Biology subjects

Crair, M.

Publications and source records attributed to Crair, M..

6 recordsLinked to original sources

bioRxiv2023

IN SITU IMAGING OF RETINAL CALCIUM DYNAMICS IN AWAKE ANIMALS

Mammalian vision starts in the retina. The study of retinal circuits in vivo is essential for comprehending retinal neural dynamics under physiological conditions. While several transpupillary retina imaging techniques have been utilized in anesthetized animals, the in situ imaging of retinal activity in awake animals has been more difficult to accomplish. These limits have frustrated crucial scientific inquiries, such as how visual processing in the retina is modulated by behavior. In this study, we present novel experimental approaches that stabilize the eye to access in situ retinal dynamics with optical techniques in awake mice. Our findings demonstrate that this method can be utilized to: 1) image neural activity in distinct cell types across multiple ages, 2) record meso-scale (e.g. spontaneous retinal waves) or cellular retinal dynamics, 3) study retina functional connectivity in vivo, and 4) pharmacologically manipulate retinal activity. We applied these novel approaches to demonstrate that retinal activity is strongly modulated by movement through H1R-dependent histaminergic transmission in vivo, even at the amacrine cell level. These methods are suitable to simultaneously record retinal and brain activity dynamics or to investigate retinal responses to patterned visual stimuli, making accessible fundamental questions about visual processing that have previously been very challenging to achieve.

neuroscience↗

bioRxiv2022

Functional network organization of the mouse cortex determined by wide-field fluorescence imaging shares some --but not all-- properties revealed with simultaneous fMRI-BOLD

Work in humans and animals shows that the brain can be decomposed into large-scale functional networks. Whereas most studies, especially in humans, use the blood-oxygenation-level-dependent (BOLD) signal, the relationship between BOLD and neuronal activity is complex and incompletely understood. This limits our ability to interpret and apply measures derived from fMRI-BOLD. Here, we employ wide-field Ca2+ imaging simultaneously recorded with fMRI-BOLD in highly-sampled mice expressing GCaMP6f in excitatory neurons. These unique data enabled us to characterize the similarities and differences between networks discoverable by each modality. Importantly, we applied a network partitioning approach that uses a mixed-membership algorithm, which allows brain regions to participate in multiple networks with varying strengths. This contrasts with assuming regions belong to only one network. Our findings demonstrate that (1) most BOLD networks are detected via Ca2+ signals. (2) There is considerable overlapping--as opposed to disjoint--network organization that is evident from both modalities. (3) Large-scale networks determined by Ca2+ signals at low temporal frequencies (0.01 - 0.5 Hz)--as opposed to higher frequencies (0.5 - 5 Hz)--are more similar to those determined by BOLD. (4) Despite many similarities, differences emerge across modes including the spatial distribution of membership diversity (the extent to which regions affiliate with multiple networks). In sum, Ca2+ imaging of excitatory neurons confirms that the mouse cortex is functionally organized into overlapping large-scale networks in a manner that reflects many, but not all, properties observable with simultaneous fMRI-BOLD; affirming the neural origins of patterns of brain organization that are evident in a clinically accessible neuroimaging modality.

neuroscience↗

bioRxiv2022

A preprocessing and functional connectivity analysis pipeline for mesoscale calcium imaging

To improve bench-to-bedside translation, it is integral that knowledge flow bidirectionally--from animal models to humans, and vice versa. This requires common analytical frameworks, as well as open software and data sharing practices. We share a new pipeline (and test dataset) for the preprocessing of wide-field optical fluorescence imaging data--an emerging mode applicable in animal models--as well as results from a functional connectivity and graph theory analysis inspired by recent work in the human neuroimaging field. The approach is demonstrated using a dataset comprised of two test-cases: (1) data from animals imaged during awake and anesthetized conditions with excitatory neurons labeled, and (2) data from awake animals with different genetically encoded fluorescent labels that target either excitatory neurons or inhibitory interneuron subtypes. Both seed-based connectivity and graph theory measures (global efficiency, transitivity, modularity, and characteristic path-length) are shown to be useful in quantifying differences between wakefulness states and cell populations. Wakefulness state and cell type show widespread effects on canonical network connectivity with variable frequency band dependence. Differences between excitatory neurons and inhibitory interneurons are observed, with somatostatin expressing inhibitory interneurons emerging as notably dissimilar from parvalbumin and vasoactive polypeptide expressing cells. In sum, we demonstrate that our pipeline can be used to examine brain state and cell-type differences in mesoscale imaging data, aiding translational neuroscience efforts. In line with open science practices, we freely release the pipeline and data to encourage other efforts in the community.

neuroscience↗

bioRxiv2020

Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation before hearing onset. Effects of the evolving peripheral firing pattern on spontaneous activity in the central auditory system are not well understood. Here, we describe the wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the medial olivochlear (MOC) system. Knocking out the 9/10 nicotinic acetylcholine receptor, a requisite part of the efferent cholinergic pathway, abolishes these bilateral correlations. Pharmacological and chemogenetic experiments confirm that the MOC system is necessary and sufficient to produce the bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, our results demonstrate how ascending and descending pathways collectively shape spontaneous activity patterns in the auditory system and reveal the essential role of the MOC efferent system in linking otherwise independent streams of bilateral spontaneous activity during the prehearing period.

neuroscience↗

bioRxiv2018

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

Spontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.

neuroscience↗

bioRxiv2018

Synapse-selective control of cortical maturation and plasticity engages an interneuron-autonomous synaptic switch

HighlightsO_LIThe synaptogenic molecule SynCAM 1 is selectively regulated by visual experience\nC_LIO_LISynCAM 1 controls thalamic input onto cortical Parvalbumin (PV+) interneurons\nC_LIO_LIPV+-specific knockdown of SynCAM 1 arrests maturation of cortical inhibition\nC_LIO_LIThalamic excitation onto PV+ interneurons is essential for critical period closure\nC_LI\n\neTOC BlurbRibic et al. show that network plasticity in both young and adult cortex is restricted by the synapse organizing molecule SynCAM 1. On a cellular level, it functions in Parvalbumin-positive interneurons to recruit thalamocortical terminals. This controls the maturation of inhibitory drive and restricts plasticity in the cortex. These results reveal the synaptic locus of cortical plasticity and identify the first cell-autonomous synaptic factor for closure of cortical critical periods.\n\nSummaryBrain plasticity peaks early in life and tapers in adulthood. This is exemplified in the primary visual cortex, where brief loss of vision to one eye abrogates cortical responses to inputs from that eye during the critical period, but not in adulthood. The synaptic locus of critical period plasticity and the cell-autonomous synaptic factors timing these periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits visual cortex plasticity. SynCAM 1 selectively controls the number of excitatory thalamocortical (TC) inputs onto Parvalbumin (PV+) interneurons and loss of SynCAM 1 in turn impairs the maturation of TC-driven feed-forward inhibition. SynCAM 1 acts in cortical PV+ interneurons to perform these functions and its PV+-specific knockdown prevents the age-related plasticity decline. These results identify a synapse type-specific, cell-autonomous mechanism that governs circuit maturation and closes the visual critical period.

neuroscience↗