The Role of Parvalbumin Interneurons in Neurotransmitter Balance and Neurological Disease

Abstract

While great progress has been made in the understanding of neurological illnesses, the pathologies, and etiologies that give rise to these diseases still remain an enigma, thus, also making treatments for them more challenging. For effective and individualized treatment, it is beneficial to identify the underlying mechanisms that govern the associated cognitive and behavioral processes that go awry in neurological disorders. Parvalbumin fast-spiking interneurons (Pv-FSI) are GABAergic cells that are only a small fraction of the brain's neuronal network, but manifest unique cellular and molecular properties that drastically influence the downstream effects on signaling and ultimately change cognitive behaviors. Proper brain functioning relies heavily on neuronal communication which Pv-FSI regulates, excitatory-inhibitory balances and GABAergic disinhibition between circuitries. This review highlights the depth of Pv-FSI involvement in the cortex, hippocampus, and striatum, as it pertains to expression, neurotransmission, role in neurological disorders, and dysfunction, as well as cognitive behavior and reward-seeking. Recent research has indicated that Pv-FSI play pivotal roles in the molecular pathophysiology and cognitive-behavioral deficits that are core features of many psychiatric disorders, such as schizophrenia, autism spectrum disorders, Alzheimer's disease, and drug addiction. This suggests that Pv-FSI could be viable targets for treatment of these disorders and thus calls for further examination of the undeniable impact Pv-FSI have on the brain and cognitive behavior.

Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood

“…GABAergic PV interneurons constitute around 30%–50% of the total number of inhibitory cells in the neocortex and participate in the control and regulation of cortical networks through local regulation and stabilization of excitatory activity (Batista‐Brito et al, 2020). Thus, PV interneurons contribute to overall excitatory/inhibitory balance (Nahar et al, 2021) which impacts learning and memory behaviors (Murray et al, 2015). Moreover, these neurons regulate neural synchrony within microcircuits (Ruden et al, 2021) and, thus, potentially contribute to functional connectivity deficits observed using resting‐state MRI following AIE exposure (Broadwater et al, 2018; Gómez‐A et al, 2021).…”

Neonatal Oxidative Stress Impairs Cortical Synapse Formation and GABA Homeostasis in Parvalbumin-Expressing Interneurons

“…In some cortical areas, PVALB+ interneurons make up to 50% of the interneuronal population and target up to 200 pyramidal cells per single cell. Even small changes in interneuronal numbers or functionality can interfere with the proper orchestra of neuronal function in distinct cortical areas [ 25 , 58 , 59 ]. Impairments of GABAergic interneurons have been related to preterm birth brain injury and oxidative stress (OS).…”

Functional autapses form in striatal parvalbumin interneurons but not medium spiny neurons

“…PV-positive cells can be found in different brain regions, contributing significantly to information processing in a variety of brain circuits [36]. In the neocortex and hippocampus, PV neurons have been confirmed to have functional autapses; similar to certain types of conventional synapses, these autapses possess two modes of neurotransmitter release, synchronous and asynchronous mode [17,19,37]. Recordings from acute cortical slices revealed that the percentage of autaptic PV cells in rodent (~85%) is more than that found in human (64.3%) [17,19].…”