Work

Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior

Year: 2026

Type: article

Abstract: Cognitive dysfunction in conditions such as schizophrenia involves disrupted communication between the prefrontal cortex (PFC) and the mediodorsal thalamus (MD). Parvalbumin interneurons (PVIs) are known to regulate PFC microcircuits and generate synchronized gamma-frequency (∼40 Hz) neural oscillations that are recruited during many executive functions, necessary for cognitive flexibility, and deficient in schizophrenia. While targeting PVI-mediated gamma oscillations holds great therapeutic promise, their nature and specific functions, e.g., for regulating PFC→MD communication, remain elusive. Using dual-color voltage indicators and optogenetics in mice, we reveal that PVIs dynamically synchronize with MD-projecting PFC neurons both locally and contralaterally, creating multiple distinct circuit-specific patterns of distributed gamma synchronization that are recruited in a behaviorally specific manner to support particular aspects of flexible behavior. Thus, gamma oscillations are not unitary phenomena characterized by one microcircuit-wide pattern of synchrony. Rather, they comprise diverse motifs, defined by specific cell types and phase relationships, that are dynamically recruited for specific functions.

Source: Neuron

DOI: 10.1016/j.neuron.2026.05.002

Authors: Aarron Justin Phensy, Lara Louise Hagopian, Caitriona Min-Yi Costello, Simon Haziza, Omkar Ghenand, Jingcheng Shi, Yanping Zhang, Mark J. Schnitzer, Vikaas Singh Sohal

Institutions: University of California, San Francisco, Stanford University, Howard Hughes Medical Institute

Language: English

Topic: Neural dynamics and brain function

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $10,400

Funders: Brain and Behavior Research Foundation, National Institutes of Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke

Awards: How is anxiety-related information relayed across hippocampal-prefrontal circuits, G2933388689, How is anxiety-related information relayed across hippocampal-prefrontal circuits, Restoring cognition by optogenetically rescuing gamma rhythms in PFC interneurons, Using new methods for voltage imaging to assay the engagement of specific cell-types and brain rhythms in prefrontal-dependent cognition., How do parvalbumin interneuron-generated gamma oscillations organize prefrontal networks to promote behavioral adaptation?, Multi-color optical voltage imaging of neural activity in behaving animals, Dissecting neocortical field potential dynamics using optical voltage imaging in genetically targeted cell-types, Neurodevelopmental defects of the thalamocortical pathway as a convergent feature of psychiatric disorders, Improving cognition by understanding and harnessing the plasticity of gamma-generating circuits in prefrontal cortex, Predoctoral Training in Neurobiology

OpenAlex ID: W7163887110

FWCI: 7.531

Cites: 48

Cited by: 5

Related to: 10