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This Article Full Text Full Text (PDF) All Versions of this Article: 102/2/682    most recent 00134.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Carrillo-Reid, L. Articles by Bargas, J. PubMed PubMed Citation Articles by Carrillo-Reid, L. Articles by Bargas, J.

Muscarinic Enhancement of Persistent Sodium Current Synchronizes Striatal Medium Spiny Neurons

Departamento de Biofísica, Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Federal District, Mexico

Submitted 13 February 2009; accepted in final form 21 May 2009

Network dynamics denoted by synchronous firing of neuronal pools rely on synaptic interactions and intrinsic properties. In striatal medium spiny neurons, N-methyl-D-aspartate (NMDA) receptor activation endows neurons with nonlinear capabilities by inducing a negative-slope conductance region (NSCR) in the current–voltage relationship. Nonlinearities underlie associative learning, procedural memory, and the sequential organization of behavior in basal ganglia nuclei. The cholinergic system modulates the function of medium spiny projection neurons through the activation of muscarinic receptors, increasing the NMDA-induced NSCR. This enhancement is reflected as a change in the NMDA-induced network dynamics, making it more synchronous. Nevertheless, little is known about the contribution of intrinsic properties that promote this activity. To investigate the mechanisms underlying the cholinergic modulation of bistable behavior in the striatum, we used whole cell and calcium-imaging techniques. A persistent sodium current modulated by muscarinic receptor activation participated in the enhancement of the NSCR and the increased network synchrony. These experiments provide evidence that persistent sodium current generates bistable behavior in striatal neurons and contributes to the regulation of synchronous network activity. The neuromodulation of bistable properties could represent a cellular and network mechanism for cholinergic actions in the striatum.