Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex.
Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.
Department of Pharmacology, ‡Vanderbilt Brain Institute, §Vanderbilt Kennedy Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
Devon L
DL
Graham
Heather H
HH
Durai
Jamie D
JD
Garden
Evan L
EL
Cohen
Franklin D
FD
Echevarria
Gregg D
GD
Stanwood
D000818:Animals; D002452:Cell Count; D003863:Depression / Q000378:metabolism / Q000473:pathology; D004644:Emotions / Q000502:physiology; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006179:Gyrus Cinguli / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D010320:Parvalbumins / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000235:genetics
C000600618:DRD2 protein, mouse; D010320:Parvalbumins; D017448:Receptors, Dopamine D2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
Drd2-eGFP; GABA; Inhibitory; depression; knockout; parvalbumin