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  • 1
    Publication Date: 2015-01-28
    Description: Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2008-05-13
    Description: What neural changes underlie individual differences in goal-directed learning? The lateral amygdala (LA) is important for assigning emotional and motivational significance to discrete environmental cues, including those that signal rewarding events. Recognizing that a cue predicts a reward enhances an animal's ability to acquire that reward; however, the cellular and synaptic mechanisms that underlie cue-reward learning are unclear. Here we show that marked changes in both cue-induced neuronal firing and input-specific synaptic strength occur with the successful acquisition of a cue-reward association within a single training session. We performed both in vivo and ex vivo electrophysiological recordings in the LA of rats trained to self-administer sucrose. We observed that reward-learning success increased in proportion to the number of amygdala neurons that responded phasically to a reward-predictive cue. Furthermore, cue-reward learning induced an AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated increase in the strength of thalamic, but not cortical, synapses in the LA that was apparent immediately after the first training session. The level of learning attained by individual subjects was highly correlated with the degree of synaptic strength enhancement. Importantly, intra-LA NMDA (N-methyl-d-aspartate)-receptor blockade impaired reward-learning performance and attenuated the associated increase in synaptic strength. These findings provide evidence of a connection between LA synaptic plasticity and cue-reward learning, potentially representing a key mechanism underlying goal-directed behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759353/" 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/PMC2759353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tye, Kay M -- Stuber, Garret D -- de Ridder, Bram -- Bonci, Antonello -- Janak, Patricia H -- R01 DA015096/DA/NIDA NIH HHS/ -- R01 DA015096-06/DA/NIDA NIH HHS/ -- R01DA115096/DA/NIDA NIH HHS/ -- England -- Nature. 2008 Jun 26;453(7199):1253-7. doi: 10.1038/nature06963. Epub 2008 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18469802" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*cytology/physiology ; Animals ; *Cues ; Excitatory Postsynaptic Potentials ; Learning/*physiology ; Male ; Models, Neurological ; N-Methylaspartate/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; *Reward ; Synapses/*metabolism ; Thalamus/*cytology/physiology
    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: 2008-09-20
    Description: Using sensory information for the prediction of future events is essential for survival. Midbrain dopamine neurons are activated by environmental cues that predict rewards, but the cellular mechanisms that underlie this phenomenon remain elusive. We used in vivo voltammetry and in vitro patch-clamp electrophysiology to show that both dopamine release to reward predictive cues and enhanced synaptic strength onto dopamine neurons develop over the course of cue-reward learning. Increased synaptic strength was not observed after stable behavioral responding. Thus, enhanced synaptic strength onto dopamine neurons may act to facilitate the transformation of neutral environmental stimuli to salient reward-predictive cues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613864/" 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/PMC2613864/" 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 -- Klanker, Marianne -- de Ridder, Bram -- Bowers, M Scott -- Joosten, Ruud N -- Feenstra, Matthijs G -- Bonci, Antonello -- DA015096/DA/NIDA NIH HHS/ -- DA021937/DA/NIDA NIH HHS/ -- R01 DA015096/DA/NIDA NIH HHS/ -- R01 DA015096-06/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 19;321(5896):1690-2. doi: 10.1126/science.1160873.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA 94608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18802002" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning (Psychology) ; Cues ; Dopamine/*physiology ; Excitatory Postsynaptic Potentials ; *Learning ; Long-Term Potentiation ; Male ; Mesencephalon/cytology/*physiology ; Neurons/*physiology ; Nucleus Accumbens/*physiology ; Patch-Clamp Techniques ; Rats ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; *Reward ; Signal Transduction ; Synapses/*physiology ; Synaptic Transmission
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    Publication Date: 2008-08-21
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
  • 10
    Publication Date: 2009-04-02
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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