Temporal Patterns and Depolarizing Actions of Spontaneous GABAA Receptor Activation in Granule Cells of the Early Postnatal Dentate Gyrus

1998 ◽  
Vol 80 (5) ◽  
pp. 2340-2351 ◽  
Author(s):  
Greg S. Hollrigel ◽  
Stephen T. Ross ◽  
Ivan Soltesz
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Temporal Patterns ◽  
Receptor Activation ◽  
Disulfonic Acid ◽  
Whole Cell ◽  
Postsynaptic Currents

Hollrigel, Greg S., Stephen T. Ross, and Ivan Soltesz. Temporal patterns and depolarizing actions of spontaneous GABAA receptor activation in granule cells of the early postnatal dentate gyrus. J. Neurophysiol. 80: 2340–2351, 1998. Whole cell patch-clamp recordings were used to investigate the properties of the γ-aminobutyric acid type A (GABAA) receptor-mediated spontaneous synaptic events in immature granule cells of the developing, early postnatal day (P0–P6) rat dentate gyrus. With Cs-gluconate-filled whole cell patch pipettes at 0 mV in control medium, spontaneous inhibitory postsynaptic currents (sIPSCs) occurred in prominent bursts (peak amplitude of the bursts 406.9 ± 58.4 pA; intraburst IPSC frequency 71.0 ± 12.4 Hz) at 0.05 ± 0.02 Hz in every immature granule cell younger than P7. Between the bursts of IPSCs, lower frequency (1.7 ± 0.7 Hz), interburst IPSCs could be observed. Bicuculline and picrotoxin as well as the intracellularly applied chloride-channel blockers CsF− and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) abolished the intraburst as well as the interburst IPSCs, indicating that the IPSCs were mediated by GABAA receptor channels. The bursts of IPSCs, but not the interburst IPSCs, were blocked by the simultaneous application of the glutamate receptor antagonists 2-amino-5-phosphovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating the importance of the glutamatergic excitatory drive onto the interneurons in the early postnatal dentate gyrus. The spontaneously occurring excitatory postsynaptic currents in immature granule cells, observable after the intracellular blockade of GABAA receptor channels with CsF− and DIDS, appeared exclusively as single events at low frequencies, i.e., they did not occur in prominent bursts. Gramicidin-based perforated patch-clamp recordings determined that the reversal potential for the burst of IPSCs (−46.6 ± 3.1 mV) was more depolarized than the resting membrane potential (−54.2 ± 4.2 mV) but more hyperpolarized than the action potential threshold (−41.8 ± 1.7 mV). The depolarizing action of the bursts of synaptic events most often evoked only a single action potential per burst. Simultaneous whole cell patch recordings, with KCl-filled patch pipettes at −60 mV in current clamp from pairs of immature granule cells of the developing dentate gyrus, determined that the bursts of IPSPs took place in a similar temporal pattern but with imperfect synchrony in neighboring granule cells (average lag between the onsets of the bursts between granule cell pairs 77.7 ± 8.6 ms). These results show that the spontaneous activation of GABAA receptors in immature dentate granule cells displays unique properties that are distinct from the temporal patterns and biophysical features of spontaneous GABAA receptor activation taking place in the developing Ammon's horn and in the adult dentate gyrus.

Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings

1992 ◽  
Vol 67 (5) ◽  
pp. 1346-1358 ◽  
Author(s):  
K. J. Staley ◽  
T. S. Otis ◽  
I. Mody
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Membrane Voltage ◽  
Membrane Properties ◽  
Whole Cell ◽  
Calcium Buffers ◽  
Whole Cell Recordings

1. Whole-cell and sharp electrode recordings from adult rat dentate gyrus GCs were performed in the 400-microns-thick hippocampal slice preparation maintained at 34 +/- 1 degrees C. Intrinsic membrane properties of granule cells (GCs) were evaluated with the use of a switching current-clamp amplifier. 2. With the whole-cell technique, the average resting membrane potential (RMP) of GCs was -85 mV when a potassium gluconate electrode solution was used versus -74 mV measured with potassium acetate-filled sharp microelectrodes. The membrane voltage response to injected current was linear over two membrane potential ranges, greater than 10 mV hyperpolarized from RMP and between 10 mV more negative than RMP and -62 mV. The average input resistances (RN) calculated over these ranges were 107 and 228 M omega in the whole-cell recordings versus 37 and 54 M omega in the sharp electrode recordings. There was no correlation between RMP and RN with either recording technique. The membrane time constant (tau m) determined at the RMP was 26.9 ms for whole-cell recordings and 13.9 ms for sharp electrode recordings. 3. There was no evidence of time-dependent changes in RMP, RN, and tau m in whole-cell recordings, although the slow inward rectification seen at hyperpolarized potentials decreased over 30-60 min. Addition of calcium buffers to the whole-cell recording solution did not result in a significant change in the average RMP, the average RN, or the average tau m. 4. Action potential threshold was comparable in whole-cell (-49 mV) and sharp electrode (-52 mV) recordings, but action potential amplitude was larger in whole-cell (126 mV) than in sharp electrode (106 mV) recordings. Spike frequency adaptation was present in the whole-cell recordings and could be abolished by addition of calcium buffers to the electrode solution. 5. We estimated rho, the ratio of dendritic to somatic conductance, to be 5.1 for the whole-cell records and 2.1 for sharp electrode recordings. The electrotonic length of the equivalent cylinder representing the cell processes was estimated to be 0.49 from the whole-cell data and 0.79 from the sharp electrode recordings. This implies that at rest there is only a 10% decrement in steady-state membrane voltage along the length of the dendrite due to shunting across the membrane resistance; small synaptic events occurring in the distal dendritic tree will therefore have a more substantial influence on the soma than previous analyses suggested.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution and functional properties of 5-HT3 receptors in the rat hippocampal dentate gyrus: a patch-clamp study

1994 ◽  
Vol 71 (5) ◽  
pp. 1935-1947 ◽  
Author(s):  
K. Kawa
Keyword(s):  
Patch Clamp ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Receptor Subtype ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Inward Current ◽  
Basket Cells ◽  
Inward Currents ◽  
Induced Currents

1. In dentate gyrus of rat hippocampal slices two distinct types of neurons, principal excitatory neurons (granule cells) and local inhibitory neurons (basket cells), could be identified under Nomarski microscopy; I investigated the actions of serotonin using the whole-cell patch-clamp technique. The identification of the neurons was later confirmed by intracellular staining with Lucifer yellow. 2. In both basket cells and granule cells, whole-cell current recordings revealed spontaneous synaptic currents ranging from < 10 pA to > 200 pA in symmetrical Cl- conditions at a holding potential of -63 mV. These currents were blocked by 10 microM bicuculline, indicating that they resulted from the spontaneous activation of GABAergic inputs (which had been morphologically described in both types of neurons). 3. By focal application of serotonin (2–50 microM) to basket cells under current clamp I evoked a train of action potentials superimposed on a baseline membrane depolarization. Under voltage-clamp conditions serotonin evoked an inward current at a holding potential of -63 mV (currents were detectable in approximately 90% of basket cells studied). The inward current was accompanied by a multitude of small inward currents of short duration (< 100 ms) that were found to be due to the stimulation by serotonin of nearby GABAergic presynaptic neurons innervating the recorded neuron. 4. In granule cells (total of 11 cells) serotonin did not produce any responses under conditions similar to those used for basket cells. The occurrence of bicuculline-sensitive spontaneous synaptic current events seemed to increase during the application of serotonin; this phenomenon reflected the excitatory action of serotonin exclusively on GABAergic interneurons. 5. The serotonin-induced inward currents in basket cells were mediated by the 5-HT3 receptor subtype because 1) they were blocked by either metoclopramide (10 microM) or [3-alpha-tropanyl]-1H-indolecarboxylic acid ester (2 nM), the latter being a specific blocker for the 5-HT3 receptor subtype, and 2) almost similar currents were induced by the application of the selective 5-HT3 receptor agonist 2-methyl 5-HT (2–50 microM) or 1-(m-chlorophenyl)-biguanide (0.1–10 microM). 6. Current-voltage (I–V) relations of serotonin-induced currents in basket cells showed that the reversal potential was close to 0 mV in external standard saline and depended on the concentrations of monovalent cations. I–V relations of serotonin-induced currents revealed inward rectification at the membrane potential range of +30 to -60 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

2020 ◽  
Vol 123 (2) ◽  
pp. 755-772 ◽  
Author(s):  
Poonam Mishra ◽  
Rishikesh Narayanan
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Temporal Summation ◽  
Granule Cells ◽  
Intrinsic Excitability ◽  
Frequency Dependent ◽  
Response Properties ◽  
Whole Cell Patch Clamp ◽  
Afferent Information

The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest region, and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns, and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies and voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly fewer action potentials compared with those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing. NEW & NOTEWORTHY We employed whole cell patch-clamp recordings from granule cells in the three subregions of the rat dentate gyrus to demonstrate considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, granule cells did not express membrane potential resonance, and their impedance profiles lacked inductive phase leads at all measured frequencies. Our analyses also show that granule cells manifest class I excitability characteristics, categorizing them as integrators of afferent information.

The chemokine SDF1 regulates migration of dentate granule cells

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4249-4260 ◽  
Author(s):  
Anil Bagri ◽  
Theresa Gurney ◽  
Xiaoping He ◽  
Yong-Rui Zou ◽  
Dan R. Littman ◽  
...  
Keyword(s):  
Cell Migration ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Ectopic Expression ◽  
Dentate Granule Cell ◽  
Vitro Assay ◽  
Dentate Granule Cells ◽  
Cell Position

The dentate gyrus is the primary afferent pathway into the hippocampus, but there is little information concerning the molecular influences that govern its formation. In particular, the control of migration and cell positioning of dentate granule cells is not clear. We have characterized more fully the timing and route of granule cell migration during embryogenesis using in utero retroviral injections. Using this information, we developed an in vitro assay that faithfully recapitulates important events in dentate gyrus morphogenesis. In searching for candidate ligands that may regulate dentate granule cell migration, we found that SDF1, a chemokine that regulates cerebellar and leukocyte migration, and its receptor CXCR4 are expressed in patterns that suggest a role in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect in granule cell position. Ectopic expression of SDF1 in our explant assay showed that it directly regulates dentate granule cell migration. Our study shows that a chemokine is necessary for the normal development of the dentate gyrus, a forebrain structure crucial for learning and memory.

Mossy Fiber–Granule Cell Synapses in the Normal and Epileptic Rat Dentate Gyrus Studied With Minimal Laser Photostimulation

1999 ◽  
Vol 82 (4) ◽  
pp. 1883-1894 ◽  
Author(s):  
Péter Molnár ◽  
J. Victor Nadler
Keyword(s):  
Status Epilepticus ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Hippocampal Formation ◽  
Control Groups ◽  
Small Component ◽  
Fiber Growth ◽  
And Control

Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy fiber–granule cell synapses is difficult to characterize unambiguously, because electrical stimulation may activate other pathways and because there is a low probability of granule cell interconnection. These problems were addressed by the use of scanning laser photostimulation in slices of the caudal hippocampal formation. Glutamate was released from a caged precursor with highly focused ultraviolet light to evoke action potentials in a small population of granule cells. Excitatory synaptic currents were recorded in the presence of bicuculline. Minimal laser photostimulation evoked an apparently unitary excitatory postsynaptic current (EPSC) in 61% of granule cells from rats that had experienced pilocarpine-induced status epilepticus followed by recurrent mossy fiber growth. An EPSC was also evoked in 13–16% of granule cells from the control groups. EPSCs from status epilepticus and control groups had similar peak amplitudes (∼30 pA), 20–80% rise times (∼1.2 ms), decay time constants (∼10 ms), and half-widths (∼8 ms). The mean failure rate was high (∼70%) in both groups, and in both groups activation of N-methyl-d-aspartate receptors contributed a small component to the EPSC. The strong similarity between responses from the status epilepticus and control groups suggests that they resulted from activation of a similar synaptic population. No EPSC was recorded when the laser beam was focused in the dentate hilus, suggesting that indirect activation of hilar mossy cells contributed little, if at all, to these results. Recurrent mossy fiber growth increases the density of mossy fiber–granule cell synapses in the caudal dentate gyrus by perhaps sixfold, but the new synapses appear to operate very similarly to preexisting mossy fiber–granule cell synapses.

NMDA-Dependent Currents in Granule Cells of the Dentate Gyrus Contribute to Induction but Not Permanence of Kindling

1999 ◽  
Vol 81 (2) ◽  
pp. 564-574 ◽  
Author(s):  
Ümit Sayin ◽  
Paul Rutecki ◽  
Thomas Sutula
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Time Course ◽  
Granule Cells ◽  
Receptor Activation ◽  
Perforant Path ◽  
Synaptic Current ◽  
Synaptic Currents ◽  
Class V ◽  
Dependent Component

NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling. Single-electrode voltage-clamp techniques and bath application of the N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30–35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor–dependent component of the perforant path–evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path–evoked current was increased by 63–111% at a holding potential of −30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5–3 mo after the last of 3 or 90–120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control values during a time course of 2.5–3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor–dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling.

scholarly journals NMDA Receptor-Dependent Plasticity of Granule Cell Spiking in the Dentate Gyrus of Normal and Epileptic Rats

2000 ◽  
Vol 84 (6) ◽  
pp. 2868-2879 ◽  
Author(s):  
M. Lynch ◽  
Ü. Sayin ◽  
G. Golarai ◽  
T. Sutula
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Perforant Path ◽  
Spike Generation ◽  
Bathing Medium ◽  
Burst Discharge ◽  
Dependent Component ◽  
Single Spike

Because granule cells in the dentate gyrus provide a major synaptic input to pyramidal neurons in the CA3 region of the hippocampus, spike generation by granule cells is likely to have a significant role in hippocampal information processing. Granule cells normally fire in a single-spike mode even when inhibition is blocked and provide single-spike output to CA3 when afferent activity converging into the entorhinal cortex from neocortex, brainstem, and other limbic regions increases. The effects of enhancement of N-methyl-d-aspartate (NMDA) receptor-dependent excitatory synaptic transmission and reduction in γ-aminobutyric acid-A (GABAA) receptor-dependent inhibition on spike generation were examined in granule cells of the dentate gyrus. In contrast to the single-spike mode observed in normal bathing conditions, perforant path stimulation in Mg2+-free bathing conditions evoked graded burst discharges in granule cells which increased in duration, amplitude, and number of spikes as a function of stimulus intensity. After burst discharges were evoked during transient exposure to bathing conditions that relieve the Mg2+ block of the NMDA receptor, there was a marked increase in the NMDA receptor-dependent component of the EPSP, but no significant increase in the non-NMDA receptor-dependent component of the EPSP in normal bathing medium. Supramaximal perforant path stimulation still evoked only a single spike, but granule cell spike generation was immediately converted from a single-spike firing mode to a graded burst discharge mode when inhibition was then reduced. The induction of graded burst discharges in Mg2+-free conditions and the expression of burst discharges evoked in normal bathing medium with subsequent disinhibition were both blocked bydl-2-amino-4-phosphonovaleric acid (APV) and were therefore NMDA receptor dependent, in contrast to long-term potentiation (LTP) in the perforant path, which is induced by NMDA receptors and is also expressed by α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptors. The graded burst discharge mode was also observed in granule cells when inhibition was reduced after a single epileptic afterdischarge, which enhances the NMDA receptor-dependent component of evoked synaptic response, and in the dentate gyrus reorganized by mossy fiber sprouting in kindled and kainic acid-treated rats. NMDA receptor-dependent plasticity of granule cell spike generation, which can be distinguished from LTP and induces long-term susceptibility to epileptic burst discharge under conditions of reduced inhibition, could modify information processing in the hippocampus and promote epileptic synchronization by increasing excitatory input into CA3.

Optical Recording Study of Granule Cell Activities in the Hippocampal Dentate Gyrus of Kainate-Treated Rats

2000 ◽  
Vol 83 (4) ◽  
pp. 2421-2430 ◽  
Author(s):  
Yo Otsu ◽  
Eiichi Maru ◽  
Hisayuki Ohata ◽  
Ichiro Takashima ◽  
Riichi Kajiwara ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Mossy Fibers ◽  
Optical Recording ◽  
Granule Cell Layer ◽  
Gabaergic Inhibition ◽  
Mossy Fiber Sprouting

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca2+. The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizurelike activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.

scholarly journals Propagation of Action Potentials From the Soma to Individual Dendrite of Cultured Rat Amacrine Cells Is Regulated by Local GABA Input

2002 ◽  
Vol 87 (6) ◽  
pp. 2858-2866 ◽  
Author(s):  
Yoshitake Yamada ◽  
Amane Koizumi ◽  
Eisuke Iwasaki ◽  
Shu-Ichi Watanabe ◽  
Akimichi Kaneko
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Lateral Inhibition ◽  
Action Potentials ◽  
Amacrine Cell ◽  
Amacrine Cells ◽  
Inner Plexiform Layer ◽  
Whole Cell ◽  
Cell Patch Clamp ◽  
Whole Cell Patch Clamp

Retinal amacrine cells are interneurons that make lateral and vertical connections in the inner plexiform layer of the retina. Amacrine cells do not possess a long axon, and this morphological feature is the origin of their naming. Their dendrites function as both presynaptic and postsynaptic sites. Half of all amacrine cells are GABAergic inhibitory neurons that mediate lateral inhibition, and their light-evoked response consists of graded voltage changes and regenerative action potentials. There is evidence that the amount of neurotransmitter release from presynaptic sites is increased by spike propagation into the dendrite. Thus understanding of how action potentials propagate in dendrites is important to elucidating the extent and strength of lateral inhibition. In the present study, we used the dual whole cell patch-clamp technique on the soma and the dendrite of cultured rat amacrine cells and directly demonstrated that the action potentials propagate into the dendrites. The action potential in the dendrite was TTX sensitive and was affected by the local membrane potential of the dendrite. Propagation of the action potential was suppressed by local application of GABA to the dendrite. Dual dendrite whole cell patch-clamp recordings showed that GABA suppresses the propagation of action potentials in one dendrite of an amacrine cell, while the action potentials propagate in the other dendrites. It is likely that the action potentials in the dendrites are susceptible to various external factors resulting in the nonuniform propagation of the action potential from the soma of an amacrine cell.

scholarly journals Enhanced Tonic GABA Current in Normotopic and Hilar Ectopic Dentate Granule Cells After Pilocarpine-Induced Status Epilepticus

2009 ◽  
Vol 102 (2) ◽  
pp. 670-681 ◽  
Author(s):  
Ren-Zhi Zhan ◽  
J. Victor Nadler
Keyword(s):  
Plasma Membrane ◽  
Status Epilepticus ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Membrane Transport ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Gaba Concentration ◽  
Dentate Granule Cells ◽  
Gaba Inhibition

In temporal lobe epilepsy, loss of inhibitory neurons and circuit changes in the dentate gyrus promote hyperexcitability. This hyperexcitability is compensated to the point that dentate granule cells exhibit normal or even subnormal excitability under some conditions. This study explored the possibility that compensation involves enhanced tonic GABA inhibition. Whole cell patch-clamp recordings were made from normotopic granule cells in hippocampal slices from control rats and from both normotopic and hilar ectopic granule cells in slices from rats subjected to pilocarpine-induced status epilepticus. After status epilepticus, tonic GABA current was an order of magnitude greater than control in normotopic granule cells and was significantly greater in hilar ectopic than in normotopic granule cells. These differences could be observed whether or not the extracellular GABA concentration was increased by adding GABA to the superfusion medium or blocking plasma membrane transport. The enhanced tonic GABA current had both action potential–dependent and action potential–independent components. Pharmacological studies suggested that the small tonic GABA current of granule cells in control rats was mediated largely by high-affinity α4βxδ GABAA receptors but that the much larger current recorded after status epilepticus was mediated largely by the lower-affinity α5βxγ2 GABAA receptors. A large α5βxγ2-mediated tonic current could be recorded from controls only when the extracellular GABA concentration was increased. Status epilepticus seemed not to impair the control of extracellular GABA concentration by plasma membrane transport substantially. Upregulated tonic GABA inhibition may account for the unexpectedly modest excitability of the dentate gyrus in epileptic brain.

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