Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior
- 1James H. Clark Center, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA
- 2James H. Clark Center, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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.
Related
- Spatial working memory enhances gamma oscillations in rodent olfactory bulb and medial prefrontal cortex
- From structured knowledge to flexible behaviour: the importance of local prefrontal computations
- Developmental prefrontal myelination shapes inhibitory interneuron function and adult social behavior
- Valine Engages a Prefrontal mGluR5 Allosteric Site to Preserve Social Behavior
- Food Allergy Induces Anxiety-like Behavior and Neuroimmune Dysregulation in the Prefrontal Cortex of Mice
BibTeX
@article{phensy2026prefrontal,
title = {{Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior}},
author = {Aarron J. Phensy and Lara Louise Hagopian and Caitriona M. Costello and Simon Haziza and Omkar Ghenand and Jingcheng Shi and Yanping Zhang and Mark J. Schnitzer and Vikaas Singh Sohal},
journal = {Neuron},
year = {2026},
month = jun,
doi = {10.1016/j.neuron.2026.05.002},
url = {https://doi.org/10.1016/j.neuron.2026.05.002},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior
AU - Aarron J. Phensy
AU - Lara Louise Hagopian
AU - Caitriona M. Costello
AU - Simon Haziza
AU - Omkar Ghenand
AU - Jingcheng Shi
AU - Yanping Zhang
AU - Mark J. Schnitzer
AU - Vikaas Singh Sohal
PY - 2026
DA - 2026/06/08
JO - Neuron
DO - 10.1016/j.neuron.2026.05.002
UR - https://doi.org/10.1016/j.neuron.2026.05.002
AB - 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.
SN - 0896-6273
SN - 1097-4199
ER -