scholarly journals Daily Optogenetic Stimulation of the Left Infralimbic Cortex Reverses Extinction Impairments in Male Rats Exposed to Single Prolonged Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Lucas Canto-de-Souza ◽  
Peyton G. Demetrovich ◽  
Samantha Plas ◽  
Rimenez R. Souza ◽  
Joseph Epperson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Incubation Period ◽  
Conditioned Fear ◽  
Male Rats ◽  
Traumatic Experiences ◽  
Post Traumatic Stress ◽  
Single Prolonged Stress ◽  
Optogenetic Stimulation ◽  
Prolonged Stress ◽  
Stimulation Of

Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cortex. PTSD-like pathophysiology and behaviors have been observed in rodents exposed to a single prolonged stress (SPS) procedure. When animals are left alone for 7 days after SPS treatment, they show increased anxiety-like behavior and impaired extinction of conditioned fear, and reduced activity in the prefrontal cortex. Here, we tested the hypothesis that daily optogenetic stimulation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) during the 7 days after SPS would reverse SPS effects on anxiety and fear extinction. Male Sprague-Dawley rats underwent SPS and then received daily optogenetic stimulation (20 Hz, 2 s trains, every 10 s for 15 min/day) of glutamatergic neurons of the left or right IL for seven days. After this incubation period, rats were tested in the elevated plus-maze (EPM). Twenty-four hours after the EPM test, rats underwent auditory fear conditioning (AFC), extinction training and a retention test. SPS increased anxiety-like behavior in the EPM task and produced a profound impairment in extinction of AFC. Optogenetic stimulation of the left IL, but not right, during the 7-day incubation period reversed the extinction impairment. Optogenetic stimulation did not reverse the increased anxiety-like behavior, suggesting that the extinction effects are not due to a treatment-induced reduction in anxiety. Results indicate that increased activity of the left IL after traumatic experiences can prevent development of extinction impairments. These findings suggest that non-invasive brain stimulation may be a useful tool for preventing maladaptive responses to trauma.

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

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.

scholarly journals An Advanced Transcriptional Response to Corticosterone After Single Prolonged Stress in Male Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Jinlan Ding ◽  
Xinzhao Chen ◽  
Fang Han ◽  
Onno C. Meijer
Keyword(s):  
Negative Feedback ◽  
Target Genes ◽  
Dorsal Hippocampus ◽  
Rapid Change ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Post Traumatic Stress ◽  
Transcriptional Responses ◽  
Single Prolonged Stress ◽  
Prolonged Stress

Stress-related neuropsychiatric disorders are often accompanied by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. In patients suffering from post-traumatic stress disorder (PTSD), increased sensitivity of glucocorticoid negative feedback has regularly been observed. The single prolonged stress (SPS) paradigm was developed to model increased negative feedback and other aspects of PTSD in rats. In this study, we used a setup that precluded the evaluation of negative feedback but rather served to test the hypothesis of the enhanced glucocorticoid receptor (GR) signaling in higher brain areas. We injected corticosterone or vehicle 7 days after SPS and evaluated plasma corticosterone, as well as gene expression in the dorsal hippocampus and amygdala. We observed a strikingly rapid change in the expression of established GR target genes (t = 30 min) only in the SPS group on exogenous corticosterone injection. Our results extend the notion of increased GR sensitivity in PTSD to include transcriptional responses in the hippocampus.

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

102 Single-Prolonged Stress as a Model of PTSD in Mice: Effects on Sleep and Anxiety

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A42-A42
Author(s):  
Katelyn Gutowsky ◽  
Carolyn Jones ◽  
Miranda Lim
Keyword(s):  
Rem Sleep ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Power Spectra ◽  
Post Traumatic Stress ◽  
Sleep State ◽  
Single Prolonged Stress ◽  
Post Traumatic ◽  
And Control ◽  
Prolonged Stress

Abstract Introduction Sleep problems are common in humans with post-traumatic stress disorder (PTSD). Rapid eye movement (REM) sleep is involved in processing emotional memories; it is often disrupted in those with PTSD, and may be related to increased anxiety. Single prolonged stress (SPS) is a protocol used to model PTSD in rats, however little is known about how this model impacts sleep in mice. Prior research suggests SPS produces short term disturbances in REM sleep and increases in anxiety-like behavior, but further validation of this model is needed to understand how SPS impacts sleep and anxiety-like behaviors in mice specifically, as they have greater potential for transgenic manipulation Methods C57BL6/J mice underwent a SPS protocol in which they were tube-restrained for 2 hours, followed by a 15 minute forced swim in a group, ether exposure until loss of consciousness, and 10 days of social isolation. Following SPS, mice were tested for anxiety-like behavior in a light-dark box and sleep was measured from surgically implanted EEG and EMG leads. Time spent in wake, REM sleep, and non-REM sleep was quantified for 24 continuous hours in SPS and Control mice. Results There were no significant effects of SPS on the amount of time spent in any vigilance state, or in sleep-wake transitions. However, SPS-exposed mice showed significantly more anxiety-like behavior. EEG power spectra were analyzed in relevant frequency bands during each sleep state, and exploratory analyses were conducted Conclusion Minimal effects on sleep macroarchitecture were seen in mice 10 days after SPS. It is possible that sleep disturbances seen immediately after trauma exposure (such as in prior studies in rats) may have diminished over time. Further studies will need to include additional timepoints and analysis of sleep microarchitecture following SPS, and in other mouse models of PTSD, in order to more comprehensively examine changes in sleep. Support (if any) VA CDA #IK2 BX002712, Portland VA Research Foundation, Medical Research Foundation

scholarly journals Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex

2010 ◽  
Vol 30 (48) ◽  
pp. 16082-16090 ◽  
Author(s):  
H. E. Covington ◽  
M. K. Lobo ◽  
I. Maze ◽  
V. Vialou ◽  
J. M. Hyman ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Antidepressant Effect ◽  
Optogenetic Stimulation ◽  
Stimulation Of
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