Original Article

Neuropsychopharmacology (2016) 41, 1014–1023; doi:10.1038/npp.2015.229; published online 26 August 2015

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

Hiroyuki Koike1,2,3,4,5, Michael P Demars1,2,3,4,5, Jennifer A Short1,2,3,4,5, Elisa M Nabel1,2,3,4,5, Schahram Akbarian1,2,5, Mark G Baxter2,5 and Hirofumi Morishita1,2,3,4,5

  1. 1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  2. 2Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  3. 3Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  4. 4Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  5. 5Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Correspondence: Professor H Morishita, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029, USA, Tel: +1 212 824 8975, Fax: +1 646 537 9584, E-mail: hirofumi.morishita@mssm.edu

Received 22 May 2015; Revised 25 July 2015; Accepted 28 July 2015
Accepted article preview online 30 July 2015; Advance online publication 26 August 2015

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Abstract

Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species.

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