Biology subjects

Stedehouder, J.

Publications and source records attributed to Stedehouder, J..

4 recordsLinked to original sources

bioRxiv2026

Distinct In Vivo Electrophysiological Profiles of Mediodorsal Thalamus Subdivisions

The mediodorsal nucleus of the thalamus (MD) plays a key role in complex cognitive processes, and its dysfunction is linked to various neurological and psychiatric conditions. The MD is divided into three parts that vary in anatomical connectivity, molecular expression, and ex vivo electrophysiology. Here, we describe in vivo single-neuron electrophysiological recordings across the three MD subdivisions in head-fixed, behaving, adult, wildtype mice. We report large differences in extracellular waveforms, spiking activity, and burst firing characteristics across MD subdivisions. Specifically, central MD subdivision (MDc) neurons showed markedly increased waveform amplitude, higher spontaneous firing rate, and increased burst firing compared to medial (MDm) and lateral (MDl) subdivision neurons. Single-neuron electrophysiology features were sufficient to classify neurons into respective anatomical subdivisions. Hierarchical clustering revealed MDc is distinct from MDl and MDm and more akin to other, non-MD thalamic nuclei. Together, these data suggest distinct in vivo electrophysiological profiles of MD subdivisions, posing implications for investigating MD thalamus in health and disease.

neuroscience↗

bioRxiv2026

Higher-Order Thalamus is Pivotal in Schizophrenia-Associated Pathophysiology

Synaptic dysfunction has been proposed as cellular pathophysiology underlying schizophrenia, yet the brain-wide distribution of dysfunctional circuits at single-neuron resolution has remained unknown. Here, we perform comprehensive multi-probe electrophysiological investigations in vivo in the Grin2a+/- preclinical model for schizophrenia and control animals, recording across [~]45 brain regions spanning cortex, striatum, hippocampus, and thalamus. Mutants displayed distributed and graded alterations across regions, with prominent activity reductions in higher-order thalamus and cross-parameter alterations across prefrontal cortices, striatum, and hippocampus. Restoration of higher-order thalamic activity in mutants was sufficient to normalize alterations in connected prefrontal cortices and striatum and unexpectedly cascaded to hippocampus and sensory cortices. Thus, higher-order thalamus plays a pivotal role in schizophrenia pathophysiology and restoration of a single informed locus could present a potent therapeutic strategy.

neuroscience↗

bioRxiv2024

Brain-wide population activity during reaching integrates action-mediated goal expectation

Anticipating the outcomes of actions is central to goal-directed behaviour, but how such expectations are encoded across the brain during ongoing movement remains unclear. To address this, we recorded spiking activity from cortical and subcortical regions using multiple Neuropixels probes simultaneously in head-fixed mice performing a water-reaching task. We found that distributed neural population dynamics were strongly modulated by the availability of reward beyond their encoding of forelimb kinematics. Principal component analysis revealed conserved population dynamics across brain regions and sessions that depended on reach amplitude and reward availability. Generalized linear models revealed outcome-related encoding within region-specific population dynamics, in addition to kinematic encoding, with the strongest outcome signals expressed in frontal cortico-thalamic regions. Unsupervised cluster analysis further identified outcome-encoding subpopulations that were enriched in frontal cortices and disproportionally contributed to the shared global latent dynamics. Together, these findings demonstrate that action-mediated outcome expectations are encoded in movement-related population dynamics that are shaped by functional clusters of neurons across the brain.

neuroscience↗

bioRxiv2024

Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes

Astrocytes are increasingly thought to have underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a "soma-to-soma" satellite-like configuration not typically observed for other striatal neurons. Transient depolarization of astrocytes in mouse striatum reversibly regulated ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.

neuroscience↗