Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 396, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbr.2020.112913
Keywords
Basolateral amygdala; Infralimbic cortex; Prefrontal cortex; Fear; Extinction; Optogenetics; Channelrhodopsin-2
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Funding
- NIAAA Intramural Research Program
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The study investigates the role of the infralimbic cortex to basolateral amygdala pathway in fear extinction, finding that optogenetic stimulation of IL neurons projecting to BLA at different titers produces varying effects on extinction memory formation and fear suppression. This highlights the importance of the IL -> BLA pathway in fear regulation and emphasizes methodological factors in optogenetic studies of neural circuits underlying behavior.
Deficiencies in the ability to extinguish fear is a hallmark of Trauma- and stressor-related disorders, Anxiety disorders, and certain other neuropsychiatric conditions. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear is of significant translational relevance. Previous studies in rodents have shown that glutamatergic projections from the infralimbic prefrontal cortex (IL) to basolateral amygdala (BLA) play a crucial instructional role in the formation of extinction memories, and also indicate that variation in the strength of this input correlates with extinction efficacy. To further examine the relationship between the IL -> BLA pathway and extinction we expressed three different titers of the excitatory opsin, channelrhodopsin (ChR2), in IL neurons and photostimulated their projections in the BLA during partial extinction training. The behavioral effects of photoexcitation differed across the titer groups: the low titer had no effect, the medium titer selectively facilitated extinction memory formation, and the high titer produced both an acute suppression of fear and a decrease in fear during (light-free) extinction retrieval. We discuss various possible explanations for these titer-specific effects, including the possibility of IL-mediated inhibition of BLA fear-encoding neurons under conditions of sufficiently strong photoexcitation. These findings further support the role of IL -> BLA pathway in regulating fear and highlight the importance of methodological factors in optogenetic studies of neural circuits underling behavior.
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