Inhibitory Nature of Tiagabine-Augmented GABAAReceptor–Mediated Depolarizing Responses in Hippocampal Pyramidal Cells

1999 ◽  
Vol 81 (3) ◽  
pp. 1192-1198 ◽  
Author(s):  
Michael F. Jackson ◽  
Barbara Esplin ◽  
Radan C̆apek
Keyword(s):  
High Frequency ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Gaba Uptake ◽  
Conditioning Stimulation ◽  
Whole Cell ◽  
Inhibitory Pathways ◽  
Bath Application ◽  
Whole Cell Recordings ◽  
Stimulation Of

Inhibitory nature of tiagabine-augmented GABAA receptor–mediated depolarizing responses in hippocampal pyramidal cells. Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant activity. GABA uptake inhibitors are believed to produce their anticonvulsant effects by prolonging the postsynaptic actions of GABA, released during episodes of neuronal hyperexcitability. However, tiagabine has recently been reported to facilitate the depolarizing actions of GABA in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity. In the present study, we performed extracellular and whole cell recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the functional consequences of tiagabine-augmented GABA-mediated depolarizing responses. Orthodromic population spikes (PSs), elicited from the stratum radiatum, were inhibited following the activation of recurrent inhibitory pathways by antidromic conditioning stimulation of the alveus, which consisted of either a single stimulus or a train of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which was always of much greater strength and duration than that produced by a single conditioning stimulus, was greatly enhanced following the bath application of tiagabine (2–100 μM). Thus, in the presence of tiagabine (20 μM), orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 ± 2.6% (mean ± SE) and 34.4 ± 18.5% of their unconditioned amplitudes compared with only 35.4 ± 12.7% and 98.8 ± 12.4% in control. Whole cell recordings revealed that the bath application of tiagabine (20 μM) either caused the appearance or greatly enhanced the amplitude of GABA-mediated depolarizing responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum radiatum at time points that coincided with the DR were inhibited to below the threshold for action-potential firing. Independently of the stimulus intensity with which they were evoked, the charge transferred to the soma by excitatory postsynaptic currents (EPSCs), elicited in the presence of tiagabine (20 μM) during the large (1,428 ± 331 pA) inward currents that underlie the DRs, was decreased on the average by 90.8 ± 1.7%. Such inhibition occurred despite the presence of the GABAB receptor antagonist, CGP 52 432 (10 μM), indicating that GABAB heteroreceptors, located on glutamatergic terminals, do not mediate the observed reduction in the amplitude of excitatory postsynaptic responses. The present results suggest that despite facilitating the induction of GABA-mediated depolarizations, tiagabine application may nevertheless increase the effectiveness of synaptic inhibition during the synchronous high-frequency activation of inhibitory interneurons by enhanced shunting.

scholarly journals Activity-dependent differences in function between proximal and distal Schaffer collaterals

2015 ◽  
Vol 113 (10) ◽  
pp. 3646-3662 ◽  
Author(s):  
Benjamin Owen ◽  
Lawrence M. Grover
Keyword(s):  
High Frequency ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Burst Stimulation ◽  
Schaffer Collateral ◽  
Whole Cell ◽  
Schaffer Collaterals

Axon conduction fidelity is important for signal transmission and has been studied in various axons, including the Schaffer collateral axons of the hippocampus. Previously, we reported that high-frequency stimulation (HFS) depresses Schaffer collateral excitability when assessed by whole-cell recordings from CA3 pyramidal cells but induces biphasic excitability changes (increase followed by decrease) in extracellular recordings of CA1 fiber volleys. Here, we examined responses from proximal (whole-cell or field-potential recordings from CA3 pyramidal cell somata) and distal (field-potential recordings from CA1 stratum radiatum) portions of the Schaffer collaterals during HFS and burst stimulation in hippocampal slices. Whole-cell and dual-field-potential recordings using 10–100-Hz HFS revealed frequency-dependent changes like those previously described, with higher frequencies producing more drastic changes. Dual-field-potential recordings revealed substantial differences in the response to HFS between proximal and distal regions of the Schaffer collaterals, with proximal axons depressing more strongly and only distal axons showing an initial excitability increase. Because CA3 pyramidal neurons normally fire in short bursts rather than long high-frequency trains, we repeated the dual recordings using 100–1,000-ms interval burst stimulation. Burst stimulation produced changes similar to those during HFS, with shorter intervals causing more drastic changes and substantial differences observed between proximal and distal axons. We suggest that functional differences between proximal and distal Schaffer collaterals may allow selective filtering of nonphysiological activity while maximizing successful conduction of physiological activity throughout an extensive axonal arbor.

Membrane Potential of CA3 Hippocampal Pyramidal Cells During Postnatal Development

2003 ◽  
Vol 90 (5) ◽  
pp. 2964-2972 ◽  
Author(s):  
Roman Tyzio ◽  
Anton Ivanov ◽  
Cristophe Bernard ◽  
Gregory L. Holmes ◽  
Yehezkiel Ben-Ari ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Postnatal Development ◽  
Developmental Change ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Whole Cell ◽  
Perforated Patch ◽  
Ca3 Pyramidal Cells ◽  
Whole Cell Recordings

A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was –44 ± 4 (SE) mV at postnatal days P0–P2, and it progressively shifted to –67 ± 2 mV at P13–15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was –77 ± 2 mV at P2 and –77 ± 2 mV at P13–14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.

Spontaneous GABAA receptor-mediated inhibitory currents in adult rat somatosensory cortex

1996 ◽  
Vol 75 (4) ◽  
pp. 1573-1588 ◽  
Author(s):  
P. A. Salin ◽  
D. A. Prince
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Decay Time ◽  
High Frequency ◽  
Pyramidal Cells ◽  
Receptor Activation ◽  
Inhibitory Interneurons ◽  
Adult Rat ◽  
Bath Application

1. Spontaneous inhibitory synaptic currents (sIPSCs) were studied with whole cell voltage-clamp recordings from 131 pyramidal cells in adult rat somatosensory cortical slices. Neurons were intracellulary labeled with biocytin and classified as supragranular (SG, layers 2-3), layer IV (IV), or infragranular (IG, layer V) on the basis of the laminar localization of their somata. Somatic areas were similar for SG, IV, and IG neurons. All identified pyramidal cells generated high-frequency gamma-aminobutyric acid (GABAA) receptor-mediated synaptic events. 2. Bath application of bicuculline blocked the sIPSCs and resulted in a decrease of approximately 0.5 nS in resting conductance and an inward shift in baseline current. 3. sIPSC frequency was significantly lower in SG versus IG or IV neurons, and this difference was accounted for by the occurrence of a higher percentage of bursts of sIPSCs in the IG and IV neurons. 4. Bath application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased the frequency of sIPSCs by 13-21%. By contrast, application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) generally had no effect on spontaneous IPSC frequency, suggesting that AMPA rather than NMDA receptor activation contributed to resting discharge of inhibitory interneurons. 5. Addition of tetrodotoxin (TTX) to the perfusion medium reduced the spontaneous IPSC frequency by approximately 30-55%. The miniature IPSCs (mIPSCs) seen in TTX-containing solutions had a frequency of approximately 10 Hz and an average conductance of 0.42-0.48 nS. 6. The kinetic properties of mIPSCs generated in pyramidal cells of different layers were the same, with the rise times of approximately 0.9 ms and decay time constants of approximately 8 ms at a holding potential of 0 mV. The decay phase of mIPSCs was generally fitted by one exponential and displayed a voltage dependence with an e-fold increase in decay time constant for a every 198-mV depolarization. 7. These results show that there is ongoing spontaneous release of GABA in neocortical slices that gives rise to high-frequency impulse-related and non-impulse-related postsynaptic inhibitory currents. Activation of AMPA receptors on inhibitory interneurons accounts for only a small proportion of the GABAA receptor-mediated events. Judging from the distribution of mIPSC frequencies in neurons of different laminae, there is a relatively uniform distribution of inhibitory synapses throughout the cortex. Tonic activation of GABAA receptors on neocortical pyramidal neurons generates an increase in resting membrane conductance that may play an important role in vivo by preventing the development of hyperexcitability, modulating excitatory synaptic events, and controlling the rate and patterns of spike discharge.

Inhibitory processes of hippocampal CA1 pyramidal neurons following kindling-induced epilepsy in the rat

1985 ◽  
Vol 63 (7) ◽  
pp. 872-878 ◽  
Author(s):  
M. W. Oliver ◽  
J. J. Miller
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Repetitive Stimulation ◽  
Membrane Properties ◽  
Stratum Radiatum ◽  
Inhibitory Processes ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Stimulation Of

To determine the alterations in cellular function which may contribute to the chronic predisposition of neuronal tissue to epileptiform activity, the membrane properties and inhibitory processes of hippocampal CA1 pyramidal cells were investigated using in vitro slices prepared from commissural-kindled rats. No changes were observed in resting membrane potential, input resistance, spike amplitude, and membrane time constant of "kindled" CA1 pyramidal neurons when compared with controls. There were also no differences between control and kindled preparations in the amplitude of recurrent inhibitory postsynaptic potentials (IPSP) and in the duration of inhibition produced by either alvear (Alv) or stratum radiatum (SR) stimulation. Irrespective of group, repetitive stimulation of the Alv reduced the amplitude of the recurrent IPSP but failed to induce seizurelike activity. On the other hand, repetitive stimulation of SR frequently produced a neuronal burst discharge even though the duration and to some extent the amplitude of orthodromic inhibition was increased. On the basis of these data, it may be suggested that chronic changes in CA1 pyramidal cell membrane properties and transient reductions of inhibitory processes do not underlie the enhanced sensitivity of these neurons to seizure activity associated with kindling.

Inhibitory control of excitable dendrites in neocortex

1995 ◽  
Vol 74 (4) ◽  
pp. 1810-1814 ◽  
Author(s):  
H. G. Kim ◽  
M. Beierlein ◽  
B. W. Connors
Keyword(s):  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Type I ◽  
Relative Timing ◽  
Inhibitory Postsynaptic Potentials ◽  
Glutamate Receptor Antagonists ◽  
Apical Dendrites ◽  
Whole Cell Recordings ◽  
Reversal Potentials ◽  
Stimulation Of

1. Many dendrites of pyramidal cells in mature neocortex express active Na+ and Ca2+ conductances. Dendrites are also the target of numerous inhibitory synapses. We examined the interactions between the intrinsic excitability of dendrites and synaptic inhibition using whole cell recordings from the apical dendrites of layer 5 pyramidal cells. Experiments were performed on slices of somatosensory cortex from mature rats. Slices were bathed in the glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6,7-dinitroquinoxaline-2,3-dione, and maintained at 32-36 degrees C. 2. In agreement with previous findings, intradendritic current injection evoked two distinct types of dendritic firing. Type I dendrites generated monophasic fast spikes, whereas type II dendrites showed more complex firing patterns, consisting of fast and slow spike components. 3. Stimulation of cortical layers 2/3 evoked fast inhibitory postsynaptic potentials (IPSPs) in all dendrites tested. IPSP reversal potentials were bimodally distributed, with means of about -53 and -85 mV when recorded with high-Cl(-)-concentration-filled electrodes. Interestingly, IPSP reversal potentials were correlated with the type of dendritic spiking pattern. 4. IPSPs were able to delay, completely block, or partially block spiking in dendrites, depending on the relative timing between inhibition and dendritic spiking. Slow, Ca(2+)-dependent spike components could be blocked selectively by IPSPs. Furthermore, inhibition could either phase advance or phase delay repetitive patterns of dendritic spiking, depending on the timing of the IPSP.

Effects of low concentrations of 4-aminopyridine on CA1 pyramidal cells of the hippocampus

1989 ◽  
Vol 61 (5) ◽  
pp. 953-970 ◽  
Author(s):  
P. Perreault ◽  
M. Avoli
Keyword(s):  
High Frequency ◽  
Hippocampal Slices ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Peak Latency ◽  
Excitatory Postsynaptic Potential ◽  
Average Value ◽  
Bath Application

1. Intracellular and extracellular recording techniques were used to study the effects of bath application of 4-aminopyridine (4-AP) on pyramidal cells of the CA1 subfield of rat hippocampal slices maintained in vitro. The concentration of 4-AP used in most experiments was 50 microM. However, similar results were obtained with a concentration ranging from 5 to 100 microM. 2. Following 4-AP application, cells impaled with K-acetate-filled microelectrodes hyperpolarized by an average of 2.6 mV (from -68.7 to -71.3 mV, P less than or equal to 0.01). This change was accompanied by the appearance of high-frequency spontaneous hyperpolarizations. Conversely, when KCl-filled microelectrodes were used, an average depolarization of 5.8 mV [from -73.1 to -67.3 mV, not significant (NS)] associated with the occurrence of repetitive depolarizing potentials was observed. In both cases, these changes were concomitant with a small decrease in membrane input resistance, which was statistically significant only for cells impaled with K-acetate-filled microelectrodes. When synaptic transmission was blocked by tetrodotoxin (TTX), 4-AP induced in cells studied with K-acetate microelectrodes an average depolarization of 2.4 mV (from -62.8 to -60.4 mV, P less than or equal to 0.01) accompanied by a small increase in input resistance (from 32.0 to 35.8 M omega, P less than or equal to 0.05). High-frequency spontaneous potentials failed to occur under these conditions. During 4-AP application, the threshold and the latency of action potentials elicited by a depolarizing current pulse increased in 36% of the neurons studied (n = 14). 3. The amplitude of the stratum (s.) radiatum-induced excitatory postsynaptic potential (EPSP) was augmented by 4-AP. Both the early and late inhibitory postsynaptic potentials (IPSPs) evoked by orthodromic stimuli were also increased in amplitude and duration. In addition, a late (peak latency, 150-600 ms) and long-lasting (duration, 600-1,500 ms) depolarizing potential appeared between the early and the late IPSPs and progressively increased until it partially masked these hyperpolarizations. This long-lasting depolarization (LLD) could also be induced by antidromic stimulation, although in this case it was preceded by an additional, fast-rising, brief depolarization. 4. A similar brief depolarization preceded the orthodromically induced LLD in 69% of the neurons bathed in the presence of 4-AP. The average value of the peak latency of this potential was 62 +/- 27 (SD) ms for orthodromic and 110 +/- 70 ms for antidromic responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Blocking GABAA Inhibition Reveals AMPA- and NMDA-Receptor-Mediated Polysynaptic Responses in the CA1 Region of the Rat Hippocampus

1997 ◽  
Vol 77 (4) ◽  
pp. 2071-2082 ◽  
Author(s):  
V. Crépel ◽  
R. Khazipov ◽  
Y. Ben-Ari
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Pyramidal Cell ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
External Concentration ◽  
Physiological Concentration ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Stimulation Of

Crépel, V., R. Khazipov, and Y. Ben-Ari. Blocking GABAA inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus. J. Neurophysiol. 77: 2071–2082, 1997. We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 μM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 μM), glycine (10 μM), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-d-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 μM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50–150 μm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline (10 μM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of d-2-amino-5-phosphonovalerate (50 μM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of γ-aminobutyric acid-A inhibition reveals glutamate receptor-mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.

Electric Low-Frequency Stimulation of the Tongue Induces Long-Term Depression of the Jaw-Opening Reflex in Anesthetized Mice

2004 ◽  
Vol 92 (6) ◽  
pp. 3332-3337 ◽  
Author(s):  
Jens Ellrich
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Conditioning Stimulation ◽  
Low Frequency Stimulation ◽  
Jaw Opening ◽  
Jaw Opening Reflex ◽  
Frequency Stimulation ◽  
Stimulation Of

Long-term depression (LTD) of somatosensory processing has been demonstrated in slice preparations of the spinal dorsal horn. Although LTD could be reliably induced in vitro, inconsistent results were encountered when the same types of experiments were conducted in adult animals in vivo. We addressed the hypothesis that LTD of orofacial sensorimotor processing can be induced in mice under general anesthesia. The effects of electric low- and high-frequency conditioning stimulation of the tongue on the sensorimotor jaw-opening reflex (JOR) elicited by electric tongue stimulation were investigated. Low-frequency stimulation induced a sustained decrease of the reflex integral for ≥1 h after the end of conditioning stimulation. After additional high-frequency stimulation, the reflex partly recovered from LTD. High-frequency stimulation alone induced a transient increase of the JOR integral for <10 min. The LTD of the sensorimotor jaw-opening reflex in anesthetized mice may be an appropriate model to investigate the central mechanisms and the pharmacology of synaptic plasticity in the orofacial region. The application of electrophysiological techniques in mice provides the opportunity to include adequate knock-out models to elucidate the neurobiology of LTD.

Low-threshold Ca2+ channels mediate induction of long-term potentiation in kitten visual cortex

1992 ◽  
Vol 67 (2) ◽  
pp. 401-410 ◽  
Author(s):  
Y. Komatsu ◽  
M. Iwakiri
Keyword(s):  
Visual Cortex ◽  
White Matter ◽  
Long Term Potentiation ◽  
Conditioning Stimulation ◽  
Term Potentiation ◽  
Bath Application ◽  
Low Threshold ◽  
Ca2 Channels ◽  
Stimulation Of

1. The induction mechanism of long-term potentiation (LTP) in developing visual cortex was studied by recording intracellular responses from layer III-IV cells in slice preparations of kitten visual cortex at 30-40 days after birth. 2. Strong stimulation of white matter produced a late depolarizing response after an orthodromic action potential. This depolarizing response was abolished by membrane depolarization or hyperpolarization caused by current injection through the recording electrode. In addition, this response was reduced by bath application of a low concentration (100 microM) of Ni2+ without any changes in the rising slope of the excitatory postsynaptic potential (EPSP) or orthodromic action potential. This suggests that this response is mediated by low-threshold Ca2+ channels (LTCs). 3. The involvement of LTCs in the induction of LTP was tested. White matter was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes in EPSPs were tested by low-frequency (0.1 Hz) stimulation of white matter. Conditioning stimulation produced a large N-methyl-D-aspartate (NMDA) receptor-mediated depolarizing response in these cells, which obscured the presence of the late depoliarzation. Therefore the test was conducted in a solution containing an NMDA antagonist 2-amino-5-phosphonovalerate (APV). 4. Weak conditioning stimulation, which evoked no LTC responses, never induced LTP; whereas strong conditioning stimulation, which evoked LTC responses, always induced LTP. Strong conditioning stimulation failed to induce LTP when LTC responses were prevented either by membrane depolarization or hyperpolarization or by a bath application of 100 microM Ni2+. 5. In a solution without APV, the application of Ni2+ also prevented the induction of LTP. 6. When cells were impaled by an electrode containing a Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), LTP was never induced, even though LTC responses were evoked by conditioning stimulation. These results indicate that Ca2+ influx into postsynaptic cells through LTCs induces the LTP. 7. The responses mediated by LTCs, which were evoked by the injection of current pulses into the cells, were maximum at the critical period of visual cortical plasticity, suggesting that LTCs in postsynaptic cells regulate the plastic changes in developing visual cortex.

Brain-Derived Neurotrophic Factor (BDNF) Modulates Inhibitory, But Not Excitatory, Transmission in the CA1 Region of the Hippocampus

1998 ◽  
Vol 80 (6) ◽  
pp. 3383-3386 ◽  
Author(s):  
M. Frerking ◽  
R. C. Malenka ◽  
R. A. Nicoll
Keyword(s):  
Neurotrophic Factor ◽  
Kinase Inhibitor ◽  
Pyramidal Cells ◽  
Brain Derived Neurotrophic Factor ◽  
Stratum Radiatum ◽  
Detectable Effect ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Presynaptic Site ◽  
Bath Application

Frerking, M., R. C. Malenka, and R. A. Nicoll. Brain-derived neurotrophic factor (BDNF) modulates inhibitory, but not excitatory, transmission in the CA1 region of the hippocampus. J. Neurophysiol. 80: 3383–3386, 1998. Brain-derived neurotrophic factor (BDNF) has been reported to have rapid effects on synaptic transmission in the hippocampus. We report here that bath application of BDNF causes a small but significant decrease in stimulus-evoked inhibitory postsynaptic currents (IPSCs) on CA1 pyramidal cells, which is prevented by the tyrosine kinase inhibitor lavendustin A. BDNF causes a decrease in the 1/CV2 of the IPSC, and also reduces paired-pulse depression of the IPSC, suggesting a presynaptic site of action. In contrast, BDNF did not have a detectable effect on field excitatory postsynaptic potentials measured in stratum radiatum. We conclude that BDNF has a selective depressant action on inhibitory transmission in the hippocampus, due at least in part to a presynaptic mechanism.

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