Jacques WADICHE Local and diffuse actions of glutamate
IBENS Neuroscience Seminar
11h
Le séminaire de Jacques Wadichet (University of Alabama at Birmingham Medical School) aura lieu dans la salle 316, IBENS 46 rue d’Ulm 75005 Paris
Glutamate signaling is often viewed as a highly local process in which transmitter released at anatomically defined synapses activates precisely aligned postsynaptic receptors. However, glutamate can also diffuse beyond the synaptic cleft, influencing nearby cells and receptors in ways that are not captured by classical wiring diagrams. In this talk, I will discuss how both local and diffuse glutamate signaling shape excitatory transmission in the cerebellar cortex. First, I will show that spillover from climbing fibers excites molecular layer interneurons (MLIs) through extrasynaptic mechanisms, functionally segregating interneurons according to their spatial relationship with the release site and altering inhibition of neighboring Purkinje cells. Next, I will describe how climbing fiber spillover can also recruit Ca2+-permeable AMPA receptors at parallel fiber synapses, revealing a form of “spill-in,” in which glutamate released from one pathway engages receptors associated with another. Finally, I will present evidence that the glutamate concentration landscape itself regulates key AMPA receptor properties, demonstrating that receptor behavior is shaped not only by subunit composition but also by the amount of glutamate reaching the receptor. Together, these findings support a broader view of excitatory signaling in which glutamate acts both locally and diffusely to influence receptors, synapses, and circuits.