission and neuronal plasticity in the hippocampus.
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Kusakari, Shinya, Fumihito Saitow, Yukio Ago, Koji Shibasaki, Miho Sato-Hashimoto, Yasunori Matsuzaki, Takenori Kotani, et al. "Shp2 in Forebrain Neurons Regulates Synaptic Plasticity, Locomotion, and Memory Formation in Mice." Molecular and Cellular Biology 35, no. 9 (February 23, 2015): 1557–72. http://dx.doi.org/10.1128/mcb.01339-14.
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Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K+-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.
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Shang, Yingchun, Xin Wang, Fangjuan Li, Tao Yin, Jianhai Zhang, and Tao Zhang. "rTMS Ameliorates Prenatal Stress–Induced Cognitive Deficits in Male-Offspring Rats Associated With BDNF/TrkB Signaling Pathway." Neurorehabilitation and Neural Repair 33, no. 4 (April 2019): 271–83. http://dx.doi.org/10.1177/1545968319834898.
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Background. Growing evidences suggest that brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) plays a key role in the regulation of hippocampal synaptic plasticity in a prenatal stress (PNS) rat model. Repetitive transcranial magnetic stimulation (rTMS) is currently being acknowledged to affect attention and memory in both preclinical and clinical studies, although the mechanism is still unclear. Objective. The current study aimed to explore whether a whole brain rTMS (5 Hz, 14 days) could ameliorate cognitive dysfunction–induced PNS in male offspring, and examine if the positive effect of rTMS was associated with the BDNF/TrkB signaling in the hippocampus. Methods. The rats were randomly divided into 5 groups: CON, PNS, PNS + rTMS, PNS + rTMS + DMSO (dimethyl sulfoxide), and PNS + rTMS + K252a. Spatial cognition was evaluated by using Morris water maze test. Following behavioral assessment, both paired-pulse facilitation and long-term potentiation were recorded from Schaffer collaterals to CA1 region in the hippocampus. Synaptic, apoptotic, and BDNF/TrkB signaling proteins were measured by Western blot. Results. PNS-exposed offspring exhibited cognitive deficits, long-term potentiation inhibition in the hippocampus, the decrease of synaptic and BDNF/TrkB signaling proteins expression, apoptosis, and reduced number of cells in the CA1 region. Five-hertz rTMS significantly alleviated the PNS-induced abnormalities. However, the effect of rTMS was antagonized by intracerebroventricular infusion of K252a (a TrkB inhibitor). Conclusions. The findings suggest that 5-Hz rTMS significantly improves the impairment of spatial cognition and hippocampal synaptic plasticity, which is possibly associated with the activation of BDNF/TrkB signaling.
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Shors, Tracey J., and Richard F. Thompson. "Acute stress impairs (or induces) synaptic long-term potentiation (LTP) but does not affect paired-pulse facilitation in the stratum radiatum of rat hippocampus." Synapse 11, no. 3 (July 1992): 262–65. http://dx.doi.org/10.1002/syn.890110311.
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Mahmoud, Ghada S., and Lawrence M. Grover. "Growth Hormone Enhances Excitatory Synaptic Transmission in Area CA1 of Rat Hippocampus." Journal of Neurophysiology 95, no. 5 (May 2006): 2962–74. http://dx.doi.org/10.1152/jn.00947.2005.
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The hippocampus produces growth hormone (GH) and contains GH receptors, suggesting a potential role for GH signaling in the regulation of hippocampal function. In agreement with this possibility, previous investigations have found altered hippocampal function and hippocampal-dependent learning and memory after chronic GH administration or deficiency. In this study we applied GH to in vitro rat hippocampal brain slices, to determine whether GH has short-term effects on hippocampal function in addition to previously documented chronic effects. We found that GH enhanced both AMPA- and NMDA-receptor–mediated excitatory postsynaptic potentials (EPSPs) in hippocampal area CA1, but did not alter GABAA-receptor–mediated inhibitory synaptic transmission. GH enhancement of excitatory synaptic transmission was gradual, requiring 60–70 min to reach maximum, and occurred without any change in paired-pulse facilitation, suggesting a possible postsynaptic site of action. In CA1 pyramidal neurons, GH enhancement of EPSPs was correlated with significant hyperpolarization and decreased input resistance. GH enhancement of EPSPs required Janus kinase 2 (JAK2), phosphatidylinositol-3 (PI3) kinase, mitogen-activated protein (MAP) kinase kinase (MEK), and synthesis of new proteins. Although PI3 kinase and MEK were required for initiation of GH effects on excitatory synaptic transmission, they were not required for maintained enhancement of EPSPs. GH treatment and tetanus-induced long-term potentiation were mutually occluding, suggesting a common mechanism or mechanisms in both forms of synaptic enhancement. Our results demonstrate that GH has powerful short-term effects on hippocampal function, and extend the timescale for potential roles of GH in regulating hippocampal function and hippocampal-dependent behaviors.
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Roberto, M., T. E. Nelson, C. L. Ur, and D. L. Gruol. "Long-Term Potentiation in the Rat Hippocampus Is Reversibly Depressed by Chronic Intermittent Ethanol Exposure." Journal of Neurophysiology 87, no. 5 (May 1, 2002): 2385–97. http://dx.doi.org/10.1152/jn.2002.87.5.2385.
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Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have serious long-term consequences on CNS function including cognitive effects and attenuation of learning and memory. The cellular mechanisms underlying the CNS effects of alcohol have yet to be fully elucidated and are likely to depend on the pattern and dose of alcohol exposure. Using electrophysiological recordings from hippocampal slices obtained from control and chronic alcohol-treated rats, we have investigated the effects of a binge pattern of alcohol abuse on synaptic plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor for 12–14 days using an intermittent exposure paradigm (14 h ethanol exposure/10 h ethanol withdrawal daily; blood alcohol levels ∼180 mg/dl), a paradigm that models human binge alcohol use. Induction of long-term potentiation (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer collaterals was completely blocked in slices from the chronic alcohol-treated animals. LTP remained blocked 1 day after withdrawal of animals from alcohol, indicating that the neuroadaptive changes produced by alcohol were not readily reversible. Partial recovery was observed after withdrawal from alcohol for 5 days. Other measures of synaptic plasticity including posttetanic potentiation and paired-pulse facilitation were also altered by the intermittent alcohol treatment paradigm. The results suggest that alterations in synaptic plasticity induced by chronic intermittent ethanol consumption play an important role in the effects of binge alcohol use on learning and memory function.
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Maltsev, Alexander V., Natalia V. Bal, and Pavel M. Balaban. "Serine/Threonine Phosphatases in LTP: Two B or Not to Be the Protein Synthesis Blocker-Induced Impairment of Early Phase." International Journal of Molecular Sciences 22, no. 9 (May 4, 2021): 4857. http://dx.doi.org/10.3390/ijms22094857.
Full textAbstract:
Dephosphorylation of target proteins at serine/threonine residues is one of the most crucial mechanisms regulating their activity and, consequently, the cellular functions. The role of phosphatases in synaptic plasticity, especially in long-term depression or depotentiation, has been reported. We studied serine/threonine phosphatase activity during the protein synthesis blocker (PSB)-induced impairment of long-term potentiation (LTP). Established protein phosphatase 2B (PP2B, calcineurin) inhibitor cyclosporin A prevented the LTP early phase (E-LTP) decline produced by pretreatment of hippocampal slices with cycloheximide or anisomycin. For the first time, we directly measured serine/threonine phosphatase activity during E-LTP, and its significant increase in PSB-treated slices was demonstrated. Nitric oxide (NO) donor SNAP also heightened phosphatase activity in the same manner as PSB, and simultaneous application of anisomycin + SNAP had no synergistic effect. Direct measurement of the NO production in hippocampal slices by the NO-specific fluorescent probe DAF-FM revealed that PSBs strongly stimulate the NO concentration in all studied brain areas: CA1, CA3, and dentate gyrus (DG). Cyclosporin A fully abolished the PSB-induced NO production in the hippocampus, suggesting a close relationship between nNOS and PP2B activity. Surprisingly, cyclosporin A alone impaired short-term plasticity in CA1 by decreasing paired-pulse facilitation, which suggests bi-directionality of the influences of PP2B in the hippocampus. In conclusion, we proposed a minimal model of signaling events that occur during LTP induction in normal conditions and the PSB-treated slices.
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Ma, Long, Gerald Reis, Luis F. Parada, and Erin M. Schuman. "Neuronal NT-3 Is not Required For Synaptic Transmission or Long-Term Potentiation in Area CA1 of the Adult Rat Hippocampus." Learning & Memory 6, no. 3 (May 1, 1999): 267–75. http://dx.doi.org/10.1101/lm.6.3.267.
Full textAbstract:
Neurotrophic factors, including BDNF and NT-3, have been implicated in the regulation of synaptic transmission and plasticity. Previous attempts to analyze synaptic transmission and plasticity in mice lacking the NT-3 gene have been hampered by the early death of the NT-3 homozygous knockout animals. We have bypassed this problem by examining synaptic transmission in mice in which the NT-3 gene is deleted in neurons later in development, by crossing animals expressing the CRE recombinase driven by the synapsin I promoter to animals in which the NT-3 gene is floxed. We conducted blind field potential recordings at the Schaffer collateral–CA1 synapse in hippocampal slices from homozygous knockout and wild-type mice. We examined the following indices of synaptic transmission: (1) input-output relationship; (2) paired-pulse facilitation; (3) post-tetanic potentiation; and (4) long-term potentiation: induced by two different protocols: (a) two trains of 100-Hz stimulation and (b) theta burst stimulation. We found no difference between the knockout and wild-type mice in any of the above measurements. These results suggest that neuronal NT-3 does not play an essential role in normal synaptic transmission and some forms of plasticity in the mouse hippocampus.
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Kawai, Kensuke, LaRoy P. Penix, Nobutaka Kawahara, Christl A. Ruetzler, and Igor Klatzo. "Development of Susceptibility to Audiogenic Seizures following Cardiac Arrest Cerebral Ischemia in Rats." Journal of Cerebral Blood Flow & Metabolism 15, no. 2 (March 1995): 248–58. http://dx.doi.org/10.1038/jcbfm.1995.31.
Full textAbstract:
Susceptibility to audiogenic seizures (AGS) was investigated in Sprague–Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of >5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed ∼50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of γ-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked ∼1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.
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Kessey, Kofi, and David J. Mogul. "NMDA-Independent LTP by Adenosine A2 Receptor-Mediated Postsynaptic AMPA Potentiation in Hippocampus." Journal of Neurophysiology 78, no. 4 (October 1, 1997): 1965–72. http://dx.doi.org/10.1152/jn.1997.78.4.1965.
Full textAbstract:
Kessey, Kofi and David J. Mogul. NMDA-independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus. J. Neurophysiol. 78: 1965–1972, 1997. The role of adenosine A2 receptors in normal synaptic transmission and tetanus-induced long-term potentiation (LTP) was tested by stimulation of the Schaffer collateral pathway and recording of the field excitatory postsynaptic potential (EPSP) in the CA1 region of rat transverse hippocampal slices. Activation of adenosine A2 receptors with the A2 agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic transmission during low-frequency test pulses (0.033 Hz). Paired stimulation before and during DPMA exposure indicated no paired-pulse facilitation as a result of A2 activation, suggesting that enhancement was not a result of presynaptic modulation. DPMA enhanced the early phase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the EPSP. In contrast, DPMA had no effect on the N-methyl-d-aspartate (NMDA) component isolated using low extracellular Mg2+ and the AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM), indicating that the effects of A2 activation on synaptic transmission were mediated by a postsynaptic enhancement of the AMPA response. Activation of adenosine A2 receptors during a brief tetanus (100 Hz, 1 s) increased the level of LTP by 36% over that seen in response to a tetanus under control conditions. DPMA exposure after prior induction of LTP showed no additional potentiation, indicating that the mechanisms that contribute to both types of increases in synaptic transmission share a common mechanism. A slow onset NMDA-independent LTP could be induced by application of a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 μM). Blockade of L-type Ca channels with nifedipine (10 μM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP could be induced after prior saturation of NMDA-dependent LTP via multiple tetani spaced 10 min apart, indicating that both forms of LTP are eventually convergent on a common mechanism, presumably the postsynaptic AMPA receptor response. Because extracellular adenosine levels are modulated by cellular activity throughout the brain and because adenosine receptor activation can markedly alter levels of synaptic transmission independent of NMDA receptors, adenosine may play an important and complex role as a modulator of synaptic transmission in the brain.
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Terada, Sumio, Tetsuhiro Tsujimoto, Yosuke Takei, Tomoyuki Takahashi, and Nobutaka Hirokawa. "Impairment of Inhibitory Synaptic Transmission in Mice Lacking Synapsin I." Journal of Cell Biology 145, no. 5 (May 31, 1999): 1039–48. http://dx.doi.org/10.1083/jcb.145.5.1039.
Full textAbstract:
Deletion of the synapsin I genes, encoding one of the major groups of proteins on synaptic vesicles, in mice causes late onset epileptic seizures and enhanced experimental temporal lobe epilepsy. However, mice lacking synapsin I maintain normal excitatory synaptic transmission and modulation but for an enhancement of paired-pulse facilitation. To elucidate the cellular basis for epilepsy in mutants, we examined whether the inhibitory synapses in the hippocampus from mutant mice are intact by electrophysiological and morphological means. In the cultured hippocampal synapses from mutant mice, repeated application of a hypertonic solution significantly suppressed the subsequent transmitter release, associated with an accelerated vesicle replenishing time at the inhibitory synapses, compared with the excitatory synapses. In the mutants, morphologically identifiable synaptic vesicles failed to accumulate after application of a hypertonic solution at the inhibitory preterminals but not at the excitatory preterminals. In the CA3 pyramidal cells in hippocampal slices from mutant mice, inhibitory postsynaptic currents evoked by direct electrical stimulation of the interneuron in the striatum oriens were characterized by reduced quantal content compared with those in wild type. We conclude that synapsin I contributes to the anchoring of synaptic vesicles, thereby minimizing transmitter depletion at the inhibitory synapses. This may explain, at least in part, the epileptic seizures occurring in the synapsin I mutant mice.