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Heltberg, M. S.

Publications and source records attributed to Heltberg, M. S..

2 recordsLinked to original sources

Circadian Coupling Orchestrates Cell Growth

Single-cell circadian oscillators exchange extracellular information to sustain coherent circadian rhythms at the tissue level. Within cells, the circadian clock and the cell cycle couple, yet the mechanisms governing this interplay remain poorly elucidated. Here, we study the role of extracellular circadian communication in the intracellular coordination between the circadian clock and the cell cycle. We demonstrate that the loss of extracellular circadian synchronization disrupts circadian and cell cycle coordination within individual cells, impeding collective tissue growth. Coherent circadian rhythms yield oscillatory growth patterns, unveiling a global timing regulator of tissue dynamics. Knocking down core circadian elements abolishes observed effects, highlighting the central role of circadian clock regulation. Our research underscores the significance of tissue-level circadian disruption in regulating proliferation, thereby linking disrupted circadian clocks with oncogenic processes. These findings illuminate the intricate interplay between circadian rhythms, cellular signaling, and tissue physiology, enhancing our understanding of tissue homeostasis and growth regulation in both health and disease contexts.

cell biology↗

Local changes in potassium ions modulate dendritic integration

During neuronal activity the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, but it remains unclear what role these [K+]o changes play in dendritic integration of synaptic inputs. We used mathematical formulations and biophysical modeling to explore the role of activity-dependent K+ changes near dendritic segments of a visual cortex pyramidal neuron, receiving synaptic inputs tuned to stimulus orientation. We found that the fine-scale spatial arrangement of inputs dictates the magnitude of [K+]o changes around the dendrites: Dendritic segments with similarly-tuned inputs can attain substantially higher [K+]o increases than segments with diversely-tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input-output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results suggest that local activity-dependent [K+]o changes around dendrites may act as a "volume knob" that determines the impact of synaptic inputs on feature-tuned neuronal firing.

neuroscience↗