Analyses of ancient dog DNA suggest that dogs were likely domesticated from Eurasian wolves around 23,000 years ago, possibly in Siberia.
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Edited by Nancy Kopell, Boston University, Boston, MA, and approved February 2, 2015 (received for review July 17, 2014)
Significance
When we are awake, purposeful thinking and behavior require the synchronization of brain cells involved in different aspects of the same task. Cerebral cortex electrical oscillations in the gamma (30–80 Hz) range are particularly important in such synchronization. In this report we identify a particular subcortical cell type which has increased activity during waking and is involved in activating the cerebral cortex and generating gamma oscillations, enabling active cortical processing. Abnormalities of the brain mechanisms controlling gamma oscillations are involved in the disordered thinking typical of neuropsychiatric disorders such as schizophrenia. Thus, these findings may pave the way for targeted therapies to treat schizophrenia and other disorders involving abnormal cortical gamma oscillations.
Abstract
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.
Footnotes
↵1Present address: Department of Psychiatry, Kyung Hee University Hospital at Gangdong, 134-727 Seoul, Korea.
↵2T.K. and S.T. contributed equally to this work.
↵3R.E.B. and R.W.M. contributed equally to this work.
- ↵4To whom correspondence should be addressed. Email: robert_mccarley{at}hms.harvard.edu.
Author contributions: T.K., S.T., J.T.M., J.M.M., C.Y., R.E.S., R.B., R.E.B., and R.W.M. designed research; T.K., S.T., J.T.M., J.M.M., C.Y., L.C., and R.B. performed research; K.D. contributed new reagents/analytic tools; T.K., S.T., J.T.M., J.M.M., C.Y., J.H.C., B.K., R.E.S., R.B., R.E.B., and R.W.M. analyzed data; and T.K., S.T., J.T.M., J.M.M., C.Y., B.K., R.E.S., R.B., R.E.B., and R.W.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1413625112/-/DCSupplemental.
Freely available online through the PNAS open access option.
Basal forebrain parvalbumin neurons and EEG gamma
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