Coordination of brain network dynamics by dopaminergic activity

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

? DESCRIPTION (provided by applicant): 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.