Biology subjects

Beenhakker, M.

Publications and source records attributed to Beenhakker, M..

3 recordsLinked to original sources

bioRxiv2026

Spike-wave discharges reflect widespread, but non-uniform, cortical hypersynchrony during immobility

Spike-wave discharges (SWDs) are the electrographic hallmark of absence epilepsy, yet direct evidence for their proposed basis in cortical hypersynchrony has been scarce. We addressed this gap by recording neuronal populations across three cortical regions - primary somatosensory (S1), visual (V1), and secondary motor cortex (M2) - using silicon probe arrays in spontaneously seizing C3H/HeJ mice. SWDs drove profound increases in neuronal synchrony, rhythmicity, and phase-locking across all recorded regions. V1 and M2 neurons were clearly entrained to SWD cycles, though less strongly than S1 neurons. Electrical stimulation of both S1 and V1 could induce or terminate SWDs, supporting widespread network involvement. Finally, we also provide evidence that SWD-associated reductions in firing rate could be attributable to co-occurring behavioral immobility rather than to the seizures themselves.

neuroscience↗

bioRxiv2025

Thalamic hubs as early sources of global neuronal synchrony in absence epilepsy

Generalized seizures reflect a pathological state of sudden, global neuronal hypersynchrony. The mechanisms that support the initiation and maintenance of such synchrony remain unknown. Using simultaneous single-unit and electrocorticographic recordings in two mouse models of absence epilepsy, we evaluated the activity of approximately 2,000 individual neurons across 26 brain structures. By doing so, we resolved the temporal progression of single neuron activity prior to and during generalized seizures. Surprisingly, we observed that rhythmic, synchronized activity emerges early and gradually in both thalamus and cortex. Moreover, while we observe that individual neurons across most structures fire rhythmically and synchronously during seizures, a small subset of midline thalamic nuclei display activity that is strongly correlated across multiple regions. Finally, disturbing neuronal activity within the midline thalamus terminates seizures. Thus, our findings collectively highlight the possible role of the midline thalamus in emergence of neuronal hypersynchrony.

neuroscience↗

bioRxiv2021

Extracellular cues accelerate neurogenesis of induced pluripotent stem cell derived neurons

Neurogenesis is a complex process encompassing neuronal progenitor cell expansion/proliferation and differentiation, followed by neuron maturation. In vivo models are most commonly used to study neurogenesis; however, human induced pluripotent stem cell-derived (iPSC) neurons are increasingly used to establish cellular models of human neurological processes. Unfortunately, the differentiation and maturation of iPSC-derived neurons varies in methodology, is asynchronous, and has restricted experimental utility because of extended differentiation/maturation times. To accelerate and standardize iPS neuronal maturation, we differentiated and matured feeder layer-free iPSC-derived neuronal cultures under physiological oxygen levels (5%), and modified the underlying extracellular matrix and medium composition. Our results demonstrate that calretinin gene expression occurred earlier under our optimized iPS conditions and the corresponding "neurogenesis burst" associated with proliferative expansion occurred more synchronously, reliably emerging two and three weeks after differentiation. As expected, the expression of mature neuronal markers (i.e., NeuN+/Calbindin+) started at 4-weeks post-differentiation. qPCR microarray, western blot and single cell analyses using high content imaging indicated that 4-week iPS neuronal cultures were non-cycling with decreased expression of cyclin D1 and Ki67. Our data demonstrate that extracellular cues influence the kinetics of neurogenesis models and that feeder layer-free iPSC-derived neurogenesis can be reproducibly miniaturized.

neuroscience↗