Cocaine acute “binge” administration results in altered intrinsic properties of thalamocortical neurons in mice

F. J. URBANO; V. BISAGNO; O. D. UCHITEL; R. R. LLINAS

Chicago

Congreso; Society for Neuroscience, 2009.; 2009

Abnormalities in both thalamic and cortical areas have been reported in human cocaine addicts using non-invasive functional MRI. Abnormal thalamocortical rhythms play an important role in the pathophysiology of different neurological and neuropsychiatric diseases, including Parkinson’s disease, schizophrenia, etc., named thalamocortical dysrhythmia syndrome.Since thalamocortical activity is the product of the intrinsic properties of thalamic neurons, their recurrent connectivity with the cortex and the synaptic input from sensory and mesencephalic neurons, we studied thalamocortical function both in vivo and in vitro in mice one hour following i.p. saline or cocaine “binge” administration (3x15mg/Kg, one hour apart), as well as 24 hours after last cocaine injection.Compared to saline, in vivo EEG recordings following cocaine “binge” administration showed a significant increment in low frequencies (reversible after 24 hours), while observing no changes in high frequency gamma activity. In vitro voltage- and current-clamp patch recordings from VB neurons after cocaine “binge” administration showed low threshold spikes (LTS) activation at more negative membrane potentials; and increments in both Ih and low voltage activated T-type calcium currents (CaV3 mediated). Also, a 10 mV negative shift on threshold activation level of T-type current was observed.In conclusion, our results showed an atypically higher activation of T-type calcium currents present on VB relay neurons from cocaine “binge” treated mice, that would increase low frequency oscillatory thalamocortical activity. Thus, suggesting that cocaine acute “binge” induced a transitory thalamocortical dysrhythmia-like state.