Biology subjects

Sit, T. P. H.

Publications and source records attributed to Sit, T. P. H..

3 recordsLinked to original sources

bioRxiv2025

Mecp2 deficiency impairs microscale cortical network topology and dynamics in a Rett syndrome mouse model

Rett syndrome is a debilitating neurodevelopmental disorder with cerebral processing impairments caused by MECP2 loss-of-function mutations. Mecp2-deficient mouse models reveal disruptions of microscale cortical circuits. Yet how cellular-scale information processing is altered in Mecp2-deficient microscale functional networks is unknown. We investigated the development of functional connectivity, network topology, and dynamics in microelectrode array (MEA) recordings of primary cortical cultures from Mecp2-deficient and wild-type mice. Mecp2-deficient cortical networks developed more slowly and showed decreased functional connectivity compared to wild-type, leading to smaller network size, density, and strength of connectivity. Altered network topological features in Mecp2-deficient microscale circuits predicted decreased efficiency and information-sharing capacity. This reveals developmental deficits in microscale functional networks, which may in turn underlie the cortical decline and severe cognitive disability in Rett syndrome. These findings also offer circuit-level targets and an in-vitro approach for evaluating new therapeutic products for restoring microscale network function.

neuroscience↗

bioRxiv2025

A frontal motor circuit for economic decisions and actions

Flexible behaviour requires transforming abstract cognitive representations, such as value preferences, into concrete motor actions. During economic decision-making, individuals evaluate options to guide choices and then transform these choices into specific actions to obtain rewards. Understanding how neural circuits convert these abstract economic decisions into spatial actions remains challenging because decision formation and motor planning are typically intertwined. Here we introduce a mouse task that temporally dissociates value-guided decisions from spatial action planning, and show that a frontal motor network implements the transformation across decision stages through dynamic circuit reconfiguration. Using cortex-wide imaging and optogenetic perturbations, we identified a frontal motor circuit that was causally required for both abstract and motor stages of choice. During the abstract decision stage, neurons in this circuit encoded option values and economic choices independently of sensorimotor contingencies, and unilateral silencing impaired decisions without spatial bias. In contrast, during spatial planning, value and spatial signals were non-linearly integrated to guide action selection, and unilateral silencing produced an ipsilateral bias. A dynamical model captured this transformation, predicting a mode switch from cooperative interhemispheric maintenance of economic choice to competitive, lateralized control of actions, which we validated with simultaneous bilateral recordings. These findings demonstrate how frontal motor circuits reconfigure their interactions to bridge abstract cognition and concrete actions, providing a circuit-level mechanism for flexible, value-guided behaviour.

neuroscience↗

bioRxiv2025

Different representations in layer 2/3 and layer 5 excitatory neurons of the primary visual cortex

The cortex contains multiple types of excitatory neuron, differentiated primarily by their layer of residence. We recorded from neuronal populations in the mouse visual cortex using 2-photon calcium imaging or Neuropixels probes, and found that excitatory neurons in layer 2/3 (L2/3) and layer 5 (L5) differed in their encoding of visual vs. nonvisual signals, with L2/3 more strongly modulated by visual stimuli and L5 more strongly modulated by movement. Movement had opposite effects on population synchrony in the two layers: it desynchronizes L2/3, by abolishing spontaneous synchronous fluctuations that entrain that population, and synchronizes L5, where excitatory cells are less entrained by spontaneous synchronous fluctuations and more strongly correlated with movement itself. Spontaneous activity was lower-dimensional in L2/3 than L5, with L2/3 population activity dominated by a single dimension of overlap between spontaneous and stimulus-evoked subspaces. We conclude that excitatory neurons in different layers of the visual cortex carry different representations of visual and non-visual signals.

neuroscience↗