Inhibitory postsynaptic potential

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. IPSPs were first investigated in motorneurons by David P. C. Lloyd, John Eccles and Rodolfo Llinás in the 1950s and 1960s. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell to cell signalling. Inhibitory presynaptic neurons release neurotransmitters that then bind to the postsynaptic receptors; this induces a change in the permeability of the postsynaptic neuronal membrane to particular ions. An electric current that changes the postsynaptic membrane potential to create a more negative postsynaptic potential is generated, i.e. the postsynaptic membrane potential becomes

Dendritic Voltage Recordings Explain Paradoxical Synaptic Plasticity: A Modeling Study

Wulfram Gerstner, Laureline Logiaco, Claire Meissner-Bernard, Matthias Chinyen Tsai

Experiments have shown that the same stimulation pattern that causes Long-Term Potentiation in proximal synapses, will induce Long-Term Depression in distal ones. In order to understand these, and other, surprising observations we use a phenomenological model of Hebbian plasticity at the location of the synapse. Our model describes the Hebbian condition of joint activity of pre- and postsynaptic neurons in a compact form as the interaction of the glutamate trace left by a presynaptic spike with the time course of the postsynaptic voltage. Instead of simulating the voltage, we test the model using experimentally recorded dendritic voltage traces in hippocampus and neocortex. We find that the time course of the voltage in the neighborhood of a stimulated synapse is a reliable predictor of whether a stimulated synapse undergoes potentiation, depression, or no change. Our computational model can explain the existence of different -at first glance seemingly paradoxical- outcomes of synaptic potentiation and depression experiments depending on the dendritic location of the synapse and the frequency or timing of the stimulation.

FRONTIERS RESEARCH FOUNDATION2020

Functional and structural properties of strong inhibitory synapses in a binaural auditory circuit

Enida Gjoni

Neuronal circuits are defined in their function and computational outcome by the synaptic interplay of Excitation and Inhibition (E/I). One step further in understanding the role of these opposite interactors in neuronal computations consists in determining their relative contribution, in terms of input strength and convergence. In the auditory brainstem, neurons in the Lateral Superior Olive (LSO) rely upon binaural E/I integration for computing sound-source localization. We made use of this circuit as a model for understanding the role of synaptic connectivity in information processing. We characterized the functional connectivity of the inhibitory and excitatory inputs onto a given LSO neuron. We found that LSO neurons receive few but large inhibitory inputs with a unitary conductance of 9 nS (under physiological intracellular Cl- concentration), although the unitary strength of inputs scattered over a 10-fold range. We estimated that unitary inhibitory postsynaptic currents (IPSCs) were mediated by a large number of synchronously released glycine vesicles (on average: 48 ± 39, range 9 - 115). The large quantal content suggests that these IPSCs are generated by a high number of functional release sites. Electron-microscopy based reconstructions revealed the structural specialization of the inhibitory axons which contacted the soma and proximal dendrites of a LSO neuron multiple times via large varicosities (diameter range 1 ¿ 11 µm), each containing on average three active zones. In contrast to the strong unitary IPSCs, excitatory inputs were numerous but had a small unitary conductance (~ 0.7 nS). A computational model of E/I integration showed that the strength and convergence of excitatory inputs determines how spontaneous firing is transmitted from upstream neurons, whereas the strength and convergence of inhibitory inputs determines the dynamic range of the tuning curve. We then aimed to study mechanisms underlying the developmental acquisition of strong inhibitory inputs on LSO neurons. Input-output curves were gradual at post-natal days (P) 5 and 6 but showed, in most cases, clear steps from P7 onwards, indicative of a reduction in the number of synaptic inputs and a growth in the strength of the individual inputs. In addition, we wished to investigate whether Synaptotagmin1 (Syt1) represents the Calcium sensor that guarantees the co-release of glutamate which has been known to occur at the immature inhibitory MNTB - LSO synapses. Genetic deletion of Syt1 caused asynchronous glutamate release only during the first 2 ¿ 3 post-natal days, suggesting that Syt1 might gradually become redundant with another Calcium sensor after ~ P5. In conclusion, this study highlights the functional and structural specializations of inhibitory synapses optimized for fulfilling the computational properties of binaural neurons devoted to sound localization. It also suggests that the basic synaptic connectivity at this connection is laid down in the first week of postnatal development.

EPFL2017

Cell-type-specific nicotinic input disinhibits mouse barrel cortex during active sensing

Sylvain Crochet, Célia Roxane Gasselin, Benoît Hohl, Carl Petersen

Fast synaptic transmission relies upon the activation of ionotropic receptors by neurotransmitter release to evoke postsynaptic potentials. Glutamate and GABA play dominant roles in driving highly dynamic activity in synaptically connected neuronal circuits, but ionotropic receptors for other neurotransmitters are also expressed in the neocortex, including nicotinic receptors, which are non-selective cation channels gated by acetylcholine. To study the function of non-glutamatergic excitation in neocortex, we used two-photon microscopy to target whole-cell membrane potential recordings to different types of genetically defined neurons in layer 2/3 of primary somatosensory barrel cortex in awake head-restrained mice combined with pharmacological and optogenetic manipulations. Here, we report a prominent nicotinic input, which selectively depolarizes a subtype of GABAergic neuron expressing vasoactive intestinal peptide leading to disinhibition during active sensorimotor processing. Nicotinic disinhibition of somatosensory cortex during active sensing might contribute importantly to integration of top-down and motor-related signals necessary for tactile perception and learning.

CELL PRESS2021

Functional and structural properties of strong inhibitory synapses in a binaural auditory circuit

Enida Gjoni

EPFL2017