Gamma-Band Resonance Of Visual Cortex To Optogenetic Stimulation

Abstract

Activated visual cortex typically engages in neuronal synchronization in the gamma-frequency band (30-90 Hz). Gamma-band synchronization is related to cognitive functioning, and its mechanisms have been extensively investigated, predominantly through in-vitro studies. To further elucidate its mechanisms in-vivo, we performed simultaneous optogenetic stimulation and electrophysiological recordings of visual cortical areas 17 and 21a in the anesthetized cat. Viral transfection with AAV1 or AAV9 under a CamKII promoter led to robust Channelrhodopsin-2 (ChR2) expression. Immunohistochemical analysis showed that all ChR2-expressing neurons were negative for Parvalbumin, consistent with predominant or exclusive expression in excitatory neurons. Optogenetic stimulation used primarily surface illumination directly above the transfected and recorded cells. Stimulation with constant light led to strong and sustained gamma-band synchronization with strength and bandwidth similar to visually induced gamma. Rhythmic stimulation with light-pulse trains or sinusoidal light modulation revealed strongest resonance for gamma-band frequencies. Gamma resonance was confirmed by optogenetic white-noise stimulation. White-noise stimulation allowed the quantification of the transfer function between the optogenetic stimulation and the local field potential response. This transfer function showed a dominant peak in the gamma band. Thus, we find that visual cortical circuits resonate most strongly to gamma-band components in their input. This resonance renders both the sensitivity to input, and the output of these circuits, selectively tuned to gamma.\n\nSignificance StatementActivated groups of cortical neurons often display rhythmic synchronization in the gamma-frequency band (30-90 Hz). Gamma-band synchronization is particularly well studied in visual cortex. We used optogenetics to control visual cortex neurons with light. Different optogenetic stimulation protocols, using constant light, rhythmically modulated light or white-noise modulated light, all demonstrated that the investigated circuits predominantly resonate to stimulation in the gamma band. The observed gamma-band resonance renders visual cortical circuits most sensitive to gamma-rhythmic synaptic inputs. This in turn renders their spike output and the ensuing interareal synchronization gamma rhythmic.\n\nThis work was supported by DFG (SPP 1665, FOR 1847, FR2557/5-1-CORNET to P.F.; EXC 1086, DI 1908/5-1, DI 1908/6-1 to I.D.), BMBF (01GQ1301 to I.D.), EU (HEALTH-F2-2008-200728-BrainSynch, FP7-604102-HBP, FP7-600730-Magnetrodes to P.F.; ERC Starting Grant OptoMotorPath to I.D.), a European Young Investigator Award to P.F., the FENS-Kavli Network of Excellence to I.D., National Institutes of Health (1U54MH091657-WU-Minn-Consortium-HCP to P.F.), the LOEWE program (NeFF to P.F. and I.D.). Present address of I.D.: Optophysiology, Bernstein Center and BrainLinks-BrainTools, University of Freiburg, Albertstrase 23, 79104 Freiburg, Germany.\n\nAuthor contributionsJ.N, C.M.L., T.W., P.F. designed research; J.N, C.M.L., T.W., P.J., I.D., P.F. performed experiments; J.N., C.M.L., T.W. analyzed data; J.N., P.F. wrote the paper.