Search results for "Postsynaptic potential"
showing 10 items of 371 documents
Disruption of otoferlin alters the mode of exocytosis at the mouse inner hair cell ribbon synapse
2019
Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C-2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from f…
Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model
2020
Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes we…
Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model
2018
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…
Coincident Activation of Glutamate Receptors Enhances GABAA Receptor-Induced Ionic Plasticity of the Intracellular Cl−-Concentration in Dissociated N…
2019
Massive activation of γ-amino butyric acid A (GABAA) receptors during pathophysiological activity induces an increase in the intracellular Cl−-concentration ([Cl−]i), which is sufficient to render GABAergic responses excitatory. However, to what extent physiological levels of GABAergic activity can influence [Cl−]i is not known. Aim of the present study is to reveal whether moderate activation of GABAA receptors mediates functionally relevant [Cl−]i changes and whether these changes can be augmented by coincident glutamatergic activity. To address these questions, we used whole-cell patch-clamp recordings from cultured cortical neurons [at days in vitro (DIV) 6–22] to determine changes in t…
Nitric oxide/cGMP signaling via guanylyl cyclase isoform 1 modulates glutamate and GABA release in somatosensory cortex of mice
2017
Abstract In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input–output curves of evoked signa…
The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae
2015
AbstractChanges in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinforma…
Cortical network mechanisms of response inhibition
2020
SummaryBoth the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA) are crucial for successful response inhibition. However, the particular functional roles of those two regions have been controversially debated for more than a decade now. It is unclear whether the rIFG directly initiates stopping or serves an attentional function, whereas the stopping is triggered by the pre-SMA. The current multimodal MEG/fMRI study sought to clarify the role and temporal activation order of both regions in response inhibition using a selective stopping task. This task dissociates inhibitory from attentional processes. Our results reliably reveal a temporal precedence of rIF…
Focal Cortical Lesions Induce Bidirectional Changes in the Excitability of Fast Spiking and Non Fast Spiking Cortical Interneurons
2014
A physiological brain function requires neuronal networks to operate within a well-defined range of activity. Indeed, alterations in neuronal excitability have been associated with several pathological conditions, ranging from epilepsy to neuropsychiatric disorders. Changes in inhibitory transmission are known to play a key role in the development of hyperexcitability. However it is largely unknown whether specific interneuronal subpopulations contribute differentially to such pathological condition. In the present study we investigated functional alterations of inhibitory interneurons embedded in a hyperexcitable cortical circuit at the border of chronically induced focal lesions in mouse …
Semilunar Granule Cells Are the Primary Source of the Perisomatic Excitatory Innervation onto Parvalbumin-Expressing Interneurons in the Dentate Gyrus
2020
AbstractWe analyzed the origin and relevance of the perisomatic excitatory inputs on the parvalbumin interneurons of the granule cell layer in mouse. Confocal analysis of the glutamatergic innervation showed that it represents ∼50% of the perisomatic synapses that parvalbumin cells receive. This excitatory input may originate from granule cell collaterals, the mossy cells, or even supramammillary nucleus. First, we assessed the input from the mossy cells on parvalbumin interneurons. Axon terminals of mossy cells were visualized by their calretinin content. Using multicolor confocal microscopy, we observed that less than 10% of perisomatic excitatory innervation of parvalbumin cells could or…
The relation between neuronal chloride transporter activities, GABA inhibition, and neuronal activity
2020
Abstract The intracellular chloride concentration [Cl−]i in neurons is regulated by a set of transmembrane transporters, with the Cl−-loader NKCC1 and the Cl−-extruder KCC2 as most relevant members. The expression of these transporters is tightly regulated, with the general trend that KCC2 expression is low in immature neurons, which are thus characterized by a high [Cl−]i. As [Cl−]i is the main factor determining the polarity of GABAergic responses, such a high [Cl−]i is related to depolarizing GABAergic responses. However, depolarizing GABAergic responses are not per se excitatory, but can also contribute to shunting inhibition. The excitatory/inhibitory action of GABAergic responses is m…