UC San Diego

The complex tangle of synaptic connections made by the myriad of neural cell types in mammalian nervous system, each with their own genetic, chemical, and electrophysiological properties, are the basis of neural computation and thus perception, motivation, and behavior. As such, it is a fundamental task of neuroscience to map neural connectivity in a cell-type specific manner and develop robust technologies to this end. This dissertation describes two such technologies. First, targeted deletion and in vivo transcomplementation of the Herpes Simplex Virus 1 (HSV) gene UL6 in the anterograde strain H129 allows for the selective labeling of postsynaptic populations from specific neuronal cell types in a cre-dependent manner. Second, the cause of transgene expressing in off-target cells from recombinase-dependent recombinant adeno-associated virus (AAV) will be described, along with efforts toward improved methods in AAV production for “leakless” expression of sensitive transgenes. Both techniques will expand the available toolkit of the modern systems neuroscientist and provide a means by which to tackle previously intractable questions.