Connectivity and function of inhibitory neurons in the primate visual cortex

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SUMMARY The goals and specific aims of the present Administrative Supplement application are unchanged with respect to the parent R01 award. Here we request additional funds for unanticipated expenses within the original scope of the project. In the original application we proposed to use viral vectors that specifically infect somatostatin (SOM) and parvalbumin (PV) inhibitory neurons in non-human primate cortex. These viral vectors were generated and provided by our collaborators Dr Zemelman at UT Austin (a subcontract PI in the first two years of the project), Dr Dimidschstein (Broad Institute), and Dr Horwitz (Univ. of Washington). In the first two years of the project, we tested and validated the 3 types of PV-specific viruses generated by our collaborators. Dr Dimidschstein’s virus showed the highest specificity for PV neurons. Unfortunately, however, Dr Dimidschstein has recently left academia and is no longer in a position to provide us with this vector and its variants at no cost. We have, therefore, started a collaboration with Drs Gordon Fishell (Harvard) and Dr. Gabrielle Pouchelon (Cold Spring Harbor) to generate variants of the Dimidschstein PV-specific virus that express the necessary genes to perform the TRIO experiments proposed in Aim 1 of the project, to trace anatomical inputs to PV cells. Moreover, we are working with private companies (Genewiz and Addgene) and the U Penn Viral Vector Core to generate variants of this PV-specific virus carrying the genes for excitatory and inhibitory opsins; these are necessary to address Aim 3 of the project. These new approaches require significant additional expenses which we cannot cover with the funds awarded. The requested cost increases would allow us to address part of Aim1 and Aim3 of the project using vectors with >90% specificity as validated by our studies performed in the initial years of the project. We will make accessible to the community the vectors generated with the additional funds.