High-density electroencephalographic (hdEEG) recordings are widely used in human studies to determine spatio-temporal patterns of cortical electrical activity. How these patterns of activity are modulated by subcortical arousal systems is poorly understood. Here, we couple selective optogenetic stimulation of a defined subcortical cell-type, basal forebrain (BF) parvalbumin (PV) neurons, with hdEEG recordings in mice (Opto-hdEEG). Stimulation of BF PV projection neurons preferentially generated time-locked gamma oscillations in frontal cortices. BF PV gamma-frequency stimulation potently modulated an auditory sensory paradigm used to probe cortical function in neuropsychiatric disorders, the auditory steady-state response (ASSR). Phase-locked excitation of BF PV neurons in advance of 40 Hz auditory stimuli enhanced the power, precision and reliability of cortical responses, and the relationship between responses in frontal and auditory cortices. Furthermore, synchronization within a frontal hub and long-range cortical interactions were enhanced. Thus, phasic discharge of BF PV neurons changes cortical processing in a manner reminiscent of global workspace models of attention and consciousness.
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Berger H (1929) Ueber das elektroenkephalogramm des Menschen. Arch Psychiatr Nervenkr 87:527–570
Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087–1187
Burk JA, Sarter M (2001) Dissociation between the attentional functions mediated via basal forebrain cholinergic and GABAergic neurons. Neuroscience 105(4):899–909
Cardin JA, Carlen M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459(7247):663–667
Cardin JA, Carlen M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI (2010) Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nat Protoc 5(2):247–254. https://doi.org/10.1038/nprot.2009.228
Carlen M, Meletis K, Siegle JH, Cardin JA, Futai K, Vierling-Claassen D, Ruhlmann C, Jones SR, Deisseroth K, Sheng M, Moore CI, Tsai LH (2012) A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Mol Psychiatry 17:537–548
Choi JH, Koch KP, Poppendieck W, Lee M, Shin HS (2010) High resolution electroencephalography in freely moving mice. J Neurophysiol 104(3):1825–1834
Crone NE, Boatman D, Gordon B, Hao L (2001) Induced electrocorticographic gamma activity during auditory perception. Brazier Award-winning article, 2001. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 112(4):565–582
Dehaene S, Changeux JP (2011) Experimental and theoretical approaches to conscious processing. Neuron 70(2):200–227
Duque A, Balatoni B, Detari L, Zaborszky L (2000) EEG correlation of the discharge properties of identified neurons in the basal forebrain. J Neurophysiol 84(3):1627–1635
Franklin K, Paxinos G (2008) The mouse brain in stereotaxic coordinates, 3rd edn. Academic Press, North Ryde
Fries P (2009) Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci 32:209–224
Gray CM, Singer W (1989) Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex. Proc Natl Acad Sci USA 86(5):1698–1702
Gregoriou GG, Gotts SJ, Zhou H, Desimone R (2009) High-frequency, long-range coupling between prefrontal and visual cortex during attention. Science 324(5931):1207–1210
Gross J, Schmitz F, Schnitzler I, Kessler K, Shapiro K, Hommel B, Schnitzler A (2004) Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans. Proc Natl Acad Sci USA 101(35):13050–13055. https://doi.org/10.1073/pnas.0404944101
Hong LE, Summerfelt A, McMahon R, Adami H, Francis G, Elliott A, Buchanan RW, Thaker GK (2004) Evoked gamma band synchronization and the liability for schizophrenia. Schizophr Res 70(2–3):293–302. https://doi.org/10.1016/j.schres.2003.12.011
Kim T, Thankachan S, McKenna JT, McNally JM, Yang C, Choi JH, Chen L, Kocsis B, Deisseroth K, Strecker RE, Basheer R, Brown RE, McCarley RW (2015) Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations. Proc Natl Acad Sci USA 112(11):3535–3540
Kim H, Ahrlund-Richter S, Wang X, Deisseroth K, Carlen M (2016) Prefrontal parvalbumin neurons in control of attention. Cell 164(1–2):208–218. https://doi.org/10.1016/j.cell.2015.11.038
Kitzbichler MG, Henson RN, Smith ML, Nathan PJ, Bullmore ET (2011) Cognitive effort drives workspace configuration of human brain functional networks. J Neurosci 31(22):8259–8270. https://doi.org/10.1523/JNEUROSCI.0440-11.2011
Korotkova T, Fuchs EC, Ponomarenko A, von EJ, Monyer H (2010) NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial representations, and working memory. Neuron 68(3):557–569
Kwon JS, O’Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, Hasselmo ME, Potts GF, Shenton ME, McCarley RW (1999) Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Arch Gen Psychiatry 56(11):1001–1005
Lee M, Kim D, Shin HS, Sung HG, Choi JH (2011) High-density EEG recordings of the freely moving mice using polyimide-based microelectrode. J Vis Exp. https://doi.org/10.3791/2562
Lee C, Oostenveld R, Lee SH, Kim LH, Sung H, Choi JH (2013a) Cortical source localization of mouse extracranial electroencephalogram using the FieldTrip toolbox. Conf Proc IEEE Eng Med Biol Soc 2013:3307–3310. https://doi.org/10.1109/EMBC.2013.6610248
Lee C, Oostenveld R, Lee SH, Kim LH, Sung H, Choi JH (2013b) Dipole source localization of mouse electroencephalogram using the Fieldtrip toolbox. PLoS One 8(11):e79442. https://doi.org/10.1371/journal.pone.0079442
Lee JH, Kreitzer AC, Singer AC, Schiff ND (2017) Illuminating neural circuits: from molecules to MRI. J Neurosci 37(45):10817–10825. https://doi.org/10.1523/JNEUROSCI.2569-17.2017
Linden RD, Campbell KB, Hamel G, Picton TW (1985) Human auditory steady state evoked potentials during sleep. Ear Hear 6(3):167–174
McKenna JT, Yang C, Franciosi S, Winston S, Abarr KK, Rigby MS, Yanagawa Y, McCarley RW, Brown RE (2013) Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse. J Comp Neurol 521:1225–1250
Munk MH, Roelfsema PR, Konig P, Engel AK, Singer W (1996) Role of reticular activation in the modulation of intracortical synchronization. Science 272(5259):271–274
Nair J, Klaassen AL, Poirot J, Vyssotski A, Rasch B, Rainer G (2016) Gamma band directional interactions between basal forebrain and visual cortex during wake and sleep states. J Physiol Paris 110(1–2):19–28. https://doi.org/10.1016/j.jphysparis.2016.11.011
O’Donnell BF, Vohs JL, Krishnan GP, Rass O, Hetrick WP, Morzorati SL (2013) The auditory steady-state response (ASSR): a translational biomarker for schizophrenia. Suppl Clin Neurophysiol 62:101–112
Plourde G (1996) The effects of propofol on the 40-Hz auditory steady-state response and on the electroencephalogram in humans. Anesth Analg 82(5):1015–1022
Rosanova M, Casali A, Bellina V, Resta F, Mariotti M, Massimini M (2009) Natural frequencies of human corticothalamic circuits. J Neurosci 29(24):7679–7685
Schadow J, Lenz D, Dettler N, Frund I, Herrmann CS (2009) Early gamma-band responses reflect anticipatory top-down modulation in the auditory cortex. Neuroimage 47(2):651–658. https://doi.org/10.1016/j.neuroimage.2009.04.074
Skosnik PD, Krishnan GP, O’Donnell BF (2007) The effect of selective attention on the gamma-band auditory steady-state response. Neurosci Lett 420(3):223–228. https://doi.org/10.1016/j.neulet.2007.04.072
Sohal VS, Zhang F, Yizhar O, Deisseroth K (2009) Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459(7247):698–702
Spencer KM, Salisbury DF, Shenton ME, McCarley RW (2008) Gamma-band auditory steady-state responses are impaired in first episode psychosis. Biol Psychiatry 64(5):369–375
Spencer KM, Niznikiewicz MA, Nestor PG, Shenton ME, McCarley RW (2009) Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia. BMC Neurosci 10:85
Thanos PK, Robison L, Nestler EJ, Kim R, Michaelides M, Lobo MK, Volkow ND (2013) Mapping brain metabolic connectivity in awake rats with muPET and optogenetic stimulation. J Neurosci 33(15):6343–6349. https://doi.org/10.1523/JNEUROSCI.4997-12.2013
Thune H, Recasens M, Uhlhaas PJ (2016) The 40-Hz auditory steady-state response in patients with schizophrenia: a meta-analysis. JAMA Psychiatry 73(11):1145–1153. https://doi.org/10.1001/jamapsychiatry.2016.2619
Tiitinen H, Sinkkonen J, Reinikainen K, Alho K, Lavikainen J, Naatanen R (1993) Selective attention enhances the auditory 40-Hz transient response in humans. Nature 364(6432):59–60
Xu M, Chung S, Zhang S, Zhong P, Ma C, Chang WC, Weissbourd B, Sakai N, Luo L, Nishino S, Dan Y (2015) Basal forebrain circuit for sleep-wake control. Nat Neurosci 18(11):1641–1647. https://doi.org/10.1038/nn.4143
Yang C, Thankachan S, McCarley RW, Brown RE (2017) The menagerie of the basal forebrain: how many (neural) species are there, what do they look like, how do they behave and who talks to whom? Curr Opin Neurobiol 44:159–166. https://doi.org/10.1016/j.conb.2017.05.004
Zaborszky L, Csordas A, Mosca K, Kim J, Gielow MR, Vadasz C, Nadasdy Z (2013) Neurons in the basal forebrain project to the cortex in a complex topographic organization that reflects corticocortical connectivity patterns: an experimental study based on retrograde tracing and 3d reconstruction. Cereb Cortex. https://doi.org/10.1093/cercor/bht210
This work was performed at Korea Institute of Science and Technology and was supported in part by U.S. Veterans Administration, US National Institutes of Health Grant RO1 MH039683, the National Research Council of Science and technology of Korea (CRC-15-04-KIST) and the National Research Foundation of Korea (2017R1A2B3012659). REB and JTM received partial salary support from United States VA Biomedical Laboratory Research and Development Service Award I01BX001356. JMM is supported by VA CDA IK2BX002130. Additional salary support was provided by US National Institutes of Health Grants R01 MH100820, R21 NS079866 and R21 NS093000. REB, JTM and JMM are Research Health Scientists at VA Boston Healthcare System. The contents of this work do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. This work also reflects the intellectual contribution and mentorship of Prof. Robert W. McCarley, who sadly passed away during the final stages of this project.
Conflict of interest
The authors report no competing financial interests. JTM also received partial salary compensation and funding from Merck MISP (Merck Investigator Sponsored Programs) but has no conflict of interest with this work.
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Hwang, E., Brown, R.E., Kocsis, B. et al. Optogenetic stimulation of basal forebrain parvalbumin neurons modulates the cortical topography of auditory steady-state responses. Brain Struct Funct 224, 1505–1518 (2019). https://doi.org/10.1007/s00429-019-01845-5
- Basal forebrain
- Gamma oscillations
- Auditory steady-state response (ASSR)
- Optogenetic high-density EEG