Losing control: excessive alcohol seeking after selective inactivation of cue-responsive neurons in the infralimbic cortex
Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identifi...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 29, 2015
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| In: |
The journal of neuroscience
Year: 2015, Volume: 35, Issue: 30, Pages: 10750-10761 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.0684-15.2015 |
| Online Access: | Verlag, teilw. kostenfrei, Volltext: http://dx.doi.org/10.1523/JNEUROSCI.0684-15.2015 Verlag, teilw. kostenfrei, Volltext: http://www.jneurosci.org.ezproxy.medma.uni-heidelberg.de/content/35/30/10750 
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| Author Notes: | Simone Pfarr, Marcus W. Meinhardt, Manuela L. Klee, Anita C. Hansson, Valentina Vengeliene, Kai Schönig, Dusan Bartsch, Bruce T. Hope, Rainer Spanagel, and Wolfgang H. Sommer |
| Summary: | Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identified by their common expression of the activity marker cFos and comprised of both principal and interneurons. Here, we used cFos-lacZ and pCAG-lacZ transgenic rats for activity-dependent or nonselective inactivation of neurons, respectively, which by their lacZ encoded β-galactosidase activity convert the inactive prodrug Daun02 into the neurotoxin daunorubicin. We report that activity-dependent ablation of a neuronal ensemble in the infralimbic but not the prelimbic subregion induced excessive alcohol seeking. The targeted neuronal ensemble was specific for the cue-induced response because stress-induced reinstatement was not affected in these animals. Importantly, nonselective inactivation of infralimbic neurons, using pCAG-lacZ rats, was without functional consequence on the cue-induced reinstatement task. Thus, inhibitory control over alcohol seeking is exerted by distinct functional ensembles within the infralimbic cortex rather than by a general inhibitory tone of this region on the behavioral output. This indicates a high level of functional compartmentation within the rat mPFC whereat many functional ensembles could coexist and interact within the same subregion. |
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| Item Description: | Gesehen am 29.01.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.0684-15.2015 |