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Functional Role of the Thalamus in Coordinating Dorsolateral Striatum Encoding of Habit Learning

Award Number: F31DA065469
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Functional Role of the Thalamus in Coordinating Dorsolateral Striatum Encoding of Habit Learning - PROJECT SUMMARY Behavioral control is dynamically regulated by the interplay between flexible, goal-directed actions and efficient, automatic habits. Goal-directed behavior, driven by knowledge of the action-outcome (A-O) relationship, allows for behavioral flexibility, while habits are automatic responses that persist despite changes in outcome value. The disruption of this balance, where the habit system dominates flexible control, constitutes the core pathology underlying persistent, compulsive behaviors seen across many neuropsychiatric disorders, including substance use disorder (SUD). Defining the neural mechanisms that support the emergence of habitual behavior is essential for identifying how and when this process becomes maladaptive. Although extensive preclinical research has established the dorsolateral striatum (DLS) as required for the expression of habitual behavior, the upstream, circuit-level mechanisms that modulate this behavioral transition remain poorly understood. Specifically, how upstream inputs alter population-level computations—such as ensemble structure and network dynamics—to drive the shift from goal-directed to habitual behavior remains a critical knowledge gap. One promising candidate for regulating this process is the paraventricular thalamus (PVT), a region known for its role in top-down control of motivated behavior. Previous findings from our lab have shown that PVT projections can inhibit goal-directed behavior by engaging inhibitory interneurons in the nucleus accumbens (NAc), which in turn regulate the activity of striatal output neurons. My preliminary data extends this work to the DLS, demonstrating that the PVT also robustly innervates inhibitory interneurons in this region. Functionally, optogenetic activation of PVT terminals in the DLS resulted in a significant attenuation of habitual responding, suggesting that PVT- DLS signaling influences the emergence of habitual behavior by modulating DLS circuit activity. My overarching hypothesis is that PVT projections to the DLS regulate the transition between goal-directed and habitual behavior through feedforward inhibition of DLS output neurons. To test this hypothesis, in Aim 1 I will use optogenetics to determine the functional necessity of PVT-DLS output circuitry for goal-directed and habit-like behaviors. Next, in Aim 2 I will use in vivo calcium imaging in a validated head-fixed paradigm to track DLS neuronal activity as mice transition from goal-directed to habitual behavior, determining how PVT input influences ensemble recruitment and population-level firing patterns. Ultimately, this research aims to provide crucial insight into how thalamostriatal signaling regulates the balance between goal-directed and habitual control. By defining the circuit mechanisms that drive behavioral inflexibility, this work will offer new avenues for intervention in SUD and other neuropsychiatric disorders characterized by compulsive, habitual behavior (e.g., OCD, Tourette’s Syndrome).


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	1	7/16/2026	NEW	$0
2026	2026	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	1	7/16/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Functional Role of the Thalamus in Coordinating Dorsolateral Striatum Encoding of Habit Learning

Award Number: F31DA065469

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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