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

Frontiers in Neural Circuits, Journal Year: 2018, Volume and Issue: 12

Published: May 16, 2018

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 contribution of certain neuronal subpopulations refining representations. However, growing evidence supports a fundamental fast-spiking parvalbumin (PV) GABAergic interneurons regulating pyramidal neuron activity drive appropriate behavioral responses. Further, their function is heavily diminished PFC numerous psychiatric diseases, schizophrenia autism. Previous research demonstrated importance optimal balance excitation inhibition (E/I) circuits maintaining efficiency information processing. Although we are still unraveling mechanisms representation cortex (PFC), E/I seems be crucial, as pharmacological, chemogenetic, optogenetic approaches for disrupting induce impairments range PFC-dependent behaviors. In this review, will explore two key hypotheses. First, PV powerful regulators PFC, help optimize processing supramodal PFC. Second, diminishing sufficient generate an elaborate symptom sequelae corresponding those observed diseases. Then, using framework, speculate on whether circuitry could represent platform development therapeutic interventions disorders function.

Language: Английский

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Thalamic regulation of switching between cortical representations enables cognitive flexibility

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(12), P. 1753 - 1763

Published: Nov. 8, 2018

Language: Английский

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Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(8), P. 1223 - 1234

Published: July 22, 2019

Language: Английский

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Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 445 - 465

Published: April 19, 2021

Language: Английский

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Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition

Neuroscience & Biobehavioral Reviews, Journal Year: 2019, Volume and Issue: 105, P. 39 - 51

Published: Aug. 1, 2019

Language: Английский

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A Disinhibitory Microcircuit Mediates Conditioned Social Fear in the Prefrontal Cortex

Neuron, Journal Year: 2019, Volume and Issue: 102(3), P. 668 - 682.e5

Published: March 18, 2019

Language: Английский

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Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 11, 2022

Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental which has strong genetic basis. Despite the rapidly rising incidence of autism, little known about its aetiology, risk factors, disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication autism. Over last two decades, there have been remarkable advances in genetics, with hundreds genes identified as being associated high The convergence neuroscience methods becoming more widely recognized significance elucidating pathological mechanisms Efforts devoted to exploring behavioural functions, key potential treatments Here, we highlight this review, emerging evidence shows that signal transduction molecular events involved processes such transcription, translation, synaptic transmission, epigenetics immunoinflammatory responses. This involvement important implications discovery precise targets Moreover, review recent insights into clinical autism from molecular, cellular, neural circuit, neurobehavioural aspects. Finally, challenges future perspectives discussed regard novel strategies predicated on biological features

Language: Английский

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Engagement of Pulvino-cortical Feedforward and Feedback Pathways in Cognitive Computations

Neuron, Journal Year: 2018, Volume and Issue: 101(2), P. 321 - 336.e9

Published: Dec. 12, 2018

Language: Английский

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PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: July 1, 2019

Abstract Postsynaptic density protein-95 (PSD-95) is a major regulator in the maturation of excitatory synapses by interacting and trafficking N-methyl-D-aspartic acid receptors (NMDAR) α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic (AMPAR) to postsynaptic membrane. PSD-95 disruption has recently been associated with neuropsychiatric disorders such as schizophrenia autism. However, effects deficiency on prefrontal cortex (PFC)-associated functions, including cognition, working memory, sociability, yet be investigated. Using knockout mouse model (PSD-95 −/− ), we examined how affects NMDAR AMPAR expression function medial (mPFC) during juvenile adolescent periods development. We found significant increases total protein levels subunits GluN1, GluN2B, accompanied decreases subunit GluA1 adolescence. Correspondingly, there increase NMDAR/AMPAR-mediated current amplitude ratio that progresses from juvenile-to-adolescence. Behaviorally, mice exhibit lack well learning memory deficits. Together, our data indicate disrupts mPFC synaptic related behavior at critical age This study highlights importance neurodevelopment its potential link pathogenesis and/or

Language: Английский

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Ventral Hippocampal-Prefrontal Interaction Affects Social Behavior via Parvalbumin Positive Neurons in the Medial Prefrontal Cortex

iScience, Journal Year: 2020, Volume and Issue: 23(3), P. 100894 - 100894

Published: Feb. 11, 2020

Ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) are both critical regions for social behaviors. However, how their interactions affect behavior is not well understood. By viral tracing, optogenetics, chemogenetics, fiber photometry, we demonstrated that inhibition of vHIP or direct projections from to mPFC impaired memory expression. Via rabies retrograde found all three major GABAergic neurons in received inputs vHIP. Activation parvalbumin positive (PV+) but somatostatin (SST+) can rescue the impairment caused by inhibition. Furthermore, photometry results behaviors preferentially recruited PV+ hippocampal disrupted activity during interactions. These revealed a new mechanism regulate complementarity with existing neural circuitry mechanism.

Language: Английский

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