PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders

Abstract

Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV) GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC) in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I) in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.

Adolescent cocaine exposure enhances the GABAergic transmission in the prelimbic cortex of adult mice

“…Most pyramidal neurons at layer V of PrL are projecting neurons that send efferent signals to innervate the function of other brain regions, and their function (activity) has been controlled by integrating the E/I inputs on them. The balance of E/I is essential for proper PFC information processing, and disrupting E/I balance induces impairments in a range of PFC-dependent behaviors (29,30). GABAergic interneurons are powerful regulators for the balance of E/I because of their inhibitory transmission in the brain.…”

Inducible and reversible silencing of the Pvalb gene in mice: An in vitro and in vivo study

“…The subpopulation of PV-immunoreactive (PV + ) neurons, hereafter called Pvalb neurons (irrespective of PV expression levels), have become very popular in the last few years due to their emerging role in neuropsychiatric disorders such as schizophrenia and autism spectrum disorder (ASD) (Ferguson & Gao, 2018;Marin, 2012). The study of Pvalb neurons is facilitated by the availability of several transgenic mouse lines; up to date, fluorescent protein expression such as GFP or RFP have been targeted to Pvalb neurons to facilitate their direct identification (Kaiser, Ting, Monteiro, & Feng, 2016;Meyer, Katona, Blatow, Rozov, & Monyer, 2002); in addition, mouse lines expressing the Cre-recombinase (Hippenmeyer et al, 2005) selectively in Pvalb neurons, as well as PV-knockout (PV −/− ) mice (Schwaller et al, 1999) are available from common repositories.…”

Layer‐ and Cell‐Specific Recruitment Dynamics during Epileptic Seizures In Vivo

“…One of the basic features of the cortical network is a delicate balance between excitatory and inhibitory forces, termed E/I balanced network state . The main excitatory forces driving the cortical network are the long‐range and local recurrent excitatory inputs and dendritic amplification mechanisms, whereas the main inhibitory forces in the network are the different subclasses of inhibitory INs .…”

“…[13][14][15] One of the basic features of the normal cortical network is a balanced excitation-inhibition (E/I) state, where feedforward and feedback connections allow inhibitory INs to counterbalance the activity of excitatory neurons. [16][17][18][19] The balanced E/I state of the cortical network allows excitatory PNs to respond and adapt to changing inputs and surroundings, while maintaining normal activity in the network. Seizures probably represent transient imbalance of the E/I ratio, which in turn results in development of a hyperactive and hypersynchronous activity state.…”

“…One of the basic features of the cortical network is a delicate balance between excitatory and inhibitory forces, termed E/I balanced network state. [16][17][18][19] The main excitatory forces driving the cortical network are the long-range and local recurrent excitatory inputs and dendritic amplification mechanisms, whereas the main inhibitory forces in the network are the different subclasses of inhibitory INs. 12,13 Of special interest are the SOM-expressing INs, which selectively innervate the more distal dendrites of PNs, and thus mostly regulate their input and dendritic activity; and the PV-expressing INs, which innervate the perisomatic structures, and thus mostly regulate output activity of PNs.…”