Biology subjects

Yizhar, O.

Publications and source records attributed to Yizhar, O..

3 recordsLinked to original sources

bioRxiv2018

Dynamics of social representation in the mouse prefrontal cortex

The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and impairments in this region have been linked with social dysfunction in psychiatric disorders. Yet little is known of how the PFC encodes social information and of how social representations may be altered in such disorders. Here, we show that neurons in the medial PFC (mPFC) of freely behaving mice preferentially respond to socially-relevant sensory cues. Population activity patterns in the mPFC differed considerably between social and nonsocial stimuli and underwent experience-dependent refinement. In Cntnap2 knockout mice, a genetic model of autism, both the categorization of sensory stimuli and the refinement of social representations were impaired. Noise levels in spontaneous population activity were higher in Cntnap2 mice, and correlated strongly with the degree to which social representations were disrupted. Our findings elucidate the encoding of social sensory cues in the mPFC, and provide an important link between altered prefrontal dynamics and autism-associated social dysfunction.

neuroscience↗

bioRxiv2017

High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

Optogenetic silencing allows time-resolved functional interrogation of defined neuronal populations. However, the limitations of inhibitory optogenetic tools impose stringent constraints on experimental paradigms. The high light power requirement of light-driven ion pumps and their effects on intracellular ion homeostasis pose unique challenges, particularly in experiments that demand inhibition of a widespread neuronal population in vivo. Guillardia theta anion-conducting channelrhodopsins (GtACRs) are promising in this regard, due to their high single-channel conductance and favorable photon-ion stoichiometry. However, GtACRs show poor membrane targeting in mammalian cells, and the activity of such channels can cause transient excitation in the axon due to an excitatory chloride reversal potential in this compartment. Here we address both problems by enhancing membrane targeting and subcellular compartmentalization of GtACRs. The resulting GtACR-based optogenetic tools show improved photocurrents, greatly reduced axonal excitation, high light sensitivity and rapid kinetics, allowing highly efficient inhibition of neuronal activity in the mammalian brain.

neuroscience↗

bioRxiv2017

Identification Of Cellular-Activity Dynamics Across Large Tissue Volumes In The Mammalian Brain

Tracking the coordinated activity of cellular events through volumes of intact tissue is a major challenge in biology that has inspired significant technological innovation. Yet scanless measurement of the high-speed activity of individual neurons across three dimensions in scattering mammalian tissue remains an open problem. Here we develop and validate a computational imaging approach (SWIFT) that integrates high-dimensional, structured statistics with light field microscopy to allow the synchronous acquisition of single-neuron resolution activity throughout intact tissue volumes as fast as a camera can capture images (currently up to 100 Hz at full camera resolution), attaining rates needed to keep pace with emerging fast calcium and voltage sensors. We demonstrate that this large field-of-view, single-snapshot volume acquisition method--which requires only a simple and inexpensive modification to a standard fluorescence microscope--enables scanless capture of coordinated activity patterns throughout mammalian neural volumes. Further, the volumetric nature of SWIFT also allows fast in vivo imaging, motion correction, and cell identification throughout curved subcortical structures like the dorsal hippocampus, where cellular-resolution dynamics spanning hippocampal subfields can be simultaneously observed during a virtual context learning task in a behaving animal. SWIFTs ability to rapidly and easily record from volumes of many cells across layers opens the door to widespread identification of dynamical motifs and timing dependencies among coordinated cell assemblies during adaptive, modulated, or maladaptive physiological processes in neural systems.

neuroscience↗