Dopaminergic neurotransmission at the D1 family of dopamine receptors (D1 R) is critical for normal cognitive functioning, and impairments in this system are linked with schizophrenic symptomology and cocaine abuse. However, the exact mechanism by which D1R signaling affects these functions is not clear. Studies on individual neurons show that there are specific and complex circuit effects of D1R drugs in the PFC, suggesting a structural component for the actions of dopamine at the D1 and D5 receptors. Thus, the goal of this proposal is to utilize immunohistochemical electron microscopy and co-immunoprecipitation to examine how dopamine acting at D1 and D5 receptors can modulate activity in the PFC.
The first aim will determine the localization of D1 and D5 receptors within specific components of PFC circuitry. Because the effects of D1R activation rely on a complex signal transduction pathway, the second aim will determine if key proteins in this pathway are available to each D1R in specific components of PFC circuitry.
The third aim will extend the neuroanatomical findings by identifying D1R downstream targets such as NMDA, AMPA and GABA receptors that specifically interact with D1 and D5 and two critical D1R signal transduction proteins.
