Mutations in the CaV2.1alpha1 gene cause familial hemiplegic migraine type 1 (FHM1), a rare subtype of migraine with aura. FHM1 mutations produce gain-of-function of neuronal CaV2.1 channels as well as facilitation of cortical spreading depression in knockin (KI) mice in vivo. We recorded from synaptically connected pairs of pyramidal cells and fast-spiking interneurons in layer 2/3 of acute thalamocortical slices from KI mice carrying the R192Q FHM1 mutation, to investigate the consequences of this mutation on synaptic transmission. We found that in KI mice interneurons, the average amplitude of the excitatory postsynaptic potential (EPSP) evoked by suprathreshold stimulation of the presynaptic pyramidal cell, was significantly larger than in the WT. This increase was accompanied by a decrease in the failure rate and a decrease in the coefficient of variation (CV). The short term depression was stronger in KI mice, supporting the conclusion that the mutation leads to an increased probability of release at this synapse. Conversely, the inhibitory postsynaptic potentials (IPSPs) recorded from the pyramidal cell, due to AP firing of the interneuron, had the same amplitude, failure rate and CV for both WT and KI mice, indicating no effect of the mutation on this synapse. We are now investigating a possible differential effect induced by the mutation on the properties of AP firing of pyramidal cells and fast-spiking interneurons, which could also contribute to these results.