Presentation Title

Projections from the paraventricular nucleus of the thalamus to the striatum can evoke dopamine transients

Faculty Mentor

Michael Authement, Veronica Alvarez

Start Date

23-11-2019 8:00 AM

End Date

23-11-2019 8:45 AM

Location

55

Session

poster 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

The paraventricular nucleus of the thalamus (PVT) is a brain region important for behavioral adaptations to stress that was recently shown to mediate aversive symptoms of morphine withdrawal. Here we focused on a pathway from the PVT to striatum, a part of the basal ganglia involved in motor learning, motivation, and reward processing. While this pathway is important in mediating opiate withdrawal symptoms, as well as encoding other aversive states, characterization of this circuit is incomplete. We hypothesize that like other thalamic as well as cortical inputs to the striatum, PVT inputs trigger striatal dopamine release by stimulating striatal cholinergic interneurons which in turn release acetylcholine that binds to presynaptic nicotinic acetylcholine receptors on dopamine axons to release dopamine. We also hypothesize that this circuitry is sensitive to the acute application drugs of abuse such as morphine. We tested this hypothesis using a combination of pharmacology, fast-scan cyclic voltammetry (FSCV) and optogenetics in ex vivo mouse brain slices containing the striatum. Channelrhopdopsin-2 (ChR2), a light activated ion channel was specifically expressed in the PVT, allowing for activation of PVT inputs to the striatum while measuring dopamine with FSCV. A single pulse of 470nm light was sufficient to evoke PVT-triggered dopamine transients in the striatum. Application of DHBE, a nicotinic acetylcholine receptor antagonist to brain slices fully blocked PVT-triggered dopamine transients. NBQX and CPP, AMPA receptor and NMDA receptor blockers, respectively, also blocked dopamine transients, further supporting our hypothesis. Furthermore, PVT-triggered DA transients were inhibited by acute application of cocaine and morphine, suggesting this mechanism of dopamine signaling in the striatum is sensitive to drugs of abuse. These findings contribute to our understanding of how the PVT influences striatal dopamine release at a circuitry level and how it is modulated by drugs of abuse.

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Nov 23rd, 8:00 AM Nov 23rd, 8:45 AM

Projections from the paraventricular nucleus of the thalamus to the striatum can evoke dopamine transients

55

The paraventricular nucleus of the thalamus (PVT) is a brain region important for behavioral adaptations to stress that was recently shown to mediate aversive symptoms of morphine withdrawal. Here we focused on a pathway from the PVT to striatum, a part of the basal ganglia involved in motor learning, motivation, and reward processing. While this pathway is important in mediating opiate withdrawal symptoms, as well as encoding other aversive states, characterization of this circuit is incomplete. We hypothesize that like other thalamic as well as cortical inputs to the striatum, PVT inputs trigger striatal dopamine release by stimulating striatal cholinergic interneurons which in turn release acetylcholine that binds to presynaptic nicotinic acetylcholine receptors on dopamine axons to release dopamine. We also hypothesize that this circuitry is sensitive to the acute application drugs of abuse such as morphine. We tested this hypothesis using a combination of pharmacology, fast-scan cyclic voltammetry (FSCV) and optogenetics in ex vivo mouse brain slices containing the striatum. Channelrhopdopsin-2 (ChR2), a light activated ion channel was specifically expressed in the PVT, allowing for activation of PVT inputs to the striatum while measuring dopamine with FSCV. A single pulse of 470nm light was sufficient to evoke PVT-triggered dopamine transients in the striatum. Application of DHBE, a nicotinic acetylcholine receptor antagonist to brain slices fully blocked PVT-triggered dopamine transients. NBQX and CPP, AMPA receptor and NMDA receptor blockers, respectively, also blocked dopamine transients, further supporting our hypothesis. Furthermore, PVT-triggered DA transients were inhibited by acute application of cocaine and morphine, suggesting this mechanism of dopamine signaling in the striatum is sensitive to drugs of abuse. These findings contribute to our understanding of how the PVT influences striatal dopamine release at a circuitry level and how it is modulated by drugs of abuse.