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Cortical circuit dynamics during punishment‐resistant alcohol drinking
Author(s) -
Siciliano Cody A,
Leow Yi Ning,
Weele Caitlin Vander,
Kimchi Eyal,
Xu Derek,
Chen Xinhong,
Tye Kay M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.661.6
Subject(s) - prefrontal cortex , neuroscience , alcohol , nucleus accumbens , aversive stimulus , ethanol , saccharin , alcohol use disorder , periaqueductal gray , stimulus (psychology) , psychology , chemistry , dopamine , endocrinology , biology , central nervous system , cognition , midbrain , biochemistry , psychotherapist
A great deal of research has highlighted the role of the medial prefrontal cortex (mPFC) in encoding motivational value and decision making. Further, alcohol‐induced plasticity in mPFC has been implicated in aberrant alcohol drinking behaviors; however, we have little understanding of how neurons in mPFC are encoding alcohol related stimuli in real time, and what downstream circuits are involved. Here, we sought to dissect the role of projection‐defined subpopulations within mPFC in punishment resistant alcohol drinking. To allow for in vivo recordings of neural activity from defined populations, we delivered a Cre‐dependent viral vector carrying the genetically encoded calcium indicator GCaMP6m in the mPFC of male C57BL/6J mice. A second retrograde virus carrying Cre recombinase was injected into either the nucleus accumbens (NAc) or periaqueductal gray area (PAG) resulting in selective expression of the indicator in either mPFC:NAc or mPFC:PAG cells. By implanting a lens into the mPFC and attaching a miniature head‐mounted microscope we were then able to record calcium dynamics with single‐cell resolution during a Pavlovian conditioning task for alcohol, or alcohol adulterated with the bitter tastant quinine. We found that the activity of mPFC:PAG tracked stimulus value of both the conditioned and unconditioned stimulus throughout the course of alcohol and alcohol+quinine exposure. Indeed, mPFC:PAG cells were predominately inhibited by the presentation of an alcohol predictive cue, and during the consumption of alcohol. In animals that decreased their intake when quinine was present, mPFC:PAG showed excitation to the cue and during consumption, while animals that continued to drink despite quinine punishment continued to show an inhibitory response in this pathway. Additionally, we found that photostimulation of PFC‐PAG neurons produced robust avoidance, demonstrating a causal role for this pathway in encoding avoidance of aversive stimuli. Together, these results support a model where inhibition of the mPFC:PAG circuit encodes rewarding stimuli and promotes seeking, while activation encodes aversive stimuli and produces avoidance. Further, dysregulation of this pathway resulting from chronic alcohol use may blunt responsiveness to aversive stimuli and result in inflexible, punishment resistant alcohol drinking.