Single Prolonged Stress Reduces Intrinsic Excitability and Excitatory Synaptic Drive onto Pyramidal Neurons in the Infralimbic Prefrontal Cortex of Adult Rats

ABSTRACTPost-traumatic stress disorder (PTSD) is a chronic, debilitating mental illness marked by abnormal fear responses and deficits in extinction of fear memories. The pathophysiology of PTSD is linked to decreased activation of the ventromedial prefrontal cortex (vmPFC). This study aims to investigate underlying functional changes in synaptic drive and intrinsic excitability of pyramidal neurons in the rodent homolog of the vmPFC, the infralimbic cortex (IL), following exposure to single prolonged stress (SPS), a paradigm that mimics core symptoms of PTSD in rats. Rats were exposed to SPS and allowed one week of recovery following which brain slices containing the PFC were prepared for whole-cell patch clamp recordings from layer V pyramidal neurons in the IL. Our results indicate that SPS reduces spontaneous excitatory synaptic drive to pyramidal neurons. In addition, SPS decreases the intrinsic membrane excitability of IL PFC pyramidal cells, as indicated by an increase in rheobase, decrease in input resistance, hyperpolarization of resting membrane potential, and a reduction in repetitive firing rate. Our results suggest that SPS causes a lasting reduction in PFC activity, supporting a body of evidence linking traumatic stress with prefrontal hypoactivity.Graphical AbstractSPS causes a decrease in excitatory synaptic drive and intrinsic excitability of IL pyramidal neurons.

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Single Prolonged Stress Reduces Intrinsic Excitability and Excitatory Synaptic Drive Onto Pyramidal Neurons in the Infralimbic Prefrontal Cortex of Adult Male Rats

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.705660 ◽

2021 ◽

Vol 15 ◽

Author(s):

Nawshaba Nawreen ◽

Mark L. Baccei ◽

James P. Herman

Keyword(s):

Prefrontal Cortex ◽

Traumatic Stress ◽

Pyramidal Neurons ◽

Male Rats ◽

Intrinsic Excitability ◽

Repetitive Firing ◽

Membrane Excitability ◽

Single Prolonged Stress ◽

Prolonged Stress ◽

Synaptic Drive

Post-traumatic stress disorder (PTSD) is a chronic, debilitating mental illness marked by abnormal fear responses and deficits in extinction of fear memories. The pathophysiology of PTSD is linked to decreased activation of the ventromedial prefrontal cortex (vmPFC). This study aims to investigate underlying functional changes in synaptic drive and intrinsic excitability of pyramidal neurons in the rodent homolog of the vmPFC, the infralimbic cortex (IL), following exposure to single prolonged stress (SPS), a paradigm that mimics core symptoms of PTSD in rats. Rats were exposed to SPS and allowed 1 week of recovery, following which brain slices containing the PFC were prepared for whole-cell patch clamp recordings from layer V pyramidal neurons in the IL. Our results indicate that SPS reduces spontaneous excitatory synaptic drive to pyramidal neurons. In addition, SPS decreases the intrinsic membrane excitability of IL PFC pyramidal cells, as indicated by an increase in rheobase, decrease in input resistance, hyperpolarization of resting membrane potential, and a reduction in repetitive firing rate. Our results suggest that SPS causes a lasting reduction in PFC activity, supporting a body of evidence linking traumatic stress with prefrontal hypoactivity.

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Genistein Prevents Single Prolonged Stress-Induced Cognitive Impairment in a Post-Traumatic Stress Disorder Rat Model via Activation of the Serotonergic System

Journal of Medicinal Food ◽

10.1089/jmf.2019.4519 ◽

2020 ◽

Vol 23 (5) ◽

pp. 476-484

Author(s):

Bombi Lee ◽

Gwang Muk Choi ◽

Insop Shim ◽

Hyejung Lee

Keyword(s):

Cognitive Impairment ◽

Rat Model ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Serotonergic System ◽

Post Traumatic Stress ◽

Single Prolonged Stress ◽

Post Traumatic ◽

Prolonged Stress

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Developmental Regulation of Basket Interneuron Synapses and Behavior through NCAM in Mouse Prefrontal Cortex

Cerebral Cortex ◽

10.1093/cercor/bhaa074 ◽

2020 ◽

Vol 30 (8) ◽

pp. 4689-4707

Author(s):

Chelsea S Sullivan ◽

Vishwa Mohan ◽

Paul B Manis ◽

Sheryl S Moy ◽

Young Truong ◽

...

Keyword(s):

Prefrontal Cortex ◽

Pyramidal Neurons ◽

Developmental Regulation ◽

Brain Slices ◽

Pyramidal Cells ◽

Electrophysiological Recording ◽

Network Function ◽

Growth Cone Collapse ◽

Layer 2 ◽

And Behavior

Abstract Parvalbumin (PV)-expressing basket interneurons in the prefrontal cortex (PFC) regulate pyramidal cell firing, synchrony, and network oscillations. Yet, it is unclear how their perisomatic inputs to pyramidal neurons are integrated into neural circuitry and adjusted postnatally. Neural cell adhesion molecule NCAM is expressed in a variety of cells in the PFC and cooperates with EphrinA/EphAs to regulate inhibitory synapse density. Here, analysis of a novel parvalbumin (PV)-Cre: NCAM F/F mouse mutant revealed that NCAM functions presynaptically in PV+ basket interneurons to regulate postnatal elimination of perisomatic synapses. Mutant mice exhibited an increased density of PV+ perisomatic puncta in PFC layer 2/3, while live imaging in mutant brain slices revealed fewer puncta that were dynamically eliminated. Furthermore, EphrinA5-induced growth cone collapse in PV+ interneurons in culture depended on NCAM expression. Electrophysiological recording from layer 2/3 pyramidal cells in mutant PFC slices showed a slower rise time of inhibitory synaptic currents. PV-Cre: NCAM F/F mice exhibited impairments in working memory and social behavior that may be impacted by altered PFC circuitry. These findings suggest that the density of perisomatic synapses of PV+ basket interneurons is regulated postnatally by NCAM, likely through EphrinA-dependent elimination, which is important for appropriate PFC network function and behavior.

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