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  • 1
    Publication Date: 2013-12-21
    Description: The inbred mouse C57BL/6J is the reference strain for genome sequence and for most behavioral and physiological phenotypes. However, the International Knockout Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N substrain. We found that C57BL/6N has a lower acute and sensitized response to cocaine and methamphetamine. We mapped a single causative locus and identified a nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key regulator of cocaine response in mammals and present a framework to use mouse substrains to identify previously unknown genes and alleles regulating behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500108/" 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/PMC4500108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Vivek -- Kim, Kyungin -- Joseph, Chryshanthi -- Kourrich, Said -- Yoo, Seung-Hee -- Huang, Hung Chung -- Vitaterna, Martha H -- de Villena, Fernando Pardo-Manuel -- Churchill, Gary -- Bonci, Antonello -- Takahashi, Joseph S -- F32 DA024556/DA/NIDA NIH HHS/ -- F32DA024556/DA/NIDA NIH HHS/ -- U01 MH061915/MH/NIMH NIH HHS/ -- U01MH61915/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1508-12. doi: 10.1126/science.1245503.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357318" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Central Nervous System Stimulants/administration & dosage ; Cocaine/*administration & dosage ; Cocaine-Related Disorders/*genetics/*psychology ; *Drug-Seeking Behavior ; Methamphetamine/administration & dosage ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Mutation ; Nerve Tissue Proteins/genetics/*physiology ; Phenylalanine/genetics ; Polymorphism, Single Nucleotide ; Psychomotor Performance/drug effects ; Quantitative Trait Loci ; Serine/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    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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  • 3
    Publication Date: 2009-04-25
    Description: Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are known to fire action potentials tonically or phasically under different behavioral conditions. However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. We used optogenetic tools to selectively stimulate VTA dopaminergic neuron action potential firing in freely behaving mammals. We found that phasic activation of these neurons was sufficient to drive behavioral conditioning and elicited dopamine transients with magnitudes not achieved by longer, lower-frequency spiking. These results demonstrate that phasic dopaminergic activity is sufficient to mediate mammalian behavioral conditioning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Hsing-Chen -- Zhang, Feng -- Adamantidis, Antoine -- Stuber, Garret D -- Bonci, Antonello -- de Lecea, Luis -- Deisseroth, Karl -- K99 NS065009/NS/NINDS NIH HHS/ -- R01 DA021880/DA/NIDA NIH HHS/ -- R01 MH087592/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 May 22;324(5930):1080-4. doi: 10.1126/science.1168878. Epub 2009 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Program, W080 Clark Center, 318 Campus Drive West, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19389999" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; *Behavior, Animal ; *Conditioning (Psychology) ; Dopamine/*metabolism ; Electrodes, Implanted ; Genetic Vectors ; Light ; Mice ; Mice, Transgenic ; Neurons/*physiology ; Patch-Clamp Techniques ; Reward ; Rhodopsin/genetics ; Transduction, Genetic ; Ventral Tegmental Area/cytology/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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