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At least 595 records · Page 33Linked to original sources
PubMed1994

Glycine-gated Cl- channels underlying synaptic currents.

Glycine receptor Cl- channels underlying inhibitory synaptic currents (IPSCs) were characterized with patch clamp methods applied to thin slices of rat spinal cord. The channels had multiple conductance states with their mean open time being similar to the mean decay time constant of IPSCs. During postnatal development, channel open time became gradually shorter, concomitantly with the decay time of IPSCs. Single channel currents of alpha-homomeric glycine receptors expressed in Xenopus oocytes from cRNAs showed that the adult type receptor had much faster kinetics than the fetal one. It is suggested that the molecular switching of glycine receptor alpha subunits accelerate the time course of inhibitory synaptic responses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Changes in hippocampal circuitry after pilocarpine-induced seizures as revealed by opioid receptor distribution and activation.

The pilocarpine model of temporal lobe epilepsy was used to study the time-dependent changes in dentate gyrus circuitry after seizures. Seizures caused a decrease in mu- and delta-opioid receptor immunoreactive (MOR-IR and DOR-IR, respectively) neurons in the hilus and MOR-IR neurons in the granule cell layer. Additionally, diffuse DOR-IR, MOR-IR, and GABA immunoreactivities (GABA-IR) were increased in the inner molecular layer. Using the in vitro hippocampal slice preparation to study the physiological consequences of the anatomical changes, we found that the disinhibitory effects of the mu-opioid receptor agonist [D-Ala2, MePhe4,Gly-(ol)5]-enkephalin (DAMGO) and the GABAA receptor antagonist bicuculline were greatly depressed 5-13 d after pilocarpine injection but returned to control levels within 6 weeks. The amplitudes of monosynaptic evoked IPSCs and the effects of DAMGO on this parameter were also slightly decreased 5-13 d after pilocarpine injection but significantly increased at 6 weeks. DAMGO significantly decreased the mean amplitude of spontaneous IPSCs (sIPSCs) at 6 weeks after pilocarpine injection but not in controls. The delta-opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE) principally inhibited excitatory transmission in saline-treated animals without affecting either sIPSCs or evoked IPSCs. The DPDPE-induced inhibition of excitatory transmission became more pronounced at 6 weeks after pilocarpine injection. These results illustrate the anatomical reorganization and functional changes in dentate gyrus circuitry evident in an animal model of temporal lobe epilepsy and provide evidence of compensatory changes after trauma to the hippocampal formation.

Animals↗
PubMed1997

N-ethylmaleimide blocks depolarization-induced suppression of inhibition and enhances GABA release in the rat hippocampal slice in vitro.

Regulation of synaptic, GABAA receptor-mediated inhibition is a process of critical importance to normal brain function. Recently, we have described a phenomenon in hippocampus of a transient, yet marked, decrease in spontaneous, GABAA receptor-mediated IPSCs after depolarization activated Ca2+ influx into a pyramidal cell. This process, depolarization-induced suppression of inhibition (DSI), is absent in hippocampal cells that previously had been exposed to pertussis toxin in vivo, implicating a G-protein in the DSI process. To circumvent the problem that a single cell cannot be studied before and after G-protein block using the pertussis toxin pretreatment method, we have used the sulfhydryl alkylating agent N-ethylmaleimide (NEM), which blocks pertussis toxin-sensitive G-proteins, to determine whether acute inhibition of G-proteins can eliminate DSI of spontaneous IPSCs (sIPSCs). In whole-cell recordings from CA1 pyramidal cells that were first determined to express DSI, we have found that NEM does block DSI of sIPSCs. We also report that DSI of monosynaptic, evoked IPSCs is blocked by NEM, suggesting that a similar mechanism underlies both forms of DSI. It was of interest that DSI was abolished at a time when NEM had increased, not decreased, GABA transmission. Indeed, NEM greatly increased quantal GABA release by a Ca(2+)-independent mechanism, an observation with potentially important implications for understanding synaptic GABA release.

Analysis of Variance↗
PubMed1998

A developmental shift from GABAergic to glycinergic transmission in the central auditory system.

GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine.

Aging↗
PubMed1998

Increased opioid inhibition of GABA release in nucleus accumbens during morphine withdrawal.

The nucleus accumbens is a key component of the reward pathway that plays a role in addiction to many drugs of abuse, including psychostimulants and opioids. The effects of withdrawal from chronic morphine were examined in the nucleus accumbens using brain slices from morphine-treated animals. Recordings were made from interneurons in the shell of nucleus accumbens, and the presynaptic inhibition of GABA-A IPSCs by opioids was examined. In slices from control animals, opioids caused a maximal inhibition of 50%, forskolin increased the IPSC amplitude by less than twofold, and the maximal inhibition by opioids in the presence of forskolin was not changed. During withdrawal, however, forskolin caused approximately a fourfold increase in the amplitude of the IPSC, and the maximal inhibition by opioids was increased to 80%. The results indicate that transmitter release is increased during opioid withdrawal, particularly after the activation of adenylyl cyclase. The cAMP-dependent increase in transmitter release is potently inhibited by opioids, such that the overall effect of opioids is augmented during withdrawal. The induction of an opioid-sensitive cAMP-dependent mechanism that regulates transmitter release may be a critical component of acute opioid withdrawal.

Adenylyl Cyclases↗
PubMed2026

From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.

Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).

Humans↗
PubMed2026

Establishment and characterization of two human pluripotent stem cell lines from patients with ATX-FGF14/spinocerebellar ataxia 27A (SCA27A).

Spinocerebellar ataxia 27A (SCA27A) is a rare inherited ataxia arising from heterozygous pathogenic loss-of-function variants in FGF14. Autosomal recessive FGF14-related cerebellar ataxia has also been reported in a single individual to date. Here, we describe the generation and characterization of human induced pluripotent stem cell (iPSC) lines derived from two individuals with FGF14-related ataxia (ATX-FGF14): one with SCA27A and one with autosomal recessive disease. Given the predominantly neuronal expression of FGF14, these iPSC lines represent a valuable resource for investigating the cellular and molecular consequences of FGF14 deficiency in disease-relevant neuronal populations following directed differentiation.

Humans↗
PubMed2026

Establishment and characterization of three human pluripotent stem cell lines from patients with spinocerebellar ataxia 27B (SCA27B).

Spinocerebellar ataxia 27B (SCA27B) is a common autosomal dominant cerebellar ataxia caused by an intronic GAA•TTC repeat expansion in the FGF14 gene. Here, we report the generation and validation of three human induced pluripotent stem cell (iPSC) lines derived from unrelated individuals with SCA27B, including two lines carrying a monoallelic pathogenic GAA•TTC repeat expansion in FGF14 and one line with biallelic expansions. These iPSC lines constitute a valuable resource, particularly given the predominantly neuronal expression of FGF14, and enable the investigation of disease mechanisms in relevant cell types following neuronal differentiation.

Humans↗
PubMed2026

Establishment of human induced pluripotent stem cell lines and isogenic gene-corrected controls from three patients with prolidase deficiency.

Prolidase deficiency is an autosomal recessive inborn error of metabolism caused by pathogenic variants in the PEPD gene. To date, close to 200 patients have been reported worldwide with a poorly understood pathomechanism. The PEPD gene encodes an enzyme that is involved in the final steps of collagen degradation. Urine amino acid analysis or specific dipeptide analysis can establish the biochemical diagnosis. In this study, we reprogrammed peripheral blood mononuclear cells (PBMCs) from three prolidase deficient patients into induced pluripotent stem cell (iPSC) lines and additionally generated isogenic controls using CRISPR-Cas9 genome editing. The pathogenic PEPD variants identified in our patients were NP_000276.2:p.? (NIHTVBi032-A), NP_000276.2:p.(Ile415Asn)/NP_000276.2:p.(Trp326Ter) (NIHTVBi033-A), and NP_000276.2:p.(Arg265Ter) (NIHTVBi034-A). These iPSC lines are valuable models to help investigate the pathomechanism of prolidase deficiency.

Humans↗
PubMed2026

Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.

The pathological hallmarks of neurodegeneration are the aberrant post-translational modification and aggregation of proteins. Genetic factors, like APOE4, increase the prevalence and severity of tau, amyloid, and α-synuclein pathologies. However, the human brain is largely inaccessible during this process, limiting mechanistic understanding. Here, we developed an iPSC-based 3D model that integrates neurons, glia, myelin, and cerebrovascular cells into a human brain-like tissue ("miBrain"). Single-nucleus RNA sequencing of miBrains confirmed the presence of diverse cell populations and revealed transcriptional responses to α-synuclein pathology. Like the human brain, pathogenic α-synuclein is increased in APOE4/4 miBrains. Combinatorial experiments revealed that endolysosomal dysfunction caused by cholesterol accumulation in APOE4/4 astrocytes impairs the degradation of soluble α-synuclein leading to a pathogenic transformation that seeds α-synuclein inclusions in neurons. Collectively, this study establishes a robust model for investigating protein inclusions in human iPSC-derived brain tissue and highlights the role of astrocytes and cholesterol in APOE4-mediated pathologies.

alpha-Synuclein↗
PubMed2026

Loss of function of the chromatin remodeling gene INO80D leads to neurogenic features of schizophrenia.

Schizophrenia has been linked to severely damaging de novo mutations in synaptic junction proteins, neurotransmitter receptors, transcription factors, and chromatin remodeling proteins. In a patient with schizophrenia in the absence of a family history of severe mental illness, we identified de novo nonsense mutation, INO80D p.Q568X, associated with both a truncated protein and partial nonsense-mediated decay. Three experiments were undertaken to evaluate the consequences of the mutation. 1) In neural stem cells (iNSCs) differentiated from WTC11 iPSCs, CRISPRi knockdown of INO80D led to downregulation of three subunits of the AMPA-glutamate receptor, of multiple genes mutant in schizophrenia, and of genes of synaptic function. 2) INO80D p.Q568X iNSCs and neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) had significantly lower expression of neurogenesis genes compared to patient-derived cells with the mutation corrected by CRISPR-Cas9 gene editing. Patient-derived INO80D p.Q568X neurons had significantly higher expression of cell division genes compared to lines with the mutation corrected, consistent with the possibility that some of these cells may be undergoing mitosis, which is not normal for neurons. 3) Finally, on microelectrode array (MEA) plates, WTC11-derived glutamatergic neurons with reduced expression of INO80D had more rapid firing rate and increased average network burst duration, both features of neurons derived from patients with neurodevelopmental disorders. Overall, these findings suggest that partial loss of INO80D function due to de novo mutation may have disrupted normal neurodevelopment and contributed to the schizophrenia of this patient.

Humans↗
PubMed1996

Depletion of glucose causes presynaptic inhibition of neuronal transmission in the rat dorsolateral septal nucleus.

The role of glucose in synaptic transmission was examined in the rat dorsolateral septal nucleus (DLSN) with single-microelectrode voltage-clamp and slice-patch technique. Removal of glucose from the oxygenated Krebs solution caused an outward current associated with an increased membrane conductance. The current-voltage relationship (I-V curve) showed that the hypoglycemia-induced outward current was reversed in polarity at the equilibrium potential for K+. Exposure of DLSN neurons to the glucose-free solution for 5-20 min depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC), and the late hyperpolarizing current (LHC). Replacement of glucose with 2-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the deprivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibitors of glucose metabolism, also depressed the PSCs, even in the presence of 10 mM glucose. Glucose-free perfusion did not significantly depress the glutamate-induced inward current, indicating that the inhibition of the EPSC by the glucose-free perfusion was presynaptic. gamma-Aminobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a patch-pipette solution containing 5 mM ATP attenuated the hypoglycemia-induced outward current. Glucose-free superfusion consistently inhibited the IPSC and the LHC without changing the GABA-induced outward current in ATP-treated DLSN neurons. It is suggested that glucose metabolism directly regulates the release of both excitatory amino acids and GABA from the presynaptic nerve terminals.

Animals↗
PubMed1998

Enantioselective modulation of GABAergic synaptic transmission by steroids and benz[e]indenes in hippocampal microcultures.

The effects of enantiomers of the neurosteroid analogues, 3alpha-hydroxy-5alpha-pregnan-20-one (DHP) and 3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile (ACN), and the benz[e]indene, BI-1, on synaptic currents were examined in microcultures of rat hippocampal neurons. Over the range of 0.1-10 microM, the (+)-enantiomers were more potent and effective than their (-)-enantiomeric counterparts in enhancing gamma-aminobutyric acid (GABA)A receptor-mediated evoked synaptic currents. The (+)-enantiomers had small effects on peak currents, but slowed the decay of inhibitory synaptic currents, resulting in 2-3-fold increases in charge transfer during inhibitory synaptic events at 10 microM. Similar prolongations of spontaneous miniature inhibitory postsynaptic currents (IPSCs) and responses to brief GABA pulses to outside-out patches suggest that the prolongations of evoked synaptic currents result primarily from postsynaptic effects. In contrast, the (-)-enantiomers had little effect on evoked IPSCs at concentrations < or = 1 microM, but enhanced inhibitory transmission at 10 microM. At concentrations < or = 1 microM, neither the (+)- nor (-)-enantiomers altered glutamate-mediated excitatory synaptic currents. At 10 microM, (+)-DHP and (+)-ACN depressed excitatory responses in a bicuculline-sensitive fashion, suggesting that direct chloride channel gating by the steroids contributed to the depression. These data indicate that certain steroids and benz[e]indenes augment inhibitory synaptic transmission enantioselectively and provide strong support for the hypothesis that steroids act at specific sites on synaptic GABA(A) receptors rather than via alteration of membrane lipids.

Androstanols↗
PubMed1999

Benzodiazepine tolerance at GABAergic synapses on hippocampal CA1 pyramidal cells.

Modulation of GABA function following 1 week oral administration of flurazepam (FZP) was investigated in chloride-loaded, rat hippocampal CA1 pyramidal neurons. Rats were sacrificed 2 or 7 days after ending drug treatment, when anticonvulsant tolerance was present or absent in vivo, respectively. Spontaneous (s)IPSCs and miniature (m)IPSCs were recorded using whole-cell voltage-clamp techniques. s/mIPSCs were bicuculline-sensitive, voltage-dependent, and reversed their polarity at 0 mV, the predicted E(Cl-). Comparisons of s/mIPSCs between FZP-treated and control groups were made at Vh = -90, -70, and -50 mV. The frequency of sIPSCs, but not mIPSCs, was significantly decreased in FZP-treated neurons 2 days, but not 7 days, after FZP treatment, suggesting a decrease in interneuron activity. These conclusions were supported by the negative findings of additional studies of [3H]GABA release from hippocampal slices and [3H]GABA uptake from hippocampal synaptosomes. The lack of change in the paired-pulse depression of GABA(B)-mediated IPSPs suggested that autoreceptor function was also not impaired following chronic FZP treatment. A large reduction in both sIPSC and mIPSC amplitude (60%) in FZP-treated neurons, the absence of mIPSCs in one-third of FZP-treated cells, and a measurable reduction in synaptic and unitary conductance confirmed that postsynaptic GABA(A) receptor function was profoundly impaired in FZP-treated CA1 neurons. Zolpidem, an alpha1-selective benzodiazepine receptor ligand, enhanced mIPSC amplitude and decay, but its ability to prolong mIPSC decay was reduced in FZP-treated neurons. Several pre- and postsynaptic changes at GABAergic synapses on CA1 pyramidal cells might be related to the decreased tonic GABA inhibition in FZP-treated CA1 neurons associated with the expression of benzodiazepine anticonvulsant tolerance.

Animals↗
PubMed2000

Differential effects of the group II mGluR agonist, DCG-IV, on depolarization-induced suppression of inhibition in hippocampal CA1 and CA3 neurons.

We investigated the role of metabotropic glutamate receptors in the mediation of depolarization-induced suppression of inhibition (DSI), using whole-cell electrophysiological techniques in rat hippocampal slice preparation. In a previous work, we showed that a retrograde signal travels from CA1 pyramidal cells to GABA interneurons and prevents them from releasing GABA for tens of seconds at 30 degrees C. The resulting suppression of inhibition is DSI. The retrograde signal appeared to be glutamate, or a glutamate analog, which acted on group I metabotropic receptors on the interneurons. It is not known if DSI occurs in hippocampal subregions besides CA1. If DSI does occur in other regions, it will be important to know if the role of metabotropic glutamate receptors (mGluRs) in mediating DSI is the same everywhere. The distribution of mGluR subtypes varies among hippocampal subregions. In the CA3 region, unlike CA1, group II mGluRs are prevalent. It was possible, therefore, that in CA3, the group II mGluRs would mediate DSI. We have begun to investigate these issues. We now report that: 1) DSI does occur in CA3. 2) Carbachol induces IPSC activity that can be recorded in CA1 and CA3a. This carbachol-induced activity can be reduced by the selective group II mGluR agonist, DCG-IV, and by DSI. 3) Evoked IPSCs in CA3a, but not in CA1, can be reduced by DCG-IV; hence the interneurons activated by carbachol may reside in CA3a. 4) Despite the group II mGluR agonist sensitivity of CA3a interneurons, DSI in this region is not affected by a group II mGluR antagonist, CPPG, and therefore does not appear to be mediated by group II mGluRs.

Animals↗
PubMed2003

Different actions of gabapentin and baclofen in hippocampus from weaver mice.

The pre- and postsynaptic effects of baclofen, a broad-spectrum gamma-aminobutyric acid (GABA)B receptor agonist, and gabapentin, a selective agonist at GABA(B) receptors composed of GABA(B)(1a,2) heterodimers, were examined in CA1 pyramidal cells using whole-cell patch-clamp recordings in hippocampal slices from different strains of mice. In slices from C57BL/6 mice, by means of GABA(B) receptors, gabapentin and baclofen activated outward K+ currents at resting membrane potential. In weaver mice with a Kir3.2 channel mutation, baclofen and gabapentin failed to activate postsynaptic K+ currents. However, in littermate controls of weaver mice, gabapentin failed to evoke K+ currents, whereas baclofen activated currents in the same cells. Thus, postsynaptic actions of gabapentin and baclofen on K+ currents are different in this mouse strain. Via presynaptic GABA(B) receptors, baclofen significantly reduced GABA(A) inhibitory postsynaptic currents (IPSCs) in slices from C57BL/6 mice, as well as weaver and control mice. In contrast, gabapentin did not affect IPSCs significantly in any group of mice. These results indicate that although baclofen and gabapentin are agonists at postsynaptic GABA(B) receptors positively coupled to K+ channels, their mechanism of action differs in certain strains of mice, including the weaver wild-type mice, suggesting a dissociation in their signaling mechanism and coupling to K+ channels.

Acetates↗
PubMed2004

Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse.

The growth factor neuregulin 1 (NRG1) has been proposed to contribute to the formation and maturation of neuromuscular and interneuronal synapses by upregulating the expression of specific neurotransmitter receptor subunits. In the present report, we show that, in the hippocampus, NRG1 is expressed in a pattern suggesting that it regulates synapse development in the CA1 region. However, in contrast to what has been shown in other synapses, NRG1 reduces the expression of gamma-aminobutyric acid (GABA)A receptors alpha subunits in hippocampal slices, and the mean amplitude of GABAergic miniature inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons, without affecting IPSC kinetics or frequency. These effects of NRG1 occur without concomitant changes in glutamate receptors and other synaptic proteins. We propose that the role of NRG1 in the formation and maturation in the hippocampal inhibitory synapse is downregulation, rather than upregulation, of receptor subunit expression. These results suggest that NRG1 may contribute to the reduction in GABAergic synaptic activity in hippocampal CA1 pyramidal neurons that normally occurs during early postnatal development, and that alterations in NRG1 signaling in the hippocampus may contribute to schizophrenia and epilepsy.

Animals↗
PubMed2005

Fundamental differences in spontaneous synaptic inhibition between deep and superficial layers of the rat entorhinal cortex.

We have previously shown that there are clear differences between spontaneous excitatory synaptic currents recorded in layers V and II of the rat entorhinal cortex (EC) in vitro, and have suggested that these might contribute to a more pronounced susceptibility of the deeper layer to epileptogenesis. In the present study, we have made a detailed comparison of spontaneous synaptic inhibition between the two layers by recording spontaneous inhibitory synaptic currents (sIPSCs) using whole-cell patch-clamp techniques in EC slices. Pharmacological studies indicated that sIPSCs were mediated exclusively by gamma-aminobutyric acid (GABA)(A) receptors. There was little difference in average amplitudes, rise or decay times of sIPSCs in layer II compared with layer V. However, in the former, events occurred at 4-5 times the frequency seen in the latter, and frequencies of </=40 Hz were not uncommon. When activity-independent, miniature IPSCs were isolated in tetrodotoxin (TTX), the frequency in layer V was more than halved, but in layer II only a small reduction was seen, and the frequency remained very high. In terms of kinetics, while averaged sIPSCs in each layer were very similar, detailed comparison of individual sIPSCs within layers revealed distinct differences, possibly reflecting inputs from different subtypes of interneurons or inputs at different somatodendritic locations. In layer V, sIPSCs could be divided into three groups, one with slow rise and decay kinetics and a second with fast rise kinetics, further distinguished into two groups by either fast or slow decay kinetics. The distinction between events in layer II was simpler, one group having both fast rise and decay times and the second with both parameters much slower. Finally, IPSCs could occur in high-frequency bursts in both layers, although these were much more prevalent in layer II. The results are discussed in terms of the overall level of background inhibition in the two layers, as well as how this might relate to their susceptibilities to epileptogenesis.

Anesthetics, Local↗