Reinforcing Effect of Optogenetic Stimulation of Dorsal Subiculum

Cadle, Brian

Graduate Thesis Or Dissertation

Reinforcing Effect of Optogenetic Stimulation of Dorsal Subiculum Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/zk51vg91f

Abstract

The subiculum is a subregion of the hippocampus that sends projections from the hippocampus to several cortical and limbic structures involved in mediating motivated behaviors such as the medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), amygdala, and hypothalamus. Electrophysiological and pharmacological studies have demonstrated that the subiculum itself can modulate certain motivated behaviors. Prior work has often focused on the ventral portion of the subiculum (vSUB), as electrically stimulating the vSUB can induce reinstatement of cocaine seeking behavior. However, no studies to date have shown whether stimulation of the dorsal subiculum (dSUB) can affect operant responding or motivated behavior. Here we demonstrate that mice placed in custom built operant nose poke chambers will nose poke for optogenetic stimulation of the dSUB. This reinforcing effect was significantly greater than baseline nose poking rates or poking for a light cue and was dependent on the frequency of stimulation, with increased frequency correlating with increased self-stimulation rates. Stimulating subicular projections to the Nacc also significantly increased self-stimulation rates, indicating a role for dSUB to Nacc projections in mediating the reinforcing effects of self-stimulation. Acute and chronic administration of cocaine had no effect on laser self-stimulation rates, however, administration of dopamine D₁ receptor antagonist SCH-23390 or muscarinic acetylcholine receptor (mAChR) antagonist scopolamine significantly reduced laser self-stimulation, suggesting the involvement of dopaminergic and cholinergic systems in mediating laser self-stimulation's reinforcing effects. Together, this data supports a novel role for dSUB projections to the Nacc in mediating control of operant and motivated behaviors.

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