Excitatory synapse

Résumé

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell. This phenomenon is known as an excitatory postsynaptic potential (EPSP). It may occur via direct contact between cells (i.e., via gap junctions), as in an electrical synapse, but most commonly occurs via the vesicular release of neurotransmitters from the presynaptic axon terminal into the synaptic cleft, as in a chemical synapse. The excitatory neurotransmitters, the most common of which is glutamate, then migrate v

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Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in the hippocampal CA3 circuit

Mickael Maurice Zbili

Homeostatic plasticity of intrinsic excitability goes hand in hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging, and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2 to 3 d induces an up-regulation of both synaptic transmission at CA3-CA3 connections and intrinsic excitability of CA3 pyramidal neurons. Intrinsic plasticity was found to be mediated by a reduction of Kv1.1 channel density at the axon initial segment. In activity-deprived circuits, CA3-CA3 synapses were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a reduction in presynaptic Kv1.1 function. Further support for the down-regulation of axonal Kv1.1 channels in activity-deprived neurons was the broadening of action potentials measured in the axon. We conclude that regulation of the axonal Kv1.1 channel constitutes a major mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.

NATL ACAD SCIENCES2021

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In the brainstem auditory circuit of mammals and birds, excitatory synapses with extraordinarily large size have evolved, which ensure fast membrane potential signaling mediated by large, multiquantal excitatory postsynaptic currents (EPSCs). The so-called "calyx of Held" synapses are formed by the globular bushy cells (GBCs) in the ventral cochlear nucleus (VCN) onto the contralateral medial nucleus of the trapezoid body (MNTB) neurons. One the other hand, the spherical bushy cells (SBCs) in the VCN project to the lateral superior olive (LSO), where they form small bouton-like synapses. Therefore, the lower auditory brainstem circuits constitute an example of synapse-specificity, in which presynaptic neuron pools are connected through highly specific synapses to their postsynaptic partner neurons. Calyx of Held synapses are formed at postnatal day 2 - 4 in rodents in a target-cell specific manner and prior to the onset of hearing. The molecular signaling pathways which drive the formation of these synapses are unknown. Here we identify bone morphogenetic protein (BMP) signaling as an essential signaling pathway in the development of calyces of Held. Through unbiased genome-wide transcriptome analyses in rats and mice, BMPs were identified as candidates for diffusible signaling molecules which are expressed at a higher level in the MNTB (the target area of calyces of Held), as compared to the LSO. The microarray analysis was validated by quantitative PCR (qPCR) and in-situ hybridisation. A conditional knock-out (KO) of BMP-receptor 1a (BMPR1a) in the lower auditory system, in the genetic background of a conventional KO of BMP-receptor 1b (BMPR1b), was then used to address the role of BMP-receptor signaling for calyx of Held formation in vivo. Genetically knocking out BMPR1a/1b activity in the auditory brainstem led to a drastic deficit at the calyx of Held synapses both morphologically and functionally, as well as to the persistence of multiple innervation of MNTB neurons. This study therefore shows that BMP signaling drives the development of the large calyx of Held synapses. The study offers a possible mechanism for the specificity of a large excitatory synapse formation in the central nervous systems (CNS). In addition, the study shows a novel function of BMP signaling in synaptogenesis in the mammalian CNS.

EPFL2011

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A subpopulation of cortical VIP-expressing interneurons with highly dynamic spines

Jérôme Blanc, Christina Georgiou, Graham Knott, Kok Sin Lee

Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the structural plasticity of inhibitory neurons remains limited. Interneurons are divided into various subclasses, each with specialized functions in cortical circuits. Further knowledge of subclass-specific structural plasticity of interneurons is crucial to gaining a complete mechanistic understanding of their contribution to cortical plasticity overall. Here, we describe a subpopulation of superficial cortical multipolar interneurons expressing vasoactive intestinal peptide (VIP) with high spine densities on their dendrites located in layer (L) 1, and with the electrophysiological characteristics of bursting cells. Using longitudinal imaging in vivo, we found that the majority of the spines are highly dynamic, displaying lifetimes considerably shorter than that of spines on pyramidal neurons. Using correlative light and electron microscopy, we confirmed that these VIP spines are sites of excitatory synaptic contacts, and are morphologically distinct from other spines in L1. Advanced light and electron microscopy identify a subset of cortical multipolar vasoactive intestinal peptide interneurons with high spine dynamics and characteristics that are greatly different from pyramidal neurons.

NATURE PORTFOLIO2022

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