# Interactions between orbitofrontal cortex and mediodorsal thalamus in cue- and value-based decision making

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $235,500

## Abstract

Abstract
Our health and well being depend on our ability to make adaptive decisions that take into account information
about the expected value and availability of potential behavioral goals. It is believed that dysfunction within the
neural systems that support goal-directed decision making can result in maladaptive reward-seeking behavior
that is either exaggerated and difficult to control, such as with compulsive drug seeking and overeating, or
becomes weakened to an unhealthy degree, such as with the apathy apparent in various psychiatric and
neurodegenerative disorders (e.g., Alzheimer's disease and schizophrenia). Advances in our understanding of
the neural systems that support adaptive decision making are needed so that we are better able to pinpoint the
specific aberrations in neural function that give rise to pathological forms of reward seeking. The current project
will use an integrative approach to provide novel tests of the decision-making functions of anatomically distinct
pathways connecting the medial (MOFC) and lateral (LOFC) orbitofrontal cortices to each other and to the
mediodorsal thalamus (MDTHAL). Our behavioral approach will make use of well-validated assays of cue- and
value-based decision making in rats. The influence of reward-predictive cues on action selection will be probed
using the outcome-specific Pavlovian-to-instrumental transfer task, in which noncontingent presentations of a
cue that signals the availability of a specific reward outcome (e.g., sucrose solution) biases rats to selectively
pursue that outcome instead of a different but equally valuable outcome (e.g., grain pellets). To probe value-
based decision making, we will use outcome-specific reward devaluation tasks, in which rats demonstrate their
capacity to flexibly suppress their performance of instrumental actions or Pavlovian conditioned approach
responses when an expected reward is devalued through specific satiety. In Aim 1 we will virally express
hM4Di, a Gi-coupled DREADD (Designer Receptors Exclusively Activated by Designer Drugs), in the MOFC,
LOFC, or MDTHAL, allowing us to determine how inhibiting neurons in these areas (via systemic hM4Di
activation) or specific pathways connecting these areas (via local hM4Di activation) impacts cue-based
decision making (Pavlovian-instrumental transfer). In Aim 2 we will use the same basic chemogenetic
approach to investigate the neural circuitry required for value-based decision making (instrumental and
Pavlovian reward devaluation). Together these experiments will provide rigorous tests of innovative
hypotheses regarding the behavioral functions of these understudied pathways within the broader
orbitothalamic network. Given evidence that dysfunction within these pathways contributes to aberrations in
reward-motivated behavior, we believe that this work will have a broad scientific impact, and will lay the
groundwork for our own future research investigating neural mechanisms of maladaptive decisions.

## Key facts

- **NIH application ID:** 9979350
- **Project number:** 1R21DA046667-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Sean Bjorn Ostlund
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,500
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979350

## Citation

> US National Institutes of Health, RePORTER application 9979350, Interactions between orbitofrontal cortex and mediodorsal thalamus in cue- and value-based decision making (1R21DA046667-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979350. Licensed CC0.

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