Parallel information transmission and circuit refinement of the corticostriatal system

Abstract

The brain is a complex organ that not only gathers copious amounts of information, but also interprets and reacts to information gathered. In the present study we sought to understand how relevant information for a complex experience (cocaine) was transmitted from regions throughout the brain to cocaine-activated striatal cells producing an overall phenotype expected from mice under a strong cocaine experience. To accomplish this, Arc/Ai14 mice were first exposed to repeated prior intra-peritoneal cocaine injections, after which striatal injections of AAV-DIO-TVA adeno-associated virus (AAV) were performed. Post AAV injection, cocaine-activated cells were TRAPed, and finally (EnvA)SAD-ΔG-GFP rabies virus (RV) was injected into the striatum allowing for brain wide monosynaptic retrograde tracing of inputs (cocaine-activated inputs indicated by yellow fluorescence) onto cocaine-activated striatal MSNs. While data is still being tabulated, preliminary data suggests an increase in co-connectivity between cocaine-activated orbitofrontal and medial cortical neurons (retrosplenial/cingulate) and cocaine-activated striatal cells. Thus, preliminary data suggest that chronic cocaine pre-exposure lead to corticostriatal circuit refinement.