Muscarinic Enhancement of Persistent Sodium Current Synchronizes Striatal Medium Spiny Neurons.

LUIS CARRILLO-REID; FATUEL TECUAPETLA; NICOLAS VAUTRELLE; ADÁN HERNÁNDEZ; RAMIRO VERGARA; ELVIRA GALARRAGA; JOSÉ BARGAS

JOURNAL OF NEUROPHYSIOLOGY

American Physiological Society

Lugar: Bethesda ; Año: 2009 vol. 102 p. 682 - 690

0022-3077

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 ssociative 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 enhancementis 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 calciumimaging 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.