Acute Injury to Superficial Cortex Leads to a Decrease in Synaptic Inhibition and Increase in Excitation in Neocortical Layer V Pyramidal Cells

2007 ◽  
Vol 97 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Lie Yang ◽  
Larry S. Benardo ◽  
Helen Valsamis ◽  
Douglas S. F. Ling
Keyword(s):  
Pyramidal Cells ◽  
Cell Voltage ◽  
Gaba Release ◽  
Acute Injury ◽  
Inhibitory Synapses ◽  
Fluctuation Analysis ◽  
Synaptic Excitation ◽  
The Mean ◽  
Layer V ◽  
Local Circuits

Injury to the superficial layers of cerebral cortex produces alterations in the synaptic responses of local circuits that promote the development of seizures. To further delineate the specific changes in synaptic strength that are induced by this type of cortical injury, whole cell voltage-clamp recordings were used to examine evoked and spontaneous synaptic events from layer V pyramidal cells in coronal slices prepared from surgically traumatized rat neocortices in which the superficial third of the cortex (layers I, II, and part of III) was removed. Slices from intact neocortices were used as controls. Examinations of fast inhibitory postsynaptic currents (IPSCs) indicated that traumatized slices were disinhibited, exhibiting evoked IPSCs (eIPSCs) with lower peak amplitudes. Measurements of spontaneous IPSCs (sIPSCs) revealed no difference in the mean amplitudes of sIPSCs recorded in traumatized versus control slices. However, the mean sIPSC frequency was lower in traumatized slices, indicative of a decrease in GABA release at these inhibitory synapses. Traumatized slices also displayed an increase in synaptic excitation, exhibiting spontaneous EPSCs (sESPCs) with larger peak amplitudes and higher frequencies. Peak-scaled nonstationary fluctuation analysis of sEPSCs and sIPSCs was used to obtain estimates of the unit conductance and number of functional receptor channels. EPSC and IPSC channel numbers and IPSC unit conductance did not differ between traumatized and intact slices. However, the mean unit conductance of EPSCs was higher (+25%) in traumatized slices. These findings suggest that acute injury to the superficial neocortical layers results in a disinhibition of cortical circuits that stems from a decline in GABA release likely due to the loss of superficial inhibitory interneurons and an enhancement of synaptic excitation consequent to an increase in the AMPA receptor unit conductance.

Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked

2005 ◽  
Vol 93 (5) ◽  
pp. 2656-2667 ◽  
Author(s):  
Joshua T. Kantrowitz ◽  
N. Noelle Francis ◽  
Alejandro Salah ◽  
Katherine L. Perkins
Keyword(s):  
Voltage Clamp ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Phosphinic Acid ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Gaba Release ◽  
Gabab Receptors ◽  
The Mean ◽  
Ca3 Pyramidal Cells

In the presence of 4-aminopyridine, interneurons fire synchronously, causing giant GABA-mediated postsynaptic potentials (GPSPs; GPSCs in voltage clamp) in CA3 pyramidal cells in hippocampal slices from adult guinea pigs. These triphasic GPSPs are composed of a GABAA-mediated hyperpolarizing component, a depolarizing component, and a GABAB-mediated hyperpolarizing component. We propose that GABAB receptors exert control over the postsynaptic depolarizing GABA response. Microelectrode and cell-attached recordings demonstrated that the mean number of action potentials during the depolarizing component of the GPSP increased dramatically in the presence of the GABAB receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2- hydroxypropyl](phenylmethyl) phosphinic acid (CGP 55845A; P = 0.003 and 0.0005, respectively). Whole cell voltage-clamp recordings showed that the postsynaptic GABAB and depolarizing GABA components of the GPSC overlap substantially, allowing the GABAB-mediated hyperpolarization to suppress the excitation mediated by the depolarizing GABA component. Further voltage-clamp recordings showed that CGP 55845A increased the duration of the depolarizing GABA component of the GPSC even when the GABAB component had already been blocked by internal QX-314, suggesting that CGP 55845A also increased the duration of GABA release. When glutamatergic transmission is intact, GPSPs directly precede epileptiform afterdischarges. We hypothesize that the depolarizing component of the GPSP triggers the epileptiform events and show here that enhancement of the depolarizing component with CGP 55845A increased epileptiform activity. CGP 55845A increased the likelihood of a GPSP triggering an epileptiform event from 32 to 99% ( P = 0.0000001), and significantly increased the number of afterdischarges per epileptiform event ( P = 0.001). Loss of GABAB receptor function is associated with temporal lobe epilepsy in rodents and humans. We show here that GABAB receptors exert control over the synaptic depolarizing GABA response and that block of GABAB receptors makes the depolarizing GABA response excitatory and proconvulsive.

Distinct Local Circuits Between Neocortical Pyramidal Cells and Fast-Spiking Interneurons in Young Adult Rats

2003 ◽  
Vol 89 (2) ◽  
pp. 943-953 ◽  
Author(s):  
María Cecilia Angulo ◽  
Jochen F. Staiger ◽  
Jean Rossier ◽  
Etienne Audinat
Keyword(s):  
Young Adult ◽  
Dendritic Tree ◽  
Release Site ◽  
Pyramidal Cells ◽  
Inhibitory Effect ◽  
Adult Rats ◽  
Release Probability ◽  
Fast Spiking ◽  
Layer V ◽  
Local Circuits

Connections between layer V pyramidal cells and GABAergic fast-spiking interneurons (pyramidal-FS) were studied by paired recordings combined with morphological analyses in acute neocortical slices from 28- to 52-day-old rats. Pairs of spikes elicited in pyramidal cells at a stimulation rate of 0.2 Hz induced unitary excitatory postsynaptic currents (EPSCs) in FS interneurons that displayed facilitation (48%), depression (38.5%), or neither depression nor facilitation (13.5%). Analyses of the EPSC amplitude distributions indicate that depressing connections always showed multiple functional release sites. On the contrary, facilitating connections consisted either of one or several release sites. At a holding potential of −72 mV, the quantal size ( q) and the release probability ( p) of facilitating connections with a single release site were –21.9 ± 7.5 pA and 0.49 ± 0.19 (SD), respectively. The mean q and the estimated number of release sites ( n) at connections showing multiple sites were obtained by decreasing the release probability and did not differ between depressing and facilitating synapses (depressing connections: q = –15.3 ± 2.5 pA, n = 5.1 ± 3, facilitating connections: q = –23.9 ± 9.8 pA, n = 7.8 ± 5.4). However, the quantal content at facilitating synapses with multiple sites (1.9 ± 1.5) was significantly different from that at depressing connections (4.1 ± 3.9). Finally, quantitative morphological analyses revealed that most of the pyramidal cells displaying facilitation can be differentiated from those displaying depression by a more densely branched apical dendritic tree. Therefore two types of morphologically distinct pyramidal cells form excitatory connections with FS interneurons that differ in their short-term plasticity characteristics. Facilitating and depressing connections may provide a differential control of the temporal information processing of FS cells and thus finely regulate the inhibitory effect of these interneurons in neocortical networks of young adult rats.

Kinetics of GABAB autoreceptor-mediated suppression of GABA release in rat insular cortex

2012 ◽  
Vol 107 (5) ◽  
pp. 1431-1442 ◽  
Author(s):  
Masayuki Kobayashi ◽  
Hiroki Takei ◽  
Kiyofumi Yamamoto ◽  
Hiroshige Hatanaka ◽  
Noriaki Koshikawa
Keyword(s):  
Insular Cortex ◽  
Pyramidal Cells ◽  
Gaba Release ◽  
Paired Pulse ◽  
Whole Cell Patch Clamp ◽  
Pulse Ratio ◽  
Presynaptic Mechanisms ◽  
Fast Spiking ◽  
Layer V ◽  
Interevent Interval

Release of GABA is controlled by presynaptic GABA receptor type B (GABAB) autoreceptors at GABAergic terminals. However, there is no direct evidence that GABAB autoreceptors are activated by GABA release from their own terminals, and precise profiles of GABAB autoreceptor-mediated suppression of GABA release remain unknown. To explore these issues, we performed multiple whole-cell, patch-clamp recordings from layer V rat insular cortex. Both unitary inhibitory and excitatory postsynaptic currents (uIPSCs and uEPSCs, respectively) were recorded by applying a five-train depolarizing pulse injection at 20 Hz. In connections from both fast-spiking (FS) and non-FS interneurons to pyramidal cells, the GABAB receptor antagonist CGP 52432 had little effect on the initial uIPSC amplitude. However, uIPSCs, responding to later pulses, were effectively facilitated. This CGP 52432-induced facilitation was prominent in the fourth uIPSCs, which were evoked 150 ms after the first uIPSC. The facilitation of uIPSCs was accompanied by an increase in the paired-pulse ratio. In addition, analysis of the coefficient of variation suggests the involvement of presynaptic mechanisms in CGP 52432-induced uIPSC facilitation. Paired-pulse stimulation (interstimulus interval = 150 ms) of presynaptic FS cells revealed that the second uIPSC was also facilitated by CGP 52432, which had little effect on the amplitude and interevent interval of miniature IPSCs. In contrast, uEPSCs, responding to all five stimulations of a presynaptic pyramidal cell, were less affected by CGP 52432. These results suggest that a single presynaptic action potential is sufficient to activate GABAB autoreceptors and to suppress GABA release in the cerebral cortex.

Restrictions on Inhibitory Circuits Contribute to Limited Recruitment of Fast Inhibition in Rat Neocortical Pyramidal Cells

1999 ◽  
Vol 82 (4) ◽  
pp. 1793-1807 ◽  
Author(s):  
Douglas S. F. Ling ◽  
Larry S. Benardo
Keyword(s):  
Noise Exposure ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Superficial Layer ◽  
Mean Value ◽  
Published Data ◽  
Inhibitory Circuits ◽  
Quantal Size ◽  
The Mean ◽  
Layer V

To further define the operational boundaries on fast inhibition in neocortex, whole cell recordings were made from layer V pyramidal neurons in neocortical slices to evaluate evoked inhibitory postsynaptic currents (IPSCs) and spontaneous miniature IPSCs (mIPSCs). Stimulating electrodes were placed in layers VI and I/II to determine whether simultaneous stimulation of deep and superficial laminae could extend the magnitude of maximal IPSCs evoked by deep-layer stimulation alone. The addition of superficial-layer stimulation did not increase maximal IPSC amplitude, confirming the strict limit on fast inhibition. Spontaneous miniature IPSCs were recorded in the presence of tetrodotoxin. The frequency of spontaneous mIPSCs ranged from 10.0 to 33.1 Hz. mIPSC amplitude varied considerably, with a range of 5.0–128.2 pA and a mean value of 20.7 ± 4.1 pA ( n = 12 cells). The decay phase of miniature IPSCs was best fit by a single exponential, similar to evoked IPSCs. The mean time constant of decay was 6.4 ± 0.6 ms, with a range of 0.2–20.1 ms. The mean 10–90% rise time was 1.9 ± 0.2 ms, ranging from 0.2 to 6.3 ms. Evaluation of mIPSC kinetics revealed no evidence of dendritic filtering. Amplitude histograms of mIPSCs exhibited skewed distributions with several discernable peaks that, when fit with Gaussian curves, appeared to be spaced equidistantly, suggesting that mIPSC amplitudes varied quantally. The mean separation of Gaussian peaks ranged from 6.1 to 7.8 pA. The quantal distributions did not appear to be artifacts of noise. Exposure to saline containing low Ca2+ and high Mg2+ concentrations reduced the number of histogram peaks, but did not affect the quantal size. Mean mIPSC amplitude and quantal size varied with cell holding potential in a near-linear manner. Statistical evaluation of amplitude histograms verified the multimodality of mIPSC amplitude distributions and corroborated the equidistant spacing of peaks. Comparison of mIPSC values with published data from single GABA channel recordings suggests that the mean mIPSC conductance corresponds to the activation of 10–20 GABAA receptor channels, and that the release of a single inhibitory quantum opens 3–6 channels. Further comparison of mIPSCs with evoked inhibitory events suggests that a single interneuron may form, on average, 4–12 functional synapses with a pyramidal cell, and that 10–12 individual interneurons are engaged during recruitment of maximal population IPSCs. This suggests that inhibitory circuits are much more restricted in both the size of the unit events and effective number of connections when compared with excitatory inputs.

GAT-3 Transporters Regulate Inhibition in the Neocortex

2005 ◽  
Vol 94 (6) ◽  
pp. 4533-4537 ◽  
Author(s):  
Gregory A. Kinney
Keyword(s):  
Pyramidal Cells ◽  
Gaba Release ◽  
Inhibitory Interneuron ◽  
Inhibitory Interneurons ◽  
Slice Preparation ◽  
Rat Neocortex ◽  
Ambient Gaba ◽  
Layer V

The role of GAT-3 transporters in regulating GABAA receptor-mediated inhibition was examined in the rat neocortex using an in vitro slice preparation. Pharmacologically isolated GABAA receptor-mediated responses were recorded from layer V neocortical pyramidal cells, and the effects of SNAP-5114, a GAT-3 GABA transporter-selective antagonist, were evaluated. Application of SNAP-5114 resulted in a reversible increase in the amplitude of an evoked GABAA response in most cells examined, although no effect on the decay time was observed. Examination of the spontaneous output of inhibitory interneurons revealed a reversible increase in the frequency and amplitude of spontaneous inhibitory synaptic currents as a consequence of GAT-3 inhibition. This effect of GAT-3 inhibition on spontaneous inhibitory events was action potential-dependent because no such increases were observed when SNAP-5114 was applied in the presence of TTX. These results demonstrate that GAT-3 transporters regulate inhibitory interneuron output in the neocortex. The increase in inhibitory interneuron excitability resulting from application of SNAP-5114 suggests that inhibition of GAT-3 transporter function results in a reduction in ambient GABA levels, possibly by a reduction in carrier-mediated GABA release via the GAT-3 transporter.

Presynaptic Interneuron Subtype- and Age-Dependent Modulation of GABAergic Synaptic Transmission by β-Adrenoceptors in Rat Insular Cortex

2010 ◽  
Vol 103 (5) ◽  
pp. 2876-2888 ◽  
Author(s):  
Yuko Koyanagi ◽  
Kiyofumi Yamamoto ◽  
Yoshiyuki Oi ◽  
Noriaki Koshikawa ◽  
Masayuki Kobayashi
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
Insular Cortex ◽  
Pyramidal Cells ◽  
Gaba Release ◽  
Taste Aversion Learning ◽  
Inhibitory Synaptic Transmission ◽  
Whole Cell Patch Clamp ◽  
Adrenergic Modulation ◽  
Layer V

β-Adrenoceptors play a crucial role in the regulation of taste aversion learning in the insular cortex (IC). However, β-adrenergic effects on inhibitory synaptic transmission mediated by γ-aminobutyric acid (GABA) remain unknown. To elucidate the mechanisms of β-adrenergic modulation of inhibitory synaptic transmission, we performed paired whole cell patch-clamp recordings from layer V GABAergic interneurons and pyramidal cells of rat IC aged from postnatal day 17 (PD17) to PD46 and examined the effects of isoproterenol, a β-adrenoceptor agonist, on unitary inhibitory postsynaptic currents (uIPSCs). Isoproterenol (100 μM) induced facilitating effects on uIPSCs in 33.3% of cell pairs accompanied by decreases in coefficient of variation (CV) of the first uIPSC amplitude and paired-pulse ratio (PPR) of the second to first uIPSC amplitude, whereas 35.9% of pairs showed suppressive effects of isoproterenol on uIPSC amplitude obtained from fast spiking (FS) to pyramidal cell pairs. Facilitatory effects of isoproterenol were frequently observed in FS–pyramidal cell pairs at ≥PD24. On the other hand, isoproterenol suppressed uIPSC amplitude by 52.3 and 39.8% in low-threshold spike (LTS)–pyramidal and late spiking (LS)–pyramidal cell pairs, respectively, with increases in CV and PPR. The isoproterenol-induced suppressive effects were blocked by preapplication of 100 μM propranolol, a β-adrenoceptor antagonist. There was no significant correlation between age and changes of uIPSCs in LTS–/LS–pyramidal cell pairs. These results suggest the presence of differential mechanisms in presynaptic GABA release and/or postsynaptic GABAA receptor-related assemblies among interneuron subtypes. Age- and interneuron subtype-specific β-adrenergic modulation of IPSCs may contribute to experience-dependent plasticity in the IC.

NPY Sensitivity and Postsynaptic Properties of Heterotopic Neurons in the MAM Model of Malformation-Associated Epilepsy

2002 ◽  
Vol 88 (5) ◽  
pp. 2745-2754 ◽  
Author(s):  
A. R. Pentney ◽  
S. C. Baraban ◽  
W. F. Colmers
Keyword(s):  
Epileptiform Activity ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Neurological Dysfunction ◽  
Inward Rectification ◽  
Small Contribution ◽  
Pregnant Rats ◽  
Synaptic Excitation ◽  
Layer 2 ◽  
Ca1 Cells

Neuronal migration disorders (NMDs) can be associated with neurological dysfunction such as mental retardation, and clusters of disorganized cells (heterotopias) often act as seizure foci in medically intractable partial epilepsies. Methylazoxymethanol (MAM) treatment of pregnant rats results in neuronal heterotopias in offspring, especially in hippocampal area CA1. Although the neurons in dysplastic areas in this model are frequently hyperexcitable, the precise mechanisms controlling excitability remain unclear. Here, we used IR-DIC videomicroscopy and whole cell voltage-clamp techniques to test whether the potent anti-excitatory actions of neuropeptide Y (NPY) affected synaptic excitation of heterotopic neurons. We also compared several synaptic and intrinsic properties of heterotopic, layer 2–3 cortical, and CA1 pyramidal neurons, to further characterize heterotopic cells. NPY powerfully inhibited synaptic excitation onto normal and normotopic CA1 cells but was nearly ineffective on responses evoked in heterotopic cells from stimulation sites within the heterotopia. Glutamatergic synaptic responses on heterotopic cells exhibited a comparatively small, d-2-amino-5-phosphopentanoic acid-sensitive, N-methyl-d-aspartate component. Heterotopic neurons also differed from normal CA1 cells in postsynaptic membrane currents, possessing a prominent inwardly rectifying K+ current sensitive to Cs+and Ba2+, similar to neocortical layer 2–3 pyramidal cells. CA1 cells instead had a prominent Cs+- and 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride-sensitive I h and negligible inward rectification, unlike heterotopic cells. Thus heterotopic CA1 cells appear to share numerous physiological similarities with neocortical neurons. The lack of NPY's effects on intra-heterotopic inputs, the small contribution of I h, and abnormal glutamate receptor function, may all contribute to the lowered threshold for epileptiform activity observed in hippocampal heterotopias and could be important factors in epilepsies associated with NMDs.

Stimulation of 5-HT2 Receptors in Prefrontal Pyramidal Neurons Inhibits Cav1.2 L-Type Ca2+Currents Via a PLCβ/IP3/Calcineurin Signaling Cascade

2002 ◽  
Vol 87 (5) ◽  
pp. 2490-2504 ◽  
Author(s):  
Michelle Day ◽  
Patricia A. Olson ◽  
Josef Platzer ◽  
Joerg Striessnig ◽  
D. James Surmeier
Keyword(s):  
Pyramidal Neurons ◽  
Inositol Trisphosphate ◽  
Cell Voltage ◽  
Signaling Cascade ◽  
Channel Modulation ◽  
Receptor Modulation ◽  
Bath Application ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Layer V

There is growing evidence linking alterations in serotonergic signaling in the prefrontal cortex to the etiology of schizophrenia. Prefrontal pyramidal neurons are richly innervated by serotonergic fibers and express high levels of serotonergic 5-HT2-class receptors. It is unclear, however, how activation of these receptors modulates cellular activity. To help fill this gap, whole cell voltage-clamp and single-cell RT-PCR studies of acutely isolated layer V–VI prefrontal pyramidal neurons were undertaken. The vast majority (>80%) of these neurons had detectable levels of 5-HT2A or 5-HT2C receptor mRNA. Bath application of 5-HT2 agonists inhibited voltage-dependent Ca2+ channel currents. L-type Ca2+ channels were a particularly prominent target of this signaling pathway. The L-type channel modulation was blocked by disruption of Gαq signaling or by inhibition of phospholipase Cβ. Antagonism of intracellular inositol trisphosphate signaling, chelation of intracellular Ca2+, or depletion of intracellular Ca2+ stores also blocked this modulation. Inhibition of the Ca2+-dependent phosphatase calcineurin prevented receptor-mediated modulation of L-type currents. Last, the 5-HT2 receptor modulation was robustly expressed in neurons from Cav1.3 knockout mice. These findings argue that 5-HT2receptors couple through Gαq proteins to trigger a phospholipase Cβ/inositol trisphosphate signaling cascade resulting in the mobilization of intracellular Ca2+, activation of calcineurin, and inhibition of Cav1.2 L-type Ca2+currents. This modulation and its blockade by atypical neuroleptics could have wide-ranging effects on synaptic integration and long-term gene expression in deep-layer prefrontal pyramidal neurons.

Properties of Unitary IPSCs in Hippocampal Pyramidal Cells Originating From Different Types of Interneurons in Young Rats

1997 ◽  
Vol 77 (4) ◽  
pp. 1939-1949 ◽  
Author(s):  
Mohamed Ouardouz ◽  
Jean-Claude Lacaille
Keyword(s):  
Reversal Potential ◽  
Pyramidal Cells ◽  
Mean Amplitude ◽  
Paired Pulse ◽  
Young Rats ◽  
Different Types ◽  
The Mean ◽  
Paired Pulse Depression ◽  
Types Of Interneurons ◽  
Stimulation Of

Ouardouz, Mohamed and Jean-Claude Lacaille. Properties of unitary IPSCs in hippocampal pyramidal cells originating from different types of interneurons in young rats. J. Neurophysiol. 77: 1939–1949, 1997. Whole cell recordings were used in hippocampal slices of young rats to examine unitary inhibitory postsynaptic currents (uIPSCs) evoked in CA1 pyramidal cells at room temperature. Loose cell-attached stimulation was applied to activate single interneurons of different subtypes located in stratum oriens (OR), near stratum pyramidale (PYR), and at the border of stratum radiatum and lacunosum-moleculare (LM). uIPSCs evoked by stimulation of PYR and OR interneurons had similar onset latency, rise time, peak amplitude, and decay. In contrast, uIPSCs elicited by activation of LM interneurons were significantly smaller in amplitude and had a slower time course. The mean reversal potential of uIPSCs was −53.1 ± 2.1 (SE) mV during recordings with intracellular solution containing potassium gluconate. With the use of recording solution containing the potassium channel blocker cesium, the reversal potential of uIPSCs was not significantly different (−58.5 ± 2.6 mV), suggesting that these synaptic currents were not mediated by potassium conductances. Bath application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (25 μM) reversibly blocked uIPSCs evoked by stimulation of all interneuron subtypes. In bicuculline, the mean peak amplitude of uIPSCs recorded with potassium gluconate was reduced to 3.5 ± 4.4% of control ( n = 7). Similarly, with cesium methanesulfonate, the mean amplitude in bicuculline was 2.9 ± 3.1% of control ( n = 13). Application of the GABAB receptor antagonist CGP 55845A (5 μM) resulted in a significant and reversible increase in the mean amplitude of uIPSCs recorded with cesium-containing intracellular solution. Thus uIPSCs from all cell types appeared under tonic presynaptic inhibition by GABAB receptors. Paired stimulation of individual interneurons at 100- to 200-ms intervals did not result in paired pulse depression of uIPSCs. For individual responses, a significant negative correlation was observed between the amplitude of the first and second uIPSCs. A significant paired pulse facilitation (154.0 ± 8.0%) was observed when the first uIPSC was smaller than the mean of all first uIPSCs. A small, but not significant, paired pulse depression (90.8 ± 4.0%) was found when the first uIPSC was larger than the mean of all first uIPSCs. Our results indicate that these different subtypes of hippocampal interneurons generate Cl−-mediated GABAA uIPSCs. uIPSCs originating from different types of interneurons may have heterogeneous properties and may be subject to tonic presynaptic inhibition via heterosynaptic GABAB receptors. These results suggest a specialization of function for inhibitory interneurons and point to complex presynaptic modulation of interneuron function.

scholarly journals GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

2018 ◽  
Vol 115 (51) ◽  
pp. E12083-E12090 ◽  
Author(s):  
Adam Bleckert ◽  
Chi Zhang ◽  
Maxwell H. Turner ◽  
David Koren ◽  
David M. Berson ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Selective Reduction ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Direction Selectivity ◽  
Inhibitory Synapses ◽  
Retinal Ganglion ◽  
Gabaergic Transmission ◽  
Starburst Amacrine Cells ◽  
Receptor Clusters

Synaptic inhibition controls a neuron’s output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on–off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC’s soma and dendrites could facilitate homeostatic control of the ooDSGC’s output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.

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