The tottering (tg) mice have a mutation in the CaV2.1 (P/Q-type) voltage-dependent Ca2+ channel alpha12.1 subunit gene. tg mice show absence epilepsy, which begins at about 3 weeks of age and persists throughout life. Although imbalance between excitatory and inhibitory activity in the thalamocortical network is thought to contribute to the pathogenesis of absence epilepsy, the effect of the mutation on thalamocortical synaptic responses remains unknown. In this study, we showed imbalanced impairment of inhibitory synaptic responses in tg mice, using brain slice preparations. Somatosensory thalamocortical projection makes not only monosynaptic glutamatergic connections but also disynaptic GABAergic connections, which mediate feedforward inhibition, onto layer IV neurons. In tg mice, IPSC amplitudes recorded from layer IV pyramidal cells of the somatosensory cortex in response to thalamic stimulation became disproportionately reduced, compared with EPSC amplitudes, in later developmental stages (P21-30). However, IPSC reduction was not seen in layer IV pyramidal neurons of younger tg mice before the onset of epilepsy (P14-16). These results showed that the feedforward inhibition from the thalamus to layer IV neurons of the somatosensory cortex was severely impaired in tg mice, and that the impairment of the inhibitory synaptic transmission was correlated to the onset of absence epilepsy.
Sasaki S, Huda K, Inoue T, Miyata M & Imoto K (2006) Impaired feedforward inhibition of the thalamocortical projection in epileptic Ca2+-channel mutant mice, tottering. J Neurosci 26:3056-3065.
