Spillover-Mediated Feedforward Inhibition Functionally Segregates Interneuron Activity

Luke T. Coddington, Stephanie Rudolph, Patrick VandeLune, Linda Overstreet-Wadiche, Jacques I. Wadiche

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Neurotransmitter spillover represents a form of neural transmission not restricted to morphologically defined synaptic connections. Communication between climbing fibers (CFs) and molecular layer interneurons (MLIs) in the cerebellum is mediated exclusively by glutamate spillover. Here, we show how CF stimulation functionally segregates MLIs based on their location relative to glutamate release. Excitation of MLIs that reside within the domain of spillover diffusion coordinates inhibition of MLIs outside the diffusion limit. CF excitation of MLIs is dependent on extrasynaptic NMDA receptors that enhance the spatial and temporal spread of CF signaling. Activity mediated by functionally segregated MLIs converges onto neighboring Purkinje cells (PCs) to generate a long-lasting biphasic change in inhibition. These data demonstrate how glutamate release from single CFs modulates excitability of neighboring PCs, thus expanding the influence of CFs on cerebellar cortical activity in a manner not predicted by anatomical connectivity

Original languageEnglish (US)
Pages (from-to)1050-1062
Number of pages13
JournalNeuron
Volume78
Issue number6
DOIs
StatePublished - Jun 19 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Spillover-Mediated Feedforward Inhibition Functionally Segregates Interneuron Activity'. Together they form a unique fingerprint.

Cite this