Biology subjects

Dunn, T. W.

Publications and source records attributed to Dunn, T. W..

9 recordsLinked to original sources

bioRxiv2025

VQ-MAP: a flexible, versatile framework for animal behavior understanding

The brain generates behaviors that reflect configurations and computations of neural systems. Animal pose analysis can comprehensively profile behaviors in terms of stereotyped action expression, but the absence of common tracking standards makes it difficult to relate measurements across labs and experiments, hindering data exchange and collective knowledge building. Here, we present VQ-MAP, a versatile approach capable of mapping 2D or 3D keypoint sequences with divergent pose formats into a common set of discrete behavioral motifs. VQ-MAP utilizes permutation-invariant attention blocks for keypoint-agnostic processing and a quantized latent space for fast, interpretable delineation of motifs organized into type-subtype hierarchies. We deployed VQ-MAP to align and harmonize heterogeneous pose datasets, co-profiling rodent behaviors in multiple species and models of autism. In longitudinal recordings of rat behavioral maturation, VQ-MAP revealed developmental trajectories connecting specific behaviors across periods of substantial bodily growth and change. By unifying heterogeneous behavioral measurements, our framework will accelerate neurobiological discovery and help the community exercise the full potential of large-scale behavioral datasets.

neuroscience↗

bioRxiv2025

Cortex-Wide Substrates for Body Schema and Action Awareness

The concept of the body schema originated from studies of patients with cortical lesions who were unable to localize their body parts in space or perceive passive movements (Head & Holmes, 1911). Current consensus defines the body schema as the brains internal representation of the body configuration in space used for both embodied perception and voluntary action (de Vignemont, 2010; Berlucchi & Aglioti, 2010; Vallar et al., 2025). Despite extensive research, how the cortex efficiently encodes the vast repertoire of body postures to support natural behavior remains poorly understood. Here, we reveal the representational format underlying the body schema by combining large-scale electrophysiological recordings with full-body 3D tracking and joint angle computation in freely behaving mice. Across cortical regions, neurons encoded diverse postural features in distinct reference frames: posterior parietal cortex (PPC) populations preferentially encoded body midline-referenced features, while sensorimotor cortices utilized a gravity-referenced frame. Strikingly, during performance of different stereotyped actions, distinct cortical ensembles were selectively activated. These action ensembles fired in phase-locked sequences that tiled the full action cycle, providing a neural substrate for action awareness. A network model recapitulated these dynamics and identified low-dimensional action subspaces within population activity. Together, these findings reveal that the cortex organizes the body schema around actions, compressing high-dimensional kinematics into an efficient, body-midline-and gravity-anchored, action-aware neural code.

neuroscience↗

bioRxiv2025

Clustered VEGF Nanoparticles in Microporous Annealed Particle (MAP) Hydrogel Accelerates Functional Recovery and Brain Tissue Repair after Stroke

Ischemic stroke, a blockage in the vasculature of the brain that results in insufficient blood flow, is one of the worlds leading causes of disability. The cascade of inflammation and cell death that occurs immediately following stroke drives vascular and functional loss that does not fully recover over time, and no FDA-approved therapies exist that stimulate regeneration post-stroke. We have previously developed a hydrogel scaffold that delivered heparin nanoparticles with and without VEGF bound to their surface to promote angiogenesis and reduce inflammation, respectively. However, the inclusion of the naked heparin nanoparticles warranted concern over the development of bleeding complications. Here, we explore how microporous annealed particle (MAP) scaffolds functionalized with VEGF coated heparin nanoparticles can both reduce inflammation and promote angiogenesis - without the inclusion of free heparin nanoparticles. We show that our updated design not only successfully promotes de novo tissue formation, including the development of mature vessels and neurite sprouting, but it also leads to functional improvement in a photothrombotic stroke model. In addition, we find increased astrocyte infiltration into the infarct site correlated with mature vessel formation. This work demonstrates how our biomaterial design can enhance endogenous regeneration post-stroke while eliminating the need for excess heparin.

bioengineering↗

bioRxiv2024

Mapping the landscape of social behavior

Social interaction is integral to animal behavior. However, we lack tools to describe it with quantitative rigor, limiting our understanding of its principles and neuropsychiatric disorders, like autism, that perturb it. Here, we present a technique for high-resolution 3D tracking of postural dynamics and social touch in freely interacting animals, solving the challenging subject occlusion and part assignment problems using 3D geometric reasoning, graph neural networks, and semi-supervised learning. We collected over 140 million 3D postures in interacting rodents, featuring new monogenic autism rat lines lacking reports of social behavioral phenotypes. Using a novel multi-scale embedding approach, we identified a rich landscape of stereotyped actions, interactions, synchrony, and body contact. This enhanced phenotyping revealed a spectrum of changes in autism models and in response to amphetamine that were inaccessible to conventional measurements. Our framework and large library of interactions will greatly facilitate studies of social behaviors and their neurobiological underpinnings.

animal behavior and cognition↗

bioRxiv2021

The PAIR-R24M Dataset for Multi-animal 3D Pose Estimation

Understanding the biological basis of social and collective behaviors in animals is a key goal of the life sciences, and may yield important insights for engineering intelligent multi-agent systems. A critical step in interrogating the mechanisms underlying social behaviors is a precise readout of the 3D pose of interacting animals. While approaches for multi-animal pose estimation are beginning to emerge, they remain challenging to compare due to the lack of standardized training and benchmark datasets. Here we introduce the PAIR-R24M (Paired Acquisition of Interacting oRganisms - Rat) dataset for multi-animal 3D pose estimation, which contains 24.3 million frames of RGB video and 3D ground-truth motion capture of dyadic interactions in laboratory rats. PAIR-R24M contains data from 18 distinct pairs of rats and 24 different viewpoints. We annotated the data with 11 behavioral labels and 3 interaction categories to facilitate benchmarking in rare but challenging behaviors. To establish a baseline for markerless multi-animal 3D pose estimation, we developed a multi-animal extension of DANNCE, a recently published network for 3D pose estimation in freely behaving laboratory animals. As the first large multi-animal 3D pose estimation dataset, PAIR-R24M will help advance 3D animal tracking approaches and aid in elucidating the neural basis of social behaviors.

animal behavior and cognition↗

bioRxiv2021

Gigapixel behavioral and neural activity imaging with a novel multi-camera array microscope

The dynamics of living organisms are organized across many spatial scales. However, current cost-effective imaging systems can measure only a subset of these scales at once. We have created a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution recording from multiple spatial scales simultaneously, ranging from cellular structures to large-group behavioral dynamics. By collecting data from up to 96 cameras, we computationally generate gigapixel-scale images and movies with a field of view over hundreds of square centimeters at 5um sensitivity. This allows us to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales, including larval zebrafish, fruit flies, nematodes, carpenter ants, and slime mold. The MCAM architecture allows stereoscopic tracking of the z-position of organisms using the overlapping field of view from adjacent cameras. Further, we demonstrate the ability to acquire dual color fluorescence video of multiple freely moving zebrafish, recording neural activity via ratiometric calcium imaging. Overall, the MCAM provides a powerful platform for investigating cellular and behavioral processes across a wide range of spatial scales by removing the bottlenecks imposed by single-camera image acquisition systems.

bioengineering↗

bioRxiv2021

Excitatory postsynaptic calcium transients at Aplysia sensory-motor neuron synapses allow for quantal examination of synaptic strength over multiple days in culture

The ability to monitor changes in strength at individual synaptic contacts is required to test the hypothesis that specialized synapses maintain changes in synaptic strength that underlie memory. Measuring excitatory post-synaptic calcium transients through calcium permeable AMPA receptors is one way to monitor synaptic strength at individual synaptic contacts. Using a membrane targeted genetic calcium sensor, we demonstrate that one can measure synaptic events at individual synaptic contacts in Aplysia sensory-motor neuron synapses. These results show that synaptic strength is not evenly distributed between all contacts in these cultures, but dominated by multiquantal sites of synaptic contact. The probability, quantal size and quantal content can be measured over days at individual synaptic contacts using this technique. Surprisingly, most synaptic contacts were not found opposite presynaptic varicosities, but instead at areas of pre- and post-synaptic contact with no visible thickening of membranes. This technique shows promise in being able to address whether specialized synapses maintain synaptic strength underlying memory.

neuroscience↗

bioRxiv2019

Correcting for physical distortions in visual stimuli improves reproducibility in zebrafish neuroscience.

Breakthrough technologies for monitoring and manipulating single-neuron activity provide unprecedented opportunities for whole-brain neuroscience in larval zebrafish1-9. Understanding the neural mechanisms of visually guided behavior also requires precise stimulus control, but little prior research has accounted for physical distortions that result from refraction and reflection at an air-water interface that usually separates the projected stimulus from the fish10-12. Here we provide a computational tool that transforms between projected and received stimuli in order to detect and control these distortions. The tool considers the most commonly encountered interface geometry, and we show that this and other common configurations produce stereotyped distortions. By correcting these distortions, we reduced discrepancies in the literature concerning stimuli that evoke escape behavior13,14, and we expect this tool will help reconcile other confusing aspects of the literature. This tool also aids experimental design, and we illustrate the dangers that uncorrected stimuli pose to receptive field mapping experiments.

neuroscience↗

bioRxiv2019

Isoform specificity of PKMs during long-term facilitation in Aplysia is mediated through stabilization by KIBRA

Persistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems including the hermaphrodite marine mollusk, Aplysia californica. Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform was required, the kidney and brain expressed adaptor protein (KIBRA) was also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant negative (DN)-PKMs to erase LTF is correlated with isoform specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an alpha-helix handle in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in Aplysia.\n\nSignificance StatementLong lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs in not isoform specific, isoform specificity is defined by a handle helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.

neuroscience↗