Neural basis of learning and response inhibition in adolescents

NIH RePORTER · NIH · R01 · $520,028 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY/ABSTRACT Understanding how behavioral states are encoded by the adolescent brain may be critical for detection and prevention of brain disorders and reckless behaviors including suicide attempts that emerge in this developmental stage. There is, however, a glaring paucity of data about the neuronal circuity of motivated behavior in adolescent models. This may be primarily due to the technical challenge of executing methods that are routine in adult animals, in adolescent models. We propose to exploit tools and supporting data generated during the last funding period to address the overarching hypothesis that circuit dynamics that support associative learning and ensuing decisions are different in adolescent and adult brains. We have observed that reward (outcome) processing by lateral orbitofrontal cortex (OFC), substantia nigra (SN), and medial dorsal striatum (DS) neurons differ between adolescent and adult rats. In contrast, more traditional “limbic” regions such as the nucleus accumbens (NAc) have nearly identical pattern of reward encoding in adults and adolescents. These are critical observations because appropriate response selection and inhibition toward a desired outcome are dependent on the integrity of OFC-DS circuits. Here we aim to test the specific hypothesis that in adolescents, action-outcome associative learning, and response inhibition and initiation after learning, are computed differently in DS-OFC circuits, but not NAc-OFC circuits. To test this hypothesis, we have developed an action-guided behavior task to assess associative learning and response inhibition which can be (1) implemented during the short rodent adolescent period and (2) combined with multiregional electrophysiology recording and local opto- or chemo-genetic circuit manipulation. We propose three aims. The first two aims assess similarities, or differences, in neuronal processing of the same behavioral events in each circuit in adolescents and adults. A third aim will focus on selective pathway manipulation to characterize potential mechanisms that contribute to the different circuit dynamics observed in adolescents. Regardless of the outcome, completion of this work will provide valuable mechanistic data about the neuronal basis of learning and response inhibition in the adolescent brain.

Key facts

NIH application ID
10844587
Project number
5R01MH048404-31
Recipient
OREGON HEALTH & SCIENCE UNIVERSITY
Principal Investigator
BITA MOGHADDAM
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$520,028
Award type
5
Project period
1992-09-15 → 2027-05-31