International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 56 - IMPAIRED THALAMIC SENSORY GATING AND AFFECTIVE DISORDER IN T-TYPE CA2+ CHANNEL MUTANTS

Shin H-S, Choi S, Lee J, Lee S, Kim C, Kim D

Korea Institute of Science & Technology, Seoul, Korea, South

Low threshold Ca2+ currents mediated by α1G T-type channels are responsible for burst spike activities of relay neurons in the thalamus, and have been implicated in diverse physiological and pathological processes. We have previously reported that the knock-out mice for the α1G T-type channels show an enhanced nociceptive response to visceral pain, accompanied by an increase in pain-encoding tonic spikes in the absence of burst firing in thalamic relay neurons (Science, 2003). These results suggested that α1G T-type channels are involved in the thalamic sensory gating function, blocking the relay of the pain signals to the cortex. We have further examined this point by using several different sensory modalities: startle responses to auditory or tactile stimuli, and responses to chronic inflammatory pain. First, the mutant mice showed an enhanced startle response to auditory stimulations. The enhanced response appeared to be due to a change in the thalamic function instead of a peripheral problem, because auditory brainstem recordings (ABR), which measures primary neural signals induced by auditory stimuli, revealed no difference in the response pattern between the two genotypes. Second, the mutant also displayed an enhanced startle response to tactile stimuli compared to wildtype. Third, the mutant showed a selective increase in the late phase pain response to an intradermal injection of formalin into the hindpaw, a response under the control of a supraspinal mechanism. In summary, therefore, the mutant showed enhanced responses to sensory inputs of four different modalities. These results strongly support the idea that α1G T-type channels play an important role in the sensory gating in the thalamus. We suggest that the burst spikes induced by the low threshold Ca2+ currents are the key element in this thalamic function. Behavioral studies revealed that the mutant mice showed a mania-like affective disorder, increased alcohol preference, and a resistance to alcohol-induced hypnotic effect. These behavioral consequences will be discussed with regard to the sensory gating failure of the mutant.

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