Medial prefrontal D1 dopamine neurons control food intake.
Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and optogenetic photostimulation of D1 neurons increases feeding. Conversely, inhibition of D1 neurons decreases intake. Stimulation-based mapping of prefrontal D1 neuron projections implicates the medial basolateral amygdala (mBLA) as a downstream target of these afferents. mBLA neurons activated by prefrontal D1 stimulation are CaMKII positive and closely juxtaposed to prefrontal D1 axon terminals. Finally, photostimulating these axons in the mBLA is sufficient to increase feeding, recapitulating the effects of mPFC D1 stimulation. These data describe a new circuit for top-down control of food intake.
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Benjamin B
BB
Land
1] Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Nandakumar S
NS
Narayanan
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Rong-Jian
RJ
Liu
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Carol A
CA
Gianessi
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Catherine E
CE
Brayton
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
David M
DM
Grimaldi
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Maysa
M
Sarhan
1] Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA. [2] Present address: Department of Biology, Colgate University, Hamilton, New York, USA.
Douglas J
DJ
Guarnieri
1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Karl
K
Deisseroth
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
George K
GK
Aghajanian
Department of Psychiatry and Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA.
Ralph J
RJ
DiLeone
D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D004435:Eating / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000235:genetics; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics / Q000528:radiation effects; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000009:adverse effects; D017397:Prefrontal Cortex / Q000166:cytology*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000075402:Channelrhodopsins; C583261:Drd1 protein, mouse; D008164:Luminescent Proteins; D017447:Receptors, Dopamine D1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2