Biology subjects

Soares, S.

Publications and source records attributed to Soares, S..

6 recordsLinked to original sources

bioRxiv2023

ArMo: An Articulated Mesh Approach for Mouse 3D Reconstruction

Characterizing animal behavior requires methods to distill 3D movements from video data. Though keypoint tracking has emerged as a widely used solution to this problem, it only provides a limited view of pose, reducing the body of an animal to a sparse set of experimenter-defined points. To more completely capture 3D pose, recent studies have fit 3D mesh models to subjects in image and video data. However, despite the importance of mice as a model organism in neuroscience research, these methods have not been applied to the 3D reconstruction of mouse behavior. Here, we present ArMo, an articulated mesh model of the laboratory mouse, and demonstrate its application to multi-camera recordings of head-fixed mice running on a spherical treadmill. Using an end-to-end gradient based optimization procedure, we fit the shape and pose of a dense 3D mouse model to data-derived keypoint and point cloud observations. The resulting reconstructions capture the shape of the animals surface while compactly summarizing its movements as a time series of 3D skeletal joint angles. ArMo therefore provides a novel alternative to the sparse representations of pose more commonly used in neuroscience research.

animal behavior and cognition↗

bioRxiv2021

Cognitive experience alters cortical involvement in navigation decisions

The neural correlates of decision-making have been investigated extensively, and recent work aims to identify under what conditions cortex is actually necessary for making accurate decisions. We discovered that mice with distinct cognitive experiences, beyond sensory and motor learning, use different cortical areas and neural activity patterns to solve the same task, revealing past learning as a critical determinant of whether cortex is necessary for decision-making. We used optogenetics and calcium imaging to study the necessity and neural activity of multiple cortical areas in mice with different training histories. Posterior parietal cortex and retrosplenial cortex were mostly dispensable for accurate decision-making in mice performing a simple navigation-based decision task. In contrast, these areas were essential for the same simple task when mice were previously trained on complex tasks with delay periods or association switches. Multi-area calcium imaging showed that, in mice with complex-task experience, single-neuron activity had higher selectivity and neuron-neuron correlations were weaker, leading to codes with higher task information. Therefore, past experience sets the landscape for how future tasks are solved by the brain and is a key factor in determining whether cortical areas have a causal role in decision-making.

neuroscience↗

bioRxiv2020

Inferring brain-wide interactions using data-constrained recurrent neural network models

Behavior arises from the coordinated activity of numerous anatomically and functionally distinct brain regions. Modern experimental tools allow unprecedented access to large neural populations spanning many interacting regions brain-wide. Yet, understanding such large-scale datasets necessitates both scalable computational models to extract meaningful features of inter-region communication and principled theories to interpret those features. Here, we introduce Current-Based Decomposition (CURBD), an approach for inferring brain-wide interactions using data-constrained recurrent neural network models that directly reproduce experimentally-obtained neural data. CURBD leverages the functional interactions inferred by such models to reveal directional currents between multiple brain regions. We first show that CURBD accurately isolates inter-region currents in simulated networks with known dynamics. We then apply CURBD to multi-region neural recordings obtained from mice during running, macaques during Pavlovian conditioning, and humans during memory retrieval to demonstrate the widespread applicability of CURBD to untangle brain-wide interactions underlying behavior from a variety of neural datasets.

neuroscience↗

bioRxiv2020

Dorsolateral striatal circuits support broadly opponent aspects of action suppression and production

Imbalance between action suppression and production characterizes several neurological disorders of the basal ganglia (BG)1. Relatedly, two major circuits of the BG, the direct and indirect pathways, are hypothesized to function in opposition, promoting and suppressing actions, respectively2. Yet activity of neurons initiating the two pathways, striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons, appears to be positively correlated around movement, apparently contradicting direct-indirect functional opponency3. Here we show that while coactivation occurs during movement, action suppression produces systematic features of functional opponency between the two pathways. First, suppression produced elevated iMSN activity and diminished dMSN activity in dorsolateral striatum of mice. Second, as the need to suppress movements to one or the other side of the body evolved over time, so too did the relative levels of activity in the two hemispheres, and in opposite patterns in the two pathways. Lastly, optogenetic inhibition of dMSNs, but not iMSNs, slowed movements without affecting their likelihood, whereas inhibition of iMSNs, but not dMSNs, disrupted whether and when mice suppressed or produced particular actions. These data demonstrate large-scale opponency in the activity of neurons that initiate the direct and indirect pathways of the BG, but suggest distinct action-related functions of each pathway. Specifically, the data support a novel model of sensorimotor striatum wherein the direct pathway appears to be necessary for augmenting generalized movement vigor, and the indirect pathway for the proactive suppression of specific behaviors.

neuroscience↗

bioRxiv2020

Dopamine responses reveal efficient coding of cognitive variables

Reward expectations based on internal knowledge of the external environment are a core component of adaptive behavior. However, internal knowledge may be inaccurate or incomplete due to errors in sensory measurements. Some features of the environment may also be encoded inaccurately to minimise representational costs associated with their processing. We investigate how reward expectations are affected by differences in internal representations by studying rodents behaviour and dopaminergic activity while they make time based decisions. Several possible representations allow a reinforcement learning agent to model animals choices during the task. However, only a small subset of highly compressed representations simultaneously reproduce, both, animals behaviour and dopaminergic activity. Strikingly, these representations predict an unusual distribution of response times that closely matches animals behaviour. These results can inform how constraints of representational efficiency may be expressed in encoding representations of dynamic cognitive variables used for reward based computations.

neuroscience↗

bioRxiv2020

Long term AAV2/9-mediated silencing of PMP22 prevents CMT1A disease in rats and validates skin biomarkers as treatment outcome measure

Charcot-Marie-Tooth disease 1A (CMT1A) results from a duplication of the PMP22 gene leading to an excess of PMP22, a deficit of myelination and an instability of the myelin sheath in peripheral nerves. Patients present with reduced nerve conduction velocity, muscle waste, hand and foot deformations and foot drop walking problems. As gene silencing therapy has been shown to be effective in other monogenic neurological disorders, we evaluated the safety and efficacy of recombinant adeno-associated viral vector serotype 9 (AAV2/9)-based gene therapy for CMT1A. AAV2/9-mediated delivery of eGFP and shRNAs targeting PMP22 mRNA in the sciatic nerve allowed widespread gene expression in myelinating Schwann cells in mouse, rat and nonhuman primate. The treatment restored wild-type PMP22 level, increased myelination and prevented motor and sensory impairment over 12 months in a rat model of CMT1A. Intra-nerve injection limited off-target transduction and immune response to barely detectable levels. A combination of previously characterized human skin biomarkers successfully discriminated treated animals from their untreated littermate controls indicating their potential use as part of outcome measures in future clinical trials. Our results support intra nerve injection of AAV2/9 as an effective strategy for the treatment of CMT1A as well as other demyelinating CMT diseases.

neuroscience↗