Ventral Tegmental Area (VTA) dopaminergic neurons encode reward prediction errors and signal the incentive salience of sensory cues (1-3). Burst firing of these neurons result in phasic dopamine release in cortical and limbic terminal fields such as the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), which acts to modulate postsynaptic neuronal firing (7) to promote changes in motivated behavioral output (8-10). However, it remains unclear how VTA dopaminergic activity affects large-scale brain network functional connectivity, and how these brain network dynamics are altered following repeated cocaine self-administration. To address this, we will utilize a highly innovative approach that couples optogenetic stimulation techniques with functional magnetic resonance imaging (fMRI) technology in an in vivo rat model to determine whether selective stimulation of VTA dopaminergic neurons alters functional connectivity between multiple, anatomically distinct brain regions. The experiments proposed in this application would further our understanding on how aberrant dopaminergic signaling may degrade optimal neuronal network dynamics, which in turn may shift brain activity to promote maladaptive states.
Addiction is a chronically, relapsing disease characterized by compulsive drug-seeking and drug-taking behavior despite adverse health, personal and societal consequences. Addiction may arise in part from dysregulated activity of VTA dopaminergic neurons, as well as from more global maladaptation in neurocircuit function. The research generated in this proposal will investigate how the selective activation of DA neurons within the midbrain alters global patterns of brain connectivity, and how these brain network dynamics are altered following drug exposure.
|Decot, Heather K; Namboodiri, Vijay M K; Gao, Wei et al. (2017) Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons. Neuropsychopharmacology 42:615-627|