Transcript T-type calcium channels play a key role in GABAergic

Center for Translational Neuroscience
Distinguished Lecture Series
Rayford Auditorium, Biomed II Bldg., 12 noon
Tuesday, August 17, 2010
“T-type calcium channels play a key role in
GABAergic thalamocortical alterations and
hyperlocomotion mediated by repetitive cocaine
administration ”
Francisco J. Urbano, PhD
Research Scientist, CONICET,
Instituto de Fisiologia, Biologia,
y Neurociencias
University of Buenos Aires
Buenos Aires, Argentina
Abnormalities in both thalamic and cortical areas have been reported in human
cocaine addicts using noninvasive functional magnetic resonance imaging.
Given the substantial involvement of the thalamocortical system in sensory
processing and perception, we used behavior (hyperlocomotor activity) and
electrophysiology-based protocols (EEG and patch-clamp recordings) to attempt
to characterize of cocaine effects on thalamocortical circuits in mice. We studied
mice in vivo and in vitro after cocaine “binge”-like repetitive administration
(i.p., 3x15 mg/kg, 1 hour apart), in comparison to mice injected with saline.
Both systemic and bath-application of the T-type calcium channels blockers
mibefradil and 2-octanol were tested on cocaine-induced thalamocortical
alterations.
Our results indicated that thalamocortical dysfunction observed in cocaine abusers
might be due to two distinct but additive events: 1) increased T-type calcium
channel-dependent, low frequency oscillatory thalamocortical activity, and 2) over
inhibition of VB neurons that can abnormally “lock” the thalamocortical system at
low frequencies.