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An Operant Intra-/Extra-dimensional Set-shift Task for Mice

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Published on: January 22, 2016

Interneurons are necessary for coordinated activity during reversal learning in orbitofrontal cortex.

Gregory B Bissonette¹, Geoffrey Schoenbaum², Matthew R Roesch³

¹Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore; Program in Neuroscience, University of Maryland, Baltimore; Department of Psychology, University of Maryland, College Park.

Biological Psychiatry

|September 7, 2014

Summary

Mice with Plaur gene mutations show impaired reversal learning due to dysfunctional parvalbumin interneurons in the orbitofrontal cortex, impacting decision-making and outcome representation in neuropsychiatric disorders.

Keywords:

Autism Interneuron OFC Parvalbumin Plaur Reversal learning Schizophrenia

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Area of Science:

Neuroscience
Cognitive Science
Genetics

Background:

Gamma-aminobutyric acidergic (GABAergic) interneuron dysfunction is linked to cognitive deficits in neuropsychiatric disorders like schizophrenia, autism, and epilepsy.
Mice with Plaur gene mutations, associated with schizophrenia, exhibit deficits in frontal cortical parvalbumin-expressing interneurons and impaired reversal learning.

Purpose of the Study:

To investigate the role of parvalbumin interneurons in the orbitofrontal cortex during reversal learning.
To understand the neural mechanisms underlying cognitive deficits in Plaur mutant mice.

Main Methods:

Recorded single unit activity from control and Plaur mouse neurons during a serial reversal task.
Analyzed neural activity in relation to decision choices, reward receipt, and behavioral performance.

Main Results:

Control neurons showed strong responses correlated with behavioral performance; Plaur mice had diminished neural selectivity for decisions and downscaled reward encoding.
Plaur mice exhibited enhanced baseline firing but reduced encoding of expected outcomes during decision-making.
A significant reduction in neurons encoding expected outcomes was observed in Plaur mice.

Conclusions:

Parvalbumin interneurons are crucial for representing outcomes in the orbitofrontal cortex.
Deficits in GABAergic inhibition impair selective neural firing, leading to behavioral inflexibility.
These findings offer a potential explanation for cognitive control disorders associated with GABAergic interneuron loss in neuropsychiatric conditions.