Optogenetic manipulation of interneuron function. (360G-Wellcome-089924_Z_09_Z)

Our broad goal is to understand how different populations of interneurons contribute to signal processing and oscillations. We will also apply the tools developed here to interrupt experimental seizure activity. Briefly, we will: (1) apply our insights in interneuron lineage to target expression of channelrhodopsin2 (ChR2) to distinct populations of interneurons, focusing initially on those dependent on the transcription factor Lhx6; (2) complement mouse genetics with an existing AAV-based me thod to achieve conditional expression of ChR2 in mice expressing Cre recombinase under the control of Lhx6, parvalbumin and somatostatin; (3) investigate the roles of Lhx6-, parvalbumin- and somatostatin-positive interneurons in oscillatory synchrony in the hippocampus; (4) understand how long-term plasticity of synaptic transmission between principal cells and interneurons affects signal processing; (5) examine the roles of interneurons in the early stages of cortical visual processing; and (6) test the feasibility of a new anti-epileptic strategy that relies on optical activation of interneurons to interrupt seizures