Homer‐1a/Vesl‐1S enhances hippocampal synaptic transmission

Abstract

Homer/Vesl proteins are involved in regulating metabotropic glutamate receptors, synaptogenesis, dendritic spine development and axonal pathfinding. We investigated the potential modulation of glutamatergic synaptic transmission by the immediate early gene product Homer-1a/Vesl-1S and by the constitutively expressed long-form Homer-1c/Vesl-1L in CA1 pyramidal cells from cultured rat hippocampal slices. Semliki Forest virus vector-mediated overexpression of Homer-1a enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, but did not detectably affect N-methyl-d-aspartate (NMDA) receptor function and presynaptic glutamate release. Overexpression of Homer-1c, by contrast, did not alter synaptic transmission. To corroborate our electrophysiological results obtained in slice cultures, we performed quantitative immunocytochemistry in cultures of dissociated hippocampal neurons. Homer-1a also increased synaptic clustering of AMPA but not NMDA receptors, whereas Homer-1c had no detectable effect. Our results show that Homer-1a potentiates synaptic AMPA receptor function, supporting a critical role for Homer-1a in hippocampal synaptic plasticity.

Homer/Vesl Proteins and Their Roles in CNS Neurons

“…We found that overexpression of Homer-1a enhanced AMPA receptor function and clustering, whereas it affected neither NMDA receptor function and clustering nor presynaptic glutamate release (53). In contrast to Homer-1a, Homer-1c overexpression did not alter synaptic transmission.…”

“…our previous study (53) that Homer-1a promotes AMPA receptor insertion at both functional synapses (containing AMPA and NMDA receptors) and previously silent synapses (expressing only NMDA receptors; Fig. 3).…”

Potential New Antiepileptogenic Targets Indicated by Microarray Analysis in a Rat Model for Temporal Lobe Epilepsy

“…NMDA receptor glutamatebinding chain (Grina) was upregulated, but only in the EC during the chronic phase. The only glutamate signaling molecule that was acutely upregulated was Vesl/homer, which appears to play a role in synaptic potentiation (Hennou et al, 2003). Increased expression of homer1a, however, has some antiepileptogenic effects as shown in kindled mice with overexpression of homer1a (Potschka et al, 2002).…”

Biology and application of alphaviruses in gene therapy

“…13 Transduction of primary neurons and hippocampal slice cultures has allowed studies on protein transport and localization as well as functional activity, typically by electrophysiological recordings. 14 Moreover, alphavirus vectors have been applied for in vivo administration in the rodent brain. Injection of SIN vectors expressing b-galactosidase into the mouse nucleus caudatus/putamen and nucleus accumbens septi resulted in neuron-specific reporter gene expression.…”