# A novel thalamic circuit for behavioral reinforcement

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $21,356

## Abstract

Project Summary
Striatal dopamine release is critical for behavioral reinforcement. Manipulations in dopaminergic signaling by
drugs of abuse produce aberrant behavioral reinforcement. Elucidating the neural circuits that regulate striatal
dopamine release is critical to both understanding the mechanisms of drugs of abuse and developing novel
treatments for addiction. I have preliminarily discovered a novel circuit that elicits dopamine release in the dorsal
striatum: optogenetic activation of a glutamatergic projection arising from a rostral collection of intralaminar nuclei
in the thalamus (rILN) drives striatal cholinergic interneurons (ChIs) that, in turn, axo-axonically synapse on
nigrostriatal terminals to powerfully induce dopamine release in the dorsal medial striatum. In vivo activation of
this pathway produces behavioral reinforcement in mice. Such direct thalamic control of local striatal dopamine
release represents a paradigm shift in our understanding of the contributions of axo-axonic synapses to
behavioral reinforcement. Based on my preliminary findings, I hypothesize that the rILN drives ChI-dependent
striatal dopamine release for behavioral reinforcement. I will investigate this hypothesis in two aims using in vivo
and ex vivo strategies: 1) I will use in vivo optogenetics, pharmacology, and viral-transgenic approaches to test
my prediction that rILN-induced behavioral reinforcement is dependent on ChI activity and dopamine signaling;
and 2) I will test my prediction that rILN-evoked dopamine release requires ChI-mediated activation of nicotinic
acetylcholine receptors using ex vivo optogenetics and fast scan cyclic-voltammetry. I will also employ whole-
cell patch clamp electrophysiology to test my prediction that rILN signaling preferentially excites D1 receptor-
expressing medium spiny neurons, activation of which is linked to behavioral reinforcement. The results of this
study will significantly advance our knowledge of a novel non-canonical dopamine release circuit and provide
the PI with substantial training opportunities in neurophysiology.

## Key facts

- **NIH application ID:** 9971510
- **Project number:** 5F31DA047014-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Kara Cover
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,356
- **Award type:** 5
- **Project period:** 2018-07-23 → 2020-12-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971510

## Citation

> US National Institutes of Health, RePORTER application 9971510, A novel thalamic circuit for behavioral reinforcement (5F31DA047014-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971510. Licensed CC0.

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