Biology subjects

Milton, R.

Publications and source records attributed to Milton, R..

5 recordsLinked to original sources

bioRxiv2026

Locomotor activity enhances environmental representation by boosting visuo-frontal communication

During environment exploration we rapidly acquire visual information to identify targets of interest. Here, we discovered that locomotion limits how long natural scenes are viewed dur- ing free exploration. Whether the brain has developed compensatory mechanisms to ensure that sensory information is accurately transmitted to downstream areas during and after locomotion is unknown. We examined this issue by recording the spiking activity of popula- tions of neurons in visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while macaques moved freely to explore their environment or performed treadmill bipedal locomotion. The communication between visuo-frontal cortical areas was enhanced during and after locomotion to increase visual-evoked responses and population coding accuracy in prefrontal, but not visual cortical neurons. This in turn improved behav- ioral performance in a freely moving visual detection task after locomotion. Electrical stim- ulation further revealed elevated inter-areal synaptic efficacy during locomotor activity. The mechanism whereby locomotion enhances stimulus coding accuracy in prefrontal cortex and behavioral performance by increasing visuo-frontal communication is functionally beneficial during environmental exploration when incoming stimuli are rapidly changing and the win- dow for perceptual decisions is temporally restricted.

neuroscience↗

bioRxiv2026

A claustro-cortical loop times state transitions for flexible behavior

Metastable dynamics, in which neural activity moves between transiently stable patterns, have been proposed to underlie the real-time coordination on which the brains cognitive and behavioral functions depend1-3. In the cortex, the simplest form of this regime is the alternation between active UP states, in which neurons fire, and silent DOWN states, in which firing is strongly reduced, a bistable architecture that shapes how afferent information is processed 4-8. Such metastable dynamics are ubiquitous across cortex 9,10, yet how their state transitions are timed and controlled, and how this timing shapes behavior, remain open questions. Here we show, in freely behaving mice performing a cue-guided switching task, that the metastable dynamics of frontal cortex are jointly shaped by its reciprocal loop with the claustrum, a small and widely connected subcortical structure, and that the loops timing of these state transitions is required for efficient flexible behavior. Claustrum activity led the cortical UP-to-DOWN state transition, delivering to anterior cingulate cortex a low-dimensional drive aligned with the axis along which the cortical state switches. This drive was carried not by a rise in claustral firing but by transient coordination: population synchrony peaked at the transition even as mean rate fell. Silencing ACC-projecting claustrum terminals reduced directed claustro-cortical coupling, biased cortex away from the DOWN state by prolonging UP states and shortening DOWN states, and selectively impaired cue-driven switching while sparing exploratory foraging. These results place flexible behavior under the control of a defined cortico-subcortical loop that times cortical state transitions, offering a circuit-level entry point into the cognitive rigidity of many psychiatric and neurological conditions11-13.

neuroscience↗

bioRxiv2025

Inhibiting disulphide bonding in truncated tau297-391 results in enhanced self-assembly of tau into seed-competent assemblies.

Tau undergoes fibrillogenesis in a group of neurodegenerative diseases termed tauopathies. Each tauopathy is characterized by tau fibrils with disease-specific conformations, highlighting the complexity of tau self-assembly. This has led to debate surrounding the precise mechanisms that govern the self-assembly of tau in disease, especially the involvement of disulphide bonding (DSB) between cysteine residues. In this study, we use a truncated form of tau, dGAE, capable of forming filaments identical to those in disease. We reveal the impact of DSB in dGAE assembly and propagation by resolving the global mechanisms that dominate its assembly. We found evidence for surface-mediated secondary nucleation and fragmentation being active in dGAE assembly. The inhibition of DSB during dGAE assembly leads to an enhanced aggregation rate through a reduced lag phase, but with no effect on the global assembly mechanisms. We suggest this is due to the formation a dominant, seed-competent species in the absence of DSB that facilitates elongation and secondary nucleation resulting in enhanced assembly. In vitro seeding assays reveal the recruitment of endogenous tau in a cell model only when using dGAE species formed under conditions that inhibit DSB. Our results further support the use of the in vitro dGAE tau aggregation model for investigating the mechanism of tau assembly, the effect of varying conditions on tau assembly and how these conditions affect the resultant species. Further studies may utilise dGAE and its aggregates to investigate tau seeding, propagation and to highlight or test potential targets for therapies that reduce the spread of pathologic tau throughout the brain.

biochemistry↗

bioRxiv2024

Divergent Subregional Information Processing in Mouse Prefrontal Cortex During Working Memory

Working memory (WM) is a critical cognitive function allowing recent information to be temporarily held in mind to inform future action. This process depends on coordination between key subregions in prefrontal cortex (PFC) and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout the phases of WM using electrophysiological recordings in freely-moving animals, particularly mice. To this end, we recorded single-units in three neighboring medial PFC (mPFC) subregions in mouse - supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC) - during a freely-behaving non-match-to-position WM task. We found divergent patterns of task-related activity across the phases of WM. The MOs is most active around task phase transitions and encodes the starting sample location most selectively. Dorsomedial PFC contains a more stable population code, including persistent sample-location-specific firing during a five second delay period. Finally, the vmPFC responds most strongly to reward-related information during the choice phase. Our results reveal anatomically and temporally segregated computation of WM task information in mPFC and motivate more precise consideration of the dynamic neural activity required for WM.

neuroscience↗

bioRxiv2022

Adaptive coding across visual features during free-viewing and fixation conditions

Theoretical studies have long proposed that adaptation allows the brain to effectively use the limited response range of sensory neurons to encode widely varying natural inputs. However, despite this influential view, experimental studies have exclusively focused on how the neural code adapts to a range of stimuli lying along a single feature axis, such as orientation or contrast. Here, we performed electrical recordings in macaque visual cortex (area V4) to reveal significant adaptive changes in the neural code of single cells and populations across multiple feature axes. Both during free viewing and passive fixation, populations of cells improved their ability to encode image features after rapid exposure to stimuli lying on orthogonal feature axes even in the absence of initial tuning to these stimuli. These results reveal a remarkable adaptive capacity of visual cortical populations to improve network computations relevant for natural viewing despite the modularity of the functional cortical architecture.

neuroscience↗