Biology subjects

Wehr, M.

Publications and source records attributed to Wehr, M..

6 recordsLinked to original sources

bioRxiv2024

Olfactory bulb tracks breathing rhythms and place in freely behaving mice

Vertebrates sniff to control the odor samples that enter their nose. These samples can not only help identify odorous objects, but also locations and events. However, there is no receptor for place or time. Therefore, to take full advantage of olfactory information, an animals brain must contextualize odor-driven activity with information about when, where, and how they sniffed. To better understand contextual information in the olfactory system, we captured the breathing and movements of mice while recording from their olfactory bulb. In stimulus- and task-free experiments, mice structure their breathing into persistent rhythmic states which are synchronous with statelike structure in ongoing neuronal population activity. These population states reflect a strong dependence of individual neuron activity on variation in sniff frequency, which we display using "sniff fields" and quantify using generalized linear models. In addition, many olfactory bulb neurons have "place fields" that display significant dependence of firing on allocentric location, which were comparable with hippocampal neurons recorded under the same conditions. At the population level, a mouses location can be decoded from olfactory bulb with similar accuracy to hippocampus. Olfactory bulb place sensitivity cannot be explained by breathing rhythms or scent marks. Taken together, we show that the mouse olfactory bulb tracks breathing rhythms and self-location, which may help unite internal models of self and environment with olfactory information as soon as that information enters the brain.

neuroscience↗

bioRxiv2024

Cortex-wide spatiotemporal motifs of theta oscillations are coupled to freely moving behavior

Multisensory information is combined across the cortex and assimilated into the continuous production of ongoing behavior. In the hippocampus, theta oscillations (4-12 Hz) radiate as large-scale traveling waves, and serve as a scaffold for neuronal ensembles of multisensory information involved in memory and movement-related processing. An extension of such an encoding framework across the neocortex could similarly serve to bind disparate multisensory signals into ongoing, coherent, phase-coded processes. Whether the neocortex exhibits unique large-scale traveling waves distinct from that of the hippocampus however, remains unknown. Here, using cortex-wide electrocorticography in freely moving mice, we find that theta oscillations are organized into bilaterally-symmetric spatiotemporal "modes" that span virtually the entire neocortex. The dominant mode (Mode 1) is a divergent traveling wave that originates from retrosplenial cortex and whose amplitude correlates with mouse speed. Secondary modes are asynchronous spiral waves centered over primary somatosensory cortex (Modes 2 & 3), which become prominent during rapid drops in amplitude and synchrony (null spikes) and which underlie a phase reset of Mode 1. These structured cortex-wide traveling waves may provide a scaffold for large-scale phase-coding that allows the binding of multisensory information across all the regions of the cortex. Bulleted list of key resultsO_LICortical theta oscillations are organized into bilaterally-symmetric spatiotemporal modes that span the neocortex. C_LIO_LIThe dominant mode appears as a divergent traveling wave that originates in retrosplenial cortex and is correlated with mouse speed. C_LIO_LISecondary modes are asynchronous spiral waves centered over somatosensory cortex. C_LIO_LISecondary modes become prominent during transient drops in synchrony that underlie a phase reset of the dominant mode. C_LIO_LIWe hypothesize that spiral waves may provide a mechanism to exert large-scale phase separability, and assimilate information into ongoing multisensory processing across the neocortex. C_LI

neuroscience↗

bioRxiv2024

Modulation of metastable ensemble dynamics explains optimal coding at moderate arousal in auditory cortex

Past work has reported inverted-U relationships between arousal and auditory task performance, but the underlying neural network mechanisms remain unclear. To make progress, we recorded auditory cortex activity from behaving mice during passive tone presentation and simultaneously monitored pupil-indexed arousal. In these experiments, neural discriminability of tones was maximized at intermediate arousal, revealing a neural correlate of the inverted-U. We explained this arousal-dependent sound processing using a spiking model with clusters. In the model, stimulus discriminability peaked as the network transitioned from a multi-attractor phase exhibiting slow switching between metastable cluster activations (low arousal) to a single-attractor phase with uniform activity (high arousal). This transition also qualitatively captured arousal-induced reductions of neural variability observed in the data. Altogether, this study elucidates computational principles to explain interactions between arousal, neural discriminability, and variability, and suggests that transitions in the dynamical regime of cortical networks could underlie nonlinear modulations of sensory processing.

neuroscience↗

bioRxiv2024

Polygenic risk for schizophrenia converges on alternative polyadenylation as molecular mechanism underlying synaptic impairment

Schizophrenia (SCZ) is a genetically heterogenous psychiatric disorder of highly polygenic nature. Correlative evidence from genetic studies indicate that the aggregated effects of distinct genetic risk factor combinations found in each patient converge onto common molecular mechanisms. To prove this on a functional level, we employed a reductionistic cellular model system for polygenic risk by differentiating induced pluripotent stem cells (iPSCs) from 104 individuals with high polygenic risk load and controls into cortical glutamatergic neurons (iNs). Multi-omics profiling identified widespread differences in alternative polyadenylation (APA) in the 3 untranslated region of many synaptic transcripts between iNs from SCZ patients and healthy donors. On the cellular level, 3APA was associated with a reduction in synaptic density of iNs. Importantly, differential APA was largely conserved between postmortem human prefrontal cortex from SCZ patients and healthy donors, and strongly enriched for transcripts related to synapse biology. 3APA was highly correlated with SCZ polygenic risk and affected genes were significantly enriched for SCZ associated common genetic variation. Integrative functional genomic analysis identified the RNA binding protein and SCZ GWAS risk gene PTBP2 as a critical trans-acting factor mediating 3APA of synaptic genes in SCZ subjects. Functional characterization of PTBP2 in iNs confirmed its key role in 3APA of synaptic transcripts and regulation of synapse density. Jointly, our findings show that the aggregated effects of polygenic risk converge on 3APA as one common molecular mechanism that underlies synaptic impairments in SCZ.

neuroscience↗

bioRxiv2020

A head-mounted multi-camera system for electrophysiology and behavior in freely-moving mice

Advances in the ability to monitor freely-moving mice may prove valuable for the study of behavior and its neural correlates. Here we describe a head-mounted multi-camera system for mice, comprised of inexpensive miniature analog camera modules. We illustrate the use of this system with several natural behaviors including prey capture, courtship, jumping, and exploration. With a four-camera headset, monitoring the eyes, ears, whiskers, rhinarium, and binocular visual field can all be achieved simultaneously with high-density electrophysiology. With appropriate focus and positioning, all eye movements can be captured, including cyclotorsion. For studies of vision and eye movements, cyclotorsion provides the final degree of freedom required to reconstruct the visual scene in retinotopic coordinates or to investigate the vestibulo-ocular reflex in mice. Altogether, this system allows for comprehensive measurement of freely-moving mouse behavior, enabling a more holistic and multimodal approach to investigate ethological behaviors and other processes of active perception.

neuroscience↗

bioRxiv2019

Autopilot: Automating behavioral experiments with lots of Raspberry Pis.

Neuroscience needs behavior, and behavioral experiments require the coordination of large numbers of heterogeneous hardware components and data streams. Currently available tools strongly limit the complexity and reproducibility of experiments. Here we introduce Autopilot, a complete, open-source Python framework for experimental automation that distributes experiments over networked swarms of Raspberry Pis. Autopilot enables qualitatively greater experimental flexibility by allowing arbitrary numbers of hardware components to be combined in arbitrary experimental designs. Research is made reproducible by documenting all data and task design parameters in a human-readable and publishable format at the time of collection. Autopilot provides a high-level set of programming tools while maintaining submillisecond performance at a fraction of the cost of traditional tools. Taking seriously the social nature of code, we scaffold shared knowledge and practice with a publicly editable semantic wiki and a permissive plugin system. Autopilots flexible, scalable architecture allows neuroscientists to work together to design the next generation of experiments to investigate the behaving brain.

animal behavior and cognition↗