A direct GABAergic output from the basal ganglia to frontal cortex.
The basal ganglia are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning. Current models postulate that the basal ganglia modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs, respectively). The basal ganglia thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the basal ganglia, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT(+) cells, which have been historically identified as an extension of the nucleus basalis, as well as ChAT(-) cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus, GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signalling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the basal ganglia to modulate frontal cortices.
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Arpiar
A
Saunders
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Ian A
IA
Oldenburg
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Vladimir K
VK
Berezovskii
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Caroline A
CA
Johnson
Neurobiology Imaging Facility, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nathan D
ND
Kingery
Image and Data Analysis Core, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Hunter L
HL
Elliott
Image and Data Analysis Core, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Tiao
T
Xie
Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Charles R
CR
Gerfen
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.
Bernardo L
BL
Sabatini
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D020532:Basal Nucleus of Meynert / Q000166:cytology / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D055724:Electrophysiological Phenomena; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009434:Neural Pathways; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine