Long-range inhibition synchronizes and updates prefrontal task activity

Abstract

Changes in patterns of activity within the medial prefrontal cortex enable rodents, non-human primates and humans to update their behaviour to adapt to changes in the environment—for example, during cognitive tasks1–5. Parvalbumin-expressing inhibitory neurons in the medial prefrontal cortex are important for learning new strategies during a rule-shift task6–8, but the circuit interactions that switch prefrontal network dynamics from maintaining to updating task-related patterns of activity remain unknown. Here we describe a mechanism that links parvalbumin-expressing neurons, a new callosal inhibitory connection, and changes in task representations. Whereas nonspecifically inhibiting all callosal projections does not prevent mice from learning rule shifts or disrupt the evolution of activity patterns, selectively inhibiting only callosal projections of parvalbumin-expressing neurons impairs rule-shift learning, desynchronizes the gamma-frequency activity that is necessary for learning8 and suppresses the reorganization of prefrontal activity patterns that normally accompanies rule-shift learning. This dissociation reveals how callosal parvalbumin-expressing projections switch the operating mode of prefrontal circuits from maintenance to updating by transmitting gamma synchrony and gating the ability of other callosal inputs to maintain previously established neural representations. Thus, callosal projections originating from parvalbumin-expressing neurons represent a key circuit locus for understanding and correcting the deficits in behavioural flexibility and gamma synchrony that have been implicated in schizophrenia and related conditions9,10.

Adolescent Thalamocortical Inhibition Alters Prefrontal Excitation-Inhibition Balance

“…Therefore, the overall increase in inhibition could be due to complex disinhibition between VIP+, SOM+, PV+ and pyramidal cell types. It is unclear why it should be specific only to callosal, intracortical connectivity but some interneurons target callosal projecting pyramidal cells (Pi et al, 2013;Cho et al, 2023).…”

Distinct electrophysiological properties of long‐range GABAergic and glutamatergic neurons from the lateral amygdala to the auditory cortex of the mouse

“…Recent research suggests that approximately 1-10% of cortical GABAergic neurons in rodents, cats and monkeys are categorized as long-range cortical projections (Higo, 2009;Higo et al, 2007;McDonald & Burkhalter, 1993;Tomioka & Rockland, 2007;Tomioka et al, 2005Tomioka et al, , 2015. A growing body of evidence from our laboratory and others indicates that many of these projections arise from somatostatin-expressing neurons (Bertero et al, 2019;Higo, 2009;Higo et al, 2007;Jinno & Kosaka, 2004;McDonald et al, 2012;Melzer & Monyer, 2020;Tomioka & Rockland, 2007;Tomioka et al, 2005), parvalbumin-expressing neurons (Cho et al, 2023;Lee et al, 2017;Melzer et al, 2017) and more recently, vasoactive intestinal peptide-expressing neurons in the hippocampus formation (Francavilla et al, 2018) and in the neocortex (Bertero et al, 2021; for review see: Apicella & Marchionni, 2022). It is worth noting that long-range GABAergic neurons are important circuit elements in many brain areas, such as the spiny projection neurons in the striatum, the Purkinje neurons in the cerebellum, and somatostatin-immunoreactive neurons in the amygdala which project to the entorhinal cortex (McDonald & Zaric, 2015) and to the basal forebrain (McDonald et al, 2012).…”