title: Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.
abstract: During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Sellers
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
authors.forename: Davis V
authors.initials: DV
authors.lastname: Bennett
authors.affiliation: INRIA CR Nancy-Grand Est, Team Neurosys, Villers-les-Nancy, France;
authors.forename: Axel
authors.initials: A
authors.lastname: Hutt
authors.affiliation: Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
authors.forename: James H
authors.initials: JH
authors.lastname: Williams
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina flavio_frohlich@med.unc.edu.
authors.forename: Flavio
authors.initials: F
authors.lastname: Fröhlich
mesh_terms: D000161:Acoustic Stimulation; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D005289:Ferrets; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000502:physiology*; D013057:Spectrum Analysis; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
keywords: anesthesia; ferret; frequency structure; isoflurane; prefrontal cortex
references.citation: Neuroscientist. 2011 Feb;17(1):94-106
references.pmid: 21343409
references.citation: J Neurosci. 1996 Jul 1;16(13):4240-9
references.pmid: 8753885
references.citation: Eur J Neurosci. 2010 Sep;32(5):786-97
references.pmid: 20646050
references.citation: J Physiol. 1977 Jun;268(2):391-421
references.pmid: 874916
references.citation: Nat Neurosci. 2008 Jul;11(7):749-51
references.pmid: 18552841
references.citation: Stat Med. 2008 Jul 10;27(15):2922-47
references.pmid: 18076131
references.citation: J Neurosci. 2013 Oct 30;33(44):17373-84
references.pmid: 24174670
references.citation: Anesthesiology. 1998 Jun;88(6):1592-605
references.pmid: 9637654
references.citation: Eur J Neurosci. 2005 Jan;21(1):93-102
references.pmid: 15654846
references.citation: Brain Res. 2013 Jul 19;1522:38-58
references.pmid: 23665053
references.citation: N Engl J Med. 2010 Dec 30;363(27):2638-50
references.pmid: 21190458
references.citation: Anesthesiology. 2013 Nov;119(5):1003-5
references.pmid: 23962968
references.citation: Science. 2001 Feb 23;291(5508):1560-3
references.pmid: 11222864
references.citation: Brain Res. 1990 Apr 30;514(2):276-92
references.pmid: 2357542
references.citation: Anesthesiology. 2013 Jun;118(6):1264-75
references.pmid: 23695090
references.citation: J Neurosci. 2009 May 6;29(18):5897-909
references.pmid: 19420256
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):E3377-86
references.pmid: 23129622
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16976-81
references.pmid: 20837521
references.citation: Neural Netw. 2009 Oct;22(8):1071-8
references.pmid: 19632814
references.citation: J Neurosci. 2006 Jan 11;26(2):448-57
references.pmid: 16407542
references.citation: Electroencephalogr Clin Neurophysiol. 1949 Feb;1(1):45-51
references.pmid: 18129182
references.citation: Spat Vis. 1997;10(4):433-6
references.pmid: 9176952
references.citation: Anesthesiology. 2004 Feb;100(2):428-33
references.pmid: 14739820
references.citation: Nat Neurosci. 2008 May;11(5):535-7
references.pmid: 18376400
references.citation: Front Syst Neurosci. 2014 Oct 07;8:191
references.pmid: 25339873
references.citation: Nat Neurosci. 2003 Nov;6(11):1216-23
references.pmid: 14583754
references.citation: Ann N Y Acad Sci. 2009 Mar;1157:61-70
references.pmid: 19351356
references.citation: J Neurophysiol. 2013 Dec;110(12):2739-51
references.pmid: 24047911
references.citation: Nature. 2013 Jan 3;493(7430):97-100
references.pmid: 23172139
references.citation: Neuron. 2001 Nov 8;32(3):503-14
references.pmid: 11709160
references.citation: Brain Res. 1999 May 22;829(1-2):77-89
references.pmid: 10350532
references.citation: J Neurosci Methods. 2007 May 15;162(1-2):49-63
references.pmid: 17292478
references.citation: Br J Anaesth. 1991 Jan;66(1):81-7
references.pmid: 1997064
references.citation: J Neurophysiol. 2009 Oct;102(4):2096-111
references.pmid: 19657080
references.citation: Conscious Cogn. 2001 Jun;10(2):165-83
references.pmid: 11414713
references.citation: J Neurosci. 2014 Jul 23;34(30):10122-33
references.pmid: 25057213
references.citation: Science. 2008 Nov 7;322(5903):876-80
references.pmid: 18988836
references.citation: J Neurosci. 2006 Apr 26;26(17):4535-45
references.pmid: 16641233
references.citation: Neuropharmacology. 2012 Aug;63(2):266-73
references.pmid: 22491022
references.citation: J Cogn Neurosci. 2011 Jun;23(6):1507-21
references.pmid: 20695762
references.citation: Nature. 2003 May 15;423(6937):288-93
references.pmid: 12748642
references.citation: Nat Neurosci. 1999 May;2(5):422-6
references.pmid: 10321245
references.citation: Eur J Neurosci. 2002 Feb;15(4):744-52
references.pmid: 11886439
references.citation: Annu Rev Neurosci. 2011;34:601-28
references.pmid: 21513454
references.citation: J Neurosci. 2007 May 16;27(20):5280-90
references.pmid: 17507551
references.citation: Br J Anaesth. 1986 Jun;58(6):580-5
references.pmid: 3707793
references.citation: Anesthesiology. 2001 Jun;94(6):973-81
references.pmid: 11465623
references.citation: Neurosci Lett. 2008 Feb 6;431(3):191-6
references.pmid: 18178313
references.citation: J Neurosci Methods. 2003 Oct 15;129(1):19-31
references.pmid: 12951229
references.citation: Anesthesiology. 2005 May;102(5):937-47
references.pmid: 15851880
references.citation: Science. 2007 Mar 30;315(5820):1860-2
references.pmid: 17395832
references.citation: Br J Anaesth. 2002 Jul;89(1):112-22
references.pmid: 12173224
references.citation: J Neurophysiol. 1999 Jun;81(6):3021-33
references.pmid: 10368417
references.citation: Anesthesiology. 2013 Nov;119(5):1031-42
references.pmid: 23969561
references.citation: J Comp Neurol. 2005 Jul 4;487(3):312-31
references.pmid: 15892103
references.citation: Anesthesiology. 1998 Mar;88(3):642-50
references.pmid: 9523807
references.citation: Anesthesiology. 1998 Oct;89(4):980-1002
references.pmid: 9778016
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3263-8
references.pmid: 9501251
references.citation: Nat Neurosci. 2012 Apr;15(4):537-9
references.pmid: 22406552
references.citation: J Neurosci Methods. 2001 Mar 30;106(1):69-79
references.pmid: 11248342
references.citation: Comp Med. 2008 Oct;58(5):454-7
references.pmid: 19004371
references.citation: Nat Rev Neurosci. 2004 Sep;5(9):709-20
references.pmid: 15322529
references.citation: Cereb Cortex. 2009 Oct;19(10):2466-78
references.pmid: 19211660
references.citation: Nat Neurosci. 2001 Nov;4(11):1131-8
references.pmid: 11593234
references.citation: Nature. 2001 Dec 20-27;414(6866):905-8
references.pmid: 11780062
references.citation: Arch Ital Biol. 2012 Jun-Sep;150(2-3):155-63
references.pmid: 23165875
references.citation: J Neurophysiol. 2011 Aug;106(2):500-14
references.pmid: 21543752
references.citation: Nat Neurosci. 2010 Aug;13(8):1011-9
references.pmid: 20622871
references.citation: Curr Opin Anaesthesiol. 2005 Dec;18(6):625-31
references.pmid: 16534303
references.citation: BMC Neurosci. 2010;11:122
references.pmid: 20863382
references.citation: Neuroscience. 2007 Oct 12;149(1):232-41
references.pmid: 17850979
references.citation: Int Anesthesiol Clin. 2008 Summer;46(3):55-73
references.pmid: 18617818
references.citation: Neuroimage. 2011 Mar 1;55(1):67-86
references.pmid: 21111827
references.citation: Brain Res. 2015 Feb 19;1598:31-45
references.pmid: 25498982
references.citation: Nat Neurosci. 2009 Jan;12(1):85-91
references.pmid: 19098905
references.citation: Hum Brain Mapp. 1999;8(4):194-208
references.pmid: 10619414
references.citation: Trends Pharmacol Sci. 2005 Oct;26(10):503-10
references.pmid: 16126282
references.citation: Neuroimage. 2003 Jun;19(2 Pt 1):402-11
references.pmid: 12814589
references.citation: Anesthesiology. 2010 Nov;113(5):1038-53
references.pmid: 20885292
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2681-6
references.pmid: 20133802
references.citation: Nature. 2003 Nov 27;426(6965):442-6
references.pmid: 14647382
references.citation: Hum Brain Mapp. 2012 Oct;33(10):2487-98
references.pmid: 21932265
references.citation: Anesthesiology. 2007 Dec;107(6):983-91
references.pmid: 18043067
references.citation: Anesthesiology. 2009 Aug;111(2):231-9
references.pmid: 19568167
references.citation: J Physiol. 1959 Oct;148:574-91
references.pmid: 14403679
references.citation: PLoS One. 2012;7(11):e49855
references.pmid: 23185462
references.citation: Nat Rev Neurosci. 2008 Feb;9(2):97-107
references.pmid: 18200026
references.citation: Neurosci Lett. 2006 Jul 24;402(3):216-21
references.pmid: 16678343
references.citation: Cereb Cortex. 2010 May;20(5):1020-36
references.pmid: 19737780
references.citation: J Neurophysiol. 2001 Aug;86(2):1062-6
references.pmid: 11495976
references.citation: Prog Brain Res. 2005;150:229-44
references.pmid: 16186027
references.citation: Neuroimage. 2011 Jul 1;57(1):198-205
references.pmid: 21524704
references.citation: Curr Opin Neurobiol. 2006 Aug;16(4):377-84
references.pmid: 16842989
references.citation: N Engl J Med. 2003 May 22;348(21):2110-24
references.pmid: 12761368
references.citation: Curr Opin Neurobiol. 2013 Apr;23(2):216-22
references.pmid: 23265963
references.citation: Nature. 2007 May 3;447(7140):83-6
references.pmid: 17476267
references.citation: Br J Anaesth. 2009 Jul;103(1):61-9
references.pmid: 19508978
references.citation: Neuron. 2005 Oct 20;48(2):315-27
references.pmid: 16242411
references.citation: Science. 2009 May 29;324(5931):1207-10
references.pmid: 19478185
references.citation: J Neurosci Methods. 2006 Sep 30;156(1-2):322-32
references.pmid: 16563517