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  • 1
    Publication Date: 2011-07-01
    Description: The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775282/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stuber, Garret D -- Sparta, Dennis R -- Stamatakis, Alice M -- van Leeuwen, Wieke A -- Hardjoprajitno, Juanita E -- Cho, Saemi -- Tye, Kay M -- Kempadoo, Kimberly A -- Zhang, Feng -- Deisseroth, Karl -- Bonci, Antonello -- DA029325/DA/NIDA NIH HHS/ -- F32AA018610/AA/NIAAA NIH HHS/ -- R01 DA032750/DA/NIDA NIH HHS/ -- R21 DA029325/DA/NIDA NIH HHS/ -- England -- Nature. 2011 Jun 29;475(7356):377-80. doi: 10.1038/nature10194.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. gstuber@med.unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21716290" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology ; Animals ; Behavior, Addictive/physiopathology ; Cues ; Dopamine/metabolism ; Drinking ; Excitatory Postsynaptic Potentials/*physiology ; Glutamic Acid/metabolism ; Light ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Fibers/physiology ; Neural Pathways/*physiology ; Neurons/metabolism ; Nucleus Accumbens/cytology/*physiology ; Patch-Clamp Techniques ; Photic Stimulation ; Receptors, Dopamine D1/antagonists & inhibitors/metabolism ; *Reward ; Rhodopsin/genetics/metabolism ; Sucrose/metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-04-05
    Description: Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences. Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Billy T -- Yau, Hau-Jie -- Hatch, Christina -- Kusumoto-Yoshida, Ikue -- Cho, Saemi L -- Hopf, F Woodward -- Bonci, Antonello -- England -- Nature. 2013 Apr 18;496(7445):359-62. doi: 10.1038/nature12024. Epub 2013 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. billy.chen@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23552889" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Addictive/chemically induced/*physiopathology/therapy ; Cocaine/administration & dosage/*pharmacology ; Electroshock ; Limbic System/cytology/drug effects/physiology/physiopathology ; Male ; Optogenetics ; Photic Stimulation ; Prefrontal Cortex/drug effects/pathology/*physiology/*physiopathology ; Pyramidal Cells/cytology/drug effects/metabolism ; Rats ; Rats, Wistar ; Rhodopsin/metabolism ; Self Administration ; Stimulation, Chemical
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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