Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.
Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Tae
T
Kim
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Stephen
S
Thankachan
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
James T
JT
McKenna
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
James M
JM
McNally
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Chun
C
Yang
Center for Neuroscience, Korea Institute of Science and Technology, 130-722 Seoul, South Korea;
Jee Hyun
JH
Choi
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Lichao
L
Chen
Department of Psychiatry, Harvard Medical School, Boston, MA 02115; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02215; and.
Bernat
B
Kocsis
Departments of Psychiatry and Behavioral Sciences and Bioengineering, Stanford University, Stanford, CA 94305.
Karl
K
Deisseroth
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Robert E
RE
Strecker
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Radhika
R
Basheer
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115;
Ritchie E
http://orcid.org/0000-0002-7164-4132
RE
Brown
Department of Psychiatry, VA Boston Healthcare System, Brockton, MA 02301; Department of Psychiatry, Harvard Medical School, Boston, MA 02115; robert_mccarley@hms.harvard.edu.
Robert W
RW
McCarley
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D066187:Basal Forebrain / Q000502:physiology*; D000075402:Channelrhodopsins; D059329:Cholinergic Neurons / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000502:physiology; D065818:Gamma Rhythm / Q000502:physiology*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D010320:Parvalbumins / Q000378:metabolism*; D015203:Reproducibility of Results; D014161:Transduction, Genetic
D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; D010320:Parvalbumins; C054562:yellow fluorescent protein, Bacteria
ArchT; arousal; auditory steady-state response; channelrhodopsin2; optogenetics