Orlowska-Feuer, P. | bioRxiv Science

bioRxiv2020

Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons

There is no consensus on the best optogenetic tool for neuronal inhibition. Lamprey parapinopsin ( Lamplight) is a Gi/o-coupled bistable animal opsin that can be activated and deactivated by short and long wavelength light, respectively. Since native mechanisms of neuronal inhibition frequently employ Gi/o signalling, we asked here whether Lamplight could be used for optogenetic silencing. We show that short (405nm) and long (525nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, and that combining these wavelengths can be used to achieve intermediate levels of activity. We demonstrate that these properties can be applied to produce switchable and scalable neuronal hyperpolarisation, and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. We show that expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, and that 405 and 525nm stimuli can produce responses of opposite sign in output neurons of the retina. Lamplight-driven responses to both activating (405nm) and deactivating (525nm) light can occur within 500ms and be elicited by intensities at least 10x below threshold for available inhibitory optogenetic tools. We conclude that Lamplight can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and rapidly reversible.

neuroscience↗

bioRxiv2020

Infra-slow modulation of fast beta/gamma oscillations in the mouse visual system.

Infra-slow (<0.02 Hz) and fast beta/gamma (20 - 100 Hz) oscillations in neurophysiological activity have been widely found in the subcortical visual system. While it is well established that fast beta/gamma oscillations are involved in visual processing, the role (if any) of infra-slow oscillations is currently unknown. One possibility is that infra-slow oscillations exert influence by modulating the amplitude of fast oscillations, yet the extent to which these different oscillations arise independently and interact remains unknown. We addressed these questions by recording in vivo spontaneous activity from subcortical visual system of visually intact mice, and animals whose retinal network was disrupted by advanced rod/cone degeneration (rd/rd cl) or melanopsin loss (Opn4-/- We found many neurons expressing only one type of oscillation, and indeed fast oscillations were absent in rd/rd cl. Conversely, neurons co-expressing the two oscillations were also common, and were encountered more often than expected by chance in visually intact but not Opn4-/- mice. Finally, where they co-occurred we found that beta/gamma amplitude was modulated by the infra-slow rhythm. Our data thus reveal that: 1.) infra-slow and beta-gamma oscillations are separable phenomena; and 2.) that they actively co-occur in a subset of neurones in which the phase of infra-slow oscillations define beta-gamma oscillation amplitude. These findings suggest that infra-slow oscillations could influence vision by modulating beta-gamma oscillations, and raise the possibility that disruptions in these oscillatory behaviours contribute to vision dysfunction in retinal dystrophy. KEY POINTS SUMMARYO_LINeurophysiological activity in the subcortical visual system fluctuates in both infra-slow and fast oscillatory ranges, however the level of co-occurrence and potential functional interaction of these rhythms is unknown. C_LIO_LIAnalyzing dark-adapted spontaneous activity in the mouse subcortical visual system, we find that these two types of oscillation interact uniquely through a population of neurons expressing both rhythms. C_LIO_LIGenetic ablation of rod/cone signaling potentiates infra-slow and abolishes fast beta/gamma oscillations while genetic ablation of melanopsin substantially diminishes the interaction between these two rhythms. C_LIO_LIOur results indicate that in an intact visual system the phase of infra-slow modulates fast beta/gamma oscillations. C_LIO_LIThus one possible impact of infra-slow oscillations in vision is to guide visual processing by interacting with fast narrowband oscillations. C_LI

neuroscience↗