Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction

Bukalo, Olena; Nonaka, Mio; Weinholtz, Chase A.; Mendez, Adriana; Taylor, William W.; Holmes, Andrew

doi:10.1016/j.bbr.2020.112913

Cited by 28 publications

(13 citation statements)

References 33 publications

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“…Furthermore, chronic stimulation of engram cells associated with fear memories in the hippocampus produced a reduction of fear responses, suggesting that optogenetic manipulation of a fear engram is sufficient to induce an extinction-like behavior ( Chen et al, 2019 ; Cincotta et al, 2021 ). Likewise, the inhibition of the assembly activated during cue-paired alcohol self-administration in the medial prefrontal cortex (mPFC), 1 month later prevented relapse of alcohol-seeking ( Visser et al, 2020 ), and optogenetic activation of infralimbic cortex-basolateral amygdala pathway during fear extinction trials, resulted in a stronger extinction compared to non-optogenetic activation ( Bukalo et al, 2021 ). From these data, it can be inferred that in fact extinction represents new learning that requires the formation of a new engram.…”

Section: Mechanisms Underlying Extinction: Hebbian and Homeostatic Plasticitymentioning

confidence: 99%

Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

Reyes-García

Escobar

2021

Front. Cell. Neurosci.

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In nature, animals need to adapt to constant changes in their environment. Learning and memory are cognitive capabilities that allow this to happen. Extinction, the reduction of a certain behavior or learning previously established, refers to a very particular and interesting type of learning that has been the basis of a series of therapies to diminish non-adaptive behaviors. In recent years, the exploration of the cellular and molecular mechanisms underlying this type of learning has received increasing attention. Hebbian plasticity (the activity-dependent modification of the strength or efficacy of synaptic transmission), and homeostatic plasticity (the homeostatic regulation of plasticity) constitute processes intimately associated with memory formation and maintenance. Particularly, long-term depression (LTD) has been proposed as the underlying mechanism of extinction, while the protein phosphatase calcineurin (CaN) has been widely related to both the extinction process and LTD. In this review, we focus on the available evidence that sustains CaN modulation of LTD and its association with extinction. Beyond the classic view, we also examine the interconnection among extinction, Hebbian and homeostatic plasticity, as well as emergent evidence of the participation of kinases and long-term potentiation (LTP) on extinction learning, highlighting the importance of the balance between kinases and phosphatases in the expression of extinction. Finally, we also integrate data that shows the association between extinction and less-studied phenomena, such as synaptic silencing and engram formation that open new perspectives in the field.

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Section: Mechanisms Underlying Extinction: Hebbian and Homeostatic Plasticitymentioning

confidence: 99%

Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

Reyes-García

Escobar

2021

Front. Cell. Neurosci.

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“…Moreover, previous findings indicate that stress can produce asymmetrical changes in the mPFC, and functional lateralization of mPFC affects emotional states following stress (Sullivan and Gratton, 1999;Cerqueira et al, 2008;Lee et al, 2015;Costa et al, 2016;Victoriano et al, 2020;Santos-Costa et al, 2021) and hemispheric asymmetry in volume of the hippocampus, amygdala, and cortex of PTSD patients has been reported (Adami et al, 2006;Karl et al, 2006;Morey et al, 2012;Zach et al, 2016;Cwik et al, 2020), suggesting that these SPSinduced changes may be lateralized. Previous studies have found that bilateral optogenetic stimulation of the IL or IL inputs to the basolateral amygdala during extinction training enhance extinction memories in rodents (Bukalo et al, 2015(Bukalo et al, , 2021Do-Monte et al, 2015). These studies have provided insights into the neural substrates of extinction learning and memory using animal models of conditioned fear and exposure.…”

Section: Introductionmentioning

confidence: 95%

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

Canto-de-Souza

Demetrovich

Plas

et al. 2021

Front. Behav. Neurosci.

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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.

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“…An increase in ghrelin level can eliminate fear and inhibit the recurrence of fear [ 17 ], and BChE can hydrolyze ghrelin [ 18 ]. Failure to eliminate fear is a hallmark of stress disorders and neuropsychiatric diseases [ 19 ]. BChE is involved in the metabolism of endocannabinoids [ 20 ], and endocannabinoids are negatively correlated with the development of post-traumatic stress disorder (PTSD) [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Fear Extinction Memory and Resistance to Age-Related Cognitive Decline in Butyrylcholinesterase Knockout Mice and (R)-Bambuterol Treated Mice

Liu

Cao

Yang

et al. 2021

Biology

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Butyrylcholinesterase (BChE) is detected in plaques preferentially in Alzheimer’s disease (AD) and may be associated with stress disorders. However, the physiological function of BChE in the central nervous system remains to be further investigated. BChE knockout (KO) mice and wild-type (WT) mice with orally or intranasal administration of (R)-bambuterol were used to explore the effect of BChE on behavior changes. (R)-bambuterol is a specific and reversible inhibitor of BChE. The behavior changes were evaluated and compared among 3–10 month old mice. Our finding showed that BChE KO and (R)-bambuterol administration enhanced episodic memory, including fear conditioning memory and fear extinction memory in fear conditioning and fear extinction test. BChE KO and (R)-bambuterol administered mice rescued age-related spatial memory and general activity in the water maze test and open field test. The brain metabolomics were imaged using a desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The image of DESI-MS demonstrated that glutamine content increased in the brain of BChE KO mice. In conclusion, this study found that inhibition of BChE ameliorated episodic and spatial memories. This study also suggested that (R)-bambuterol as a BChE inhibitor has the potential application in the treatment of post-traumatic stress disorder (PTSD) and early cognitive decline.

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Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction

Cited by 28 publications

References 33 publications

Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

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

Enhancement of Fear Extinction Memory and Resistance to Age-Related Cognitive Decline in Butyrylcholinesterase Knockout Mice and (R)-Bambuterol Treated Mice

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