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.
Highlights
GABAergic interneurons play an essential role in maintaining a fine-tuned excitation-inhibition balance in the brain
The molecular classifications of interneurons are divided into five subgroups based on the expression of specific molecular markers: [1] parvalbumin (Pv) in chandelier and basket cells; [2] somatostatin (SOM); [3] neuropeptide Y (NPY); [4] vasoactive intestinal peptide (VIP); and [5] cholecystokinin (CCK)
This study found significant effects of gender on the glutamatergic neurotransmission onto prefrontal Parvalbumin fast-spiking interneurons (Pv-Fast-spiking interneurons (FSI)) of mice undergoing unpredictable chronic mild stress (UCMS) [59]
Summary
GABAergic interneurons play an essential role in maintaining a fine-tuned excitation-inhibition balance in the brain. The density of excitatory synapses were found to be lower and selectively on Pv interneurons in the dlPFC of schizophrenia patients These results corresponded to deficits in GAD67, suggesting a more precise and cell-type-specific mechanism of cortical dysfunction and cognitive deficit that occurs in schizophrenia [49]. As an important and proper functioning of Pv cells is to repolarize fast and relies on calcium sequestration, it is possible that genes responsible for calcium signaling are defective, causing Pv-FSI to malfunction altogether Another interesting aspect of Pv interneurons in the brain is the connections they form with cellular structures. Efforts to understand this mechanism and the behavioral antidepressant effects calls for the consideration
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