Biology subjects

Whitlock, J. R.

Publications and source records attributed to Whitlock, J. R..

9 recordsLinked to original sources

bioRxiv2026

Active pursuit gates egocentric coding in Retrosplenial Cortex

Spatial navigation is commonly studied in static environments, but adaptive behavior frequently hinges on tracking moving goals in real time. Active pursuit exemplifies this challenge: it is an inherently egocentric spatial behavior requiring continuous localization of a moving target, yet the neural coding schemes supporting it remain poorly understood. We therefore performed Neuropixels recordings in the retrosplenial cortex (RSC), a hub for egocentric-to-allocentric reference frame transformations, during naturalistic bait-chasing. We identified head-centered target-encoding neurons that were functionally distinct from cells encoding environmental boundaries or static objects. Whereas egocentric boundary encoding was task-invariant, target-coding cells were specific to chasing and exhibited task-dependent retuning, characterized by enhanced ego-centric representation and reduced allocentric head-direction signaling during pursuit. Together, these findings demonstrate that classical egocentric and allocentric codes coexist with novel target tuning in the RSC, where target-coding neurons dynamically reweight their reference frames according to behavioral demands during pursuit.

neuroscience↗

bioRxiv2024

Prefrontal cortex encodes behavior states decoupled from movement

Prefrontal cortex is often viewed as an extension of the motor system, but little is understood of how it relates to natural motor behavior. We therefore tracked the kinematics of freely moving rats performing minimally structured tasks and measured which aspects of behavior were read out in prefrontal neural populations. Naturalistic behaviors such as rearing or chasing a bait were each encoded by unique neural ensembles, but the behavioral representations were not anchored to posture or movement. Rather, the coding of kinematic features depended on their relevance to the animals current behavior or which task the animal performed. Behavior-specific ensembles often preceded and outlasted physical actions and, accordingly, prefrontal population activity evolved at slower timescales than in motor cortex. These findings argue that prefrontal coding of behavior is not locked to motor output, and may instead reflect motivations to perform certain actions rather than the actions themselves. HighlightsO_LIPrefrontal neural ensembles uniquely encode different naturalistic actions C_LIO_LIBehavioral tuning is not explained by movement kinematics C_LIO_LIPopulation activity in prefrontal cortex evolves slower than in M1 C_LIO_LISingle-cell coding of behavior varies across tasks yet ensemble coding is stable C_LI

neuroscience↗

bioRxiv2023

A novel paradigm for operant social learning in rats

The ability to learn by observing the behavior of others is both energy efficient and brings high survival value, making it an important learning tool for many species in the animal kingdom. As such, several forms of observational learning have been documented in a myriad of species. In the laboratory, rodents have proven useful models for studying different forms of observational learning, however, the most robust learning paradigms typically rely on aversive stimuli, like foot shocks, to drive the social acquisition of fear. Non-fear-based tasks have also been developed, but these rarely succeed in having observer animals perform a new behavior de novo. Consequently, much less is known regarding the cellular mechanisms supporting non-fear-based types of learning, such as visuomotor skill acquisition. To address this we developed a reward-based social learning paradigm in adult rats, in which observer animals learn to tap lit spheres in a specific sequence by watching skilled demonstrators, with successful trials leading to rewarding intracranial stimulation in both observers and performers. Following three days of observation and a 24-hour delay, observer animals outperformed control animals on several metrics of task performance and efficiency, with a subset of observers demonstrating correct performance immediately when tested. This paradigm thus introduces a novel tool to investigate the neural circuits supporting observational learning and memory for visuomotor behavior, a phenomenon about which little is understood, particularly in rodents.

animal behavior and cognition↗

bioRxiv2022

Visuomotor interactions in the mouse forebrain mediated by extrastriate cortico-cortical pathways

The mammalian visual system can be broadly divided into two functional processing pathways: a dorsal stream supporting visually and spatially guided actions, and a ventral stream enabling object recognition. In rodents, the majority of visual signaling in the dorsal stream is transmitted to frontal motor cortices via extrastriate visual areas surrounding V1, but exactly where and to what extent V1 feeds into motor-projecting visual regions is not well known. To address this we employed a dual labeling strategy in male and female mice in which efferent projections from V1 were labeled anterogradely, and motor-projecting neurons in higher visual areas were labeled with retrogradely traveling adeno-associated virus (rAAV-retro) injected in M2. In flattened sections of dorsal cortex, the most pronounced colocalization V1 output and M2 input occurred in extrastriate areas AM, PM, RL and AL. Coronal sections further showed that neurons in both superficial and deep layers in these regions project to M2, but high resolution volumetric reconstructions revealed that the vast majority of putative synaptic contacts from V1 onto M2-projecting neurons occurred in layer 2/3. These findings support the existence of a dorsal processing stream in the mouse visual system, where visual signals reach motor cortex largely via feedforward projections in anteriorly and medially located extrastriate areas. Significance StatementVisually guided motor behavior depends on the long-distance relay of signals from visual cortex to frontal motor cortices, but the neuroanatomical connections linking visual and motor systems in rodents are not fully charted. Here, we characterized such pathways by injecting anterograde tracers in primary visual cortex (V1) and retrogradely traveling virus in motor cortex (M2), and visualizing where the projections overlapped. We found preferential colocalization of V1 output and M2-projecting neurons in anteriorly- and medially-located higher visual areas. 3D volumetric reconstructions further showed high rates of putative synaptic connections mainly in superficial layers. Thus, visual signals in the mouse dorsal visual stream reach motor areas at least in part via superficial, feedforward connections in a subset of extrastriate areas.

neuroscience↗

bioRxiv2022

Behavioral decomposition reveals rich encoding structure employed across neocortex

AO_SCPLOWBSTRACTC_SCPLOWThe Cortical population code is pervaded by activity patterns evoked by movement, but how such signals relate to the natural actions of unrestrained animals remains largely unknown, particularly in sensory areas. To address this we compared high-density neural recordings across four cortical regions (visual, auditory, somatosensory, motor) in relation to sensory modulation, posture, movement, and ethograms of freely foraging rats. Momentary actions, such as rearing or turning, were represented ubiquitously and could be decoded from all sampled structures. However, more elementary and continuous features, such as pose and movement, followed region-specific organization, with neurons in visual and auditory cortices preferentially encoding mutually distinct head-orienting features in world-referenced coordinates, and somatosensory and motor cortices principally encoding the trunk and head in egocentric coordinates. The tuning properties of synaptically coupled cells also exhibited connection patterns suggestive of different uses of behavioral information within and between regions. Together, our results speak for detailed, multi-level encoding of animal behavior subserving its dynamic employment in local cortical computations.

neuroscience↗

bioRxiv2021

TRACER: A toolkit to register and visualize anatomical coordinates in the rat brain

Recording technologies for rodents have seen huge advances in the last decade, allowing users to sample thousands of neurons simultaneously from multiple brain regions. This has prompted the need for digital tool kits to aid in curating anatomical data, however, existing tools either provide limited functionality or require users to be proficient in coding to use them. To address this we created HERBS, a comprehensive new tool for rodent users that offers a broad range of functionalities through a user-friendly graphical user interface. Prior to experiments, HERBS can be used to plan coordinates for implanting electrodes, targeting viral injections or tracers. After experiments, users can register recording electrode locations (e.g. Neuropixels, tetrodes), viral expression or other anatomical features, and visualize the results in 2D or 3D. Additionally, HERBS can delineate expression from multiple injections across tissue sections and obtain individual cell counts. Regional delineations in HERBS are based either on annotated 3D volumes from the Waxholm Space Atlas of the Sprague Dawley Rat Brain or the Allen Mouse Brain Atlas. HERBS allows users to scroll through the digital brain atlases and provides custom-angle slice cuts through the volumes, and supports free-transformation of tissue sections to atlas slices. Furthermore, HERBS allows users to reconstruct a 3D brain mesh with tissue from individual animals. HERBS is a multi-platform open-source Python package that is available on PyPI and GitHub.

neuroscience↗

bioRxiv2019

Action representation in the mouse parieto-frontal network

The posterior parietal cortex (PPC), along with anatomically linked frontal areas, form a cortical network which mediates several functions that support goal-directed behavior, including sensorimotor transformations and decision making. In primates, this network also links performed and observed actions via mirror neurons, which fire both when an individual performs an action and when they observe the same action performed by a conspecific. Mirror neurons are thought to be important for social learning and imitation, but it is not known whether mirror-like neurons occur in similar networks in other species that can learn socially, such as rodents. We therefore imaged Ca2+ responses in large neural ensembles in PPC and secondary motor cortex (M2) while mice performed and observed several actions in pellet reaching and wheel running tasks. In all animals, we found spatially overlapping neural ensembles in PPC and M2 that robustly encoded a variety of naturalistic behaviors, and that subsets of cells could stably encode multiple actions. However, neural responses to the same set of observed actions were absent in both brain areas, and across animals. Statistical modeling analyses also showed that performed actions, especially those that were task-specific, outperformed observed actions in predicting neural responses. Overall, these findings show that performed and observed actions do not drive the same cells in the parieto-frontal network in mice, and suggest that sensorimotor mirroring in the mammalian cortex may have evolved more recently, and only in certain species.

neuroscience↗

bioRxiv2018

Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC using cyto- and chemoarchitectural markers from Nissl-, parvalbumin- and muscarinic acetylcholine receptor M2-staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co-register the cytoarchitectural features of PPC with V1 projections. In charting the location of extrastriate areas and the architectural features of PPC in the context of each other, we reconcile different, widely used conventions for demarcating PPC in the mouse. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico-cortical connections.

neuroscience↗

bioRxiv2018

Efficient cortical coding of 3D posture in freely behaving rats

In order to meet physical and behavioral demands of their environments animals constantly update their body posture, but little is known about the neural signals on which this ability depends. To better understand the role of cortex in coordinating natural pose and movement, we tracked the heads and backs of freely foraging rats in 3D while recording simultaneously from posterior parietal cortex (PPC) and frontal motor cortex (M2), areas critical for spatial movement planning and navigation. Single units in both regions were tuned mainly to postural features of the head, back and neck, and much less so to their movement. Representations of the head and back were organized topographically across PPC and M2, and the tuning peaks of the cells were distributed in an efficient manner, where substantially fewer cells encoded postures that occurred more often. Postural signals in both areas were sufficiently robust to allow reconstruction of ongoing behavior with 90% accuracy. Together, these findings demonstrate that both parietal and frontal motor cortices maintain an efficient, organized representation of 3D posture during unrestrained behavior.

neuroscience↗