Biology subjects

Frank, T.

Publications and source records attributed to Frank, T..

5 recordsLinked to original sources

bioRxiv2026

Distributed representations of chemosensory valence in a naive vertebrate brain

Chemical cues guide essential behaviors by signaling food, danger, and social information. A major dimension of chemosensory processing is valence, which biases animals toward approach or avoidance, yet its brain-wide organization in vertebrates remains unclear. Here, we used larval zebrafish to map neuronal activity associated with behaviorally defined appetitive and aversive chemosensory cues. Free-swimming assays identified a chemically diverse stimulus panel that elicited robust approach or avoidance, and key valence-dependent motor signatures were preserved during partially immobilized two-photon Ca{superscript 2} imaging with simultaneous tail tracking. Brain-wide activity revealed partly distinct patterns of stimulus identity, valence-related activity, and movement-correlated neuronal recruitment. Stimulus identity was strongest in the olfactory bulb and pallium, whereas small, coordinated valence-related populations were distributed across multiple telencephalic and diencephalic regions. These populations were partly separable from movement-correlated neurons, especially in forebrain regions, but showed valence-specific, opposing relationships with motor output. Together, our findings show that chemosensory valence-related activity in a naive vertebrate brain is not confined to a single sensory or motor-associated region, but is organized across a distributed, regionally structured brain-wide architecture. HIGHLIGHTSNaive larval zebrafish show appetitive and aversive chemosensory behaviors that are preserved during imaging Chemosensory stimuli evoke widespread brain activity, revealing distributed stimulus identity and valence representations Valence-encoding neurons form small, coordinated populations across multiple forebrain regions Valence-related activity is partly separable from movement-correlated activity

neuroscience↗

bioRxiv2024

Computational functions of precisely balanced neuronal assemblies in an olfactory memory network

Structured connectivity in the brain organizes information by constraining neuronal dynamics. Theoretical models predict that memories are represented by balanced assemblies of excitatory and inhibitory neurons, but the existence and functions of such EI assemblies are difficult to explore. We addressed these issues in telencephalic area Dp of adult zebrafish, the homolog of piriform cortex, using computational modeling, population activity measurements, and optogenetic perturbations. Modeling revealed that precise balance of EI assemblies is important to prevent not only excessive firing rates ("runaway activity") but also the stochastic occurrence of high pattern correlations ("runaway correlations"). Consistent with model-derived predictions, runaway correlations emerged in Dp when synaptic balance was perturbed by optogenetic manipulations of fast-spiking feedback interneurons. Moreover, runaway correlations were driven by sparse subsets of strongly active neurons, rather than by a general broadening of tuning curves. These results reveal novel computational functions of EI assemblies in an autoassociative olfactory memory network and support the hypothesis that EI assemblies organize information on continuous representational manifolds rather than discrete attractor landscapes.

neuroscience↗

bioRxiv2023

The COMBO window: A chronic cranial implant for multiscale circuit interrogation in mice

Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures, and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant - the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window. The COMBO window enables chronic imaging of large portions of the brain in head-fixed mice while preserving orofacial movements. We validate the COMBO window stability using both brain-wide fUS and multi-site two-photon imaging. Moreover, we demonstrate how the COMBO window facilitates the combination of optogenetics, fUS and electrophysiology in the same animals to study the effects of circuit perturbations at both the brain-wide and single-neuron level. Overall, the COMBO window provides a versatile solution for performing multimodal brain recordings in head-fixed mice.

neuroscience↗

bioRxiv2021

Spatiotemporal NF-κB dynamics encodes the position, amplitude and duration of local immune inputs

Infected cells communicate through secreted signaling molecules like cytokines, which inform nearby cells about the type, severity and location of pathogens. How differences in cytokine secretion affect inflammatory signaling over space and time, and how responding cells decode information from propagating cytokine signals are not understood. By computationally and experimentally studying NF-{kappa}B dynamics in co-cultures of signal sending cells (macrophages) and receiving cells (fibroblasts), we found that cytokine signals are transmitted by wave-like propagation of NF-{kappa}B activity and create well-defined cellular activation zones in a responding cell population. Remarkably, NF-{kappa}B dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially-resolved transcriptional analysis revealed that responding cells transmit local cytokine information to distance specific pro-inflammatory gene expression patterns, creating "gene expression zones" in the population. Despite single-cell variability, the size and duration of the signaling zone is tightly controlled by the macrophage cytokine secretion profile. Our results highlight how macrophages tune their cytokine secretion dynamics to control signal transmission distance, and how NF-{kappa}B interprets these signals to coordinate inflammatory response in space and time.

systems biology↗

bioRxiv2020

Identification of a novel population of peripheral sensory neuron that regulates blood pressure

The vasculature is innervated by a network of peripheral afferents that sense and regulate blood flow. Here, we describe a system of non-peptidergic sensory neurons with cell bodies in the spinal ganglia that regulate vascular tone in the distal arteries. We identify a population of mechanosensitive neurons marked by TrkC and Tyrosine hydroxylase in the dorsal root ganglia that project to blood vessels. Local stimulation of these neurons decreases vessel diameter and blood flow, while systemic activation increases systolic blood pressure and heart rate variability via the sympathetic nervous system. Chemogenetic inactivation or ablation of the neurons provokes variability in local blood flow leading to a reduction in systolic blood pressure, increased heart rate variability and ultimately lethality within 48 hours. Thus, TrkC/Tyrosine hydroxylase positive sensory neurons form part of a sensory feedback mechanism that maintains cardiovascular homeostasis through the autonomic nervous system.

neuroscience↗