Ca2+ signaling in astrocytes is sleep-wake state specific and modulates sleep, bioRxiv, 2019-08-30
SummaryAstrocytic Ca2+ signaling has been intensively studied in health and disease but remains uncharacterized in sleep. Here, we employed a novel activity-based algorithm to assess astrocytic Ca2+ signals in the barrel cortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We discovered that Ca2+ signaling in astrocytes exhibits distinct features across the sleep-wake cycle and is reduced in sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow-wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Genetic ablation of a key astrocytic Ca2+ signaling pathway resulted in fragmentation of slow-wave sleep, yet increased the frequency of sleep spindles. Our findings suggest a role for astrocytic Ca2+ signaling in modulating sleep.
biorxiv neuroscience 100-200-users 2019A neural network model of flexible grasp movement generation, bioRxiv, 2019-08-25
AbstractOne of the main ways we interact with the world is using our hands. In macaques, the circuit formed by the anterior intraparietal area, the hand area of the ventral premotor cortex, and the primary motor cortex is necessary for transforming visual information into grasping movements. We hypothesized that a recurrent neural network mimicking the multi-area structure of the anatomical circuit and trained to transform visual features into the muscle fiber velocity required to grasp objects would recapitulate neural data in the macaque grasping circuit. While a number of network architectures produced the required kinematics, modular networks with visual input and activity that was encouraged to be biologically realistic best matched neural data and the inter-area differences present in the biological circuit. Network dynamics could be explained by simple rules that also allowed the correct prediction of kinematics and neural responses to novel objects, providing a potential mechanism for flexibly generating grasping movements.
biorxiv neuroscience 200-500-users 2019An easy-to-assemble, robust, and lightweight drive implant for chronic tetrode recordings in freely moving animals, bioRxiv, 2019-08-25
AbstractTetrode arrays are the gold-standard method for neuronal recordings in many studies with behaving animals, especially for deep structures and chronic recordings. Here we outline an improved drive design for use in freely behaving animals. Our design makes use of recently developed technologies to reduce the complexity and build time of the drive while maintaining a low weight. The design also presents an improvement over many existing designs in terms of robustness and ease of use. We describe two variants a 16 tetrode implant weighing ∼2 g for mice, bats, tree shrews and similar animals, and a 64 tetrode implant weighing ∼16 g for rats, and similar animals.These designs were co-developed and optimized alongside a new class of drive-mounted feature-rich amplifier boards with ultra-thin RF tethers, as described in an upcoming paper (Newman, Zhang et al., in prep). This design significantly improves the data yield of chronic electrophysiology experiments.
biorxiv neuroscience 0-100-users 2019Expression profiling of the mature C. elegans nervous system by single-cell RNA-Sequencing, bioRxiv, 2019-08-17
AbstractA single neuron and its synapses define the fundamental structural motif of the brain but the underlying gene expression programs that specify individual neuron types are poorly understood. To address this question in a model organism, we have produced a gene expression profile of >90% of the individual neuron classes in the C. elegans nervous system, an ensemble of neurons for which both the anatomy and connectivity are uniquely defined at single cell resolution. We generated single cell transcriptomes for 52,412 neurons that resolve as clusters corresponding to 109 of the canonical 118 neuron classes in the mature hermaphrodite nervous system. Detailed analysis revealed molecular signatures that further subdivide identified classes into specific neuronal subtypes. Notably, neuropeptide-related genes are often differentially expressed between subtypes of the given neuron class which points to distinct functional characteristics. All of these data are publicly available at our website (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpwww.cengen.org>httpwww.cengen.org<jatsext-link>) and can be interrogated at the web application SCeNGEA (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpscengen.shinyapps.ioSCeNGEA>httpscengen.shinyapps.ioSCeNGEA<jatsext-link>). We expect that this gene expression catalog will spur the goal of delineating the underlying mechanisms that define the developmental lineage, detailed anatomy, synaptic connectivity and function of each type of C. elegans neuron.
biorxiv neuroscience 100-200-users 2019Modulation of sensory behavior and food choice by an enteric bacteria-produced neurotransmitter, bioRxiv, 2019-08-15
AbstractAnimals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms including microbes1. Some bacteria produce bioactive neurotransmitters which have been proposed to modulate host nervous system activity and behaviors2. However, the mechanistic basis of this microbiota-brain modulation and its physiological relevance is largely unknown. Here we show that in C. elegans, the neuromodulator tyramine (TA) produced by gut-colonizing commensal Providencia bacteria can bypass the requirement for host TA biosynthesis to manipulate a host sensory decision. Bacterially-produced TA is likely converted to octopamine (OA) by the host tyramine beta-hydroxylase enzyme. OA, in turn, targets the OCTR-1 receptor on the ASHASI sensory neurons to modulate an aversive olfactory response. We identify genes required for TA biosynthesis in Providencia, and show that these genes are necessary for modulation of host behavior. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially-produced TA. Our results demonstrate that a neurotransmitter produced by gut microbiota mimics the functions of the cognate host molecule to override host control of a sensory decision, thereby promoting fitness of both host and microbe.
biorxiv neuroscience 0-100-users 2019Dopamine waves as a mechanism for spatiotemporal credit assignment, bioRxiv, 2019-08-13
AbstractSignificant evidence supports the view that dopamine shapes reward-learning by encoding prediction errors. However, it is unknown whether dopamine decision-signals are tailored to the functional specialization of target regions. Here, we report a novel set of wave-like spatiotemporal activity-patterns in dopamine axons across the dorsal striatum. These waves switch between different activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. These specific motifs are associated with distinct task contexts At reward delivery, dopamine signals rapidly resynchronize into propagating waves with opponent directions depending on instrumental task contingencies. Moreover, dopamine dynamics during reward pursuit signal the extent to which mice have instrumental control and interact with reward waves to predict future behavioral adjustments. Our results are consistent with a computational architecture in which striatal dopamine signals are sculpted by inference about instrumental controllability and provide evidence for a spatiotemporally “vectorized” role of dopamine in credit assignment.
biorxiv neuroscience 100-200-users 2019