Neuromodulatory, circuit, and glial mechanisms of rapid changes in sensory processing

Abstract:
Information processing in the brain undergoes dramatic shifts across behavioral states, yet the cellular mechanisms driving these transitions remain poorly understood. We investigated how changes in alertness and activity levels modulate neural circuits by examining the spatial and temporal dynamics of key neuromodulators—acetylcholine and norepinephrine—and their effects on both neurons and astrocytes in the cerebral cortex. Using optical sensors for calcium, voltage, and neurotransmitters, we captured rapid modulation of neural activity, including both spiking and subthreshold dynamics, across different states of arousal in quietly awake mice. While the subthreshold changes in neuron voltage are known, surprisingly, we also discovered that astrocytes undergo substantial voltage fluctuations across brain states—changes that may influence critical downstream processes including neurotransmitter uptake. These optical techniques reveal that even subtle shifts in alertness trigger coordinated, state-dependent changes in neuromodulators and both neuronal and glial activity, providing new insights into the cellular basis of brain state regulation.

About the Speaker:
The Reimer Lab studies how brain state transitions influence neural circuit dynamics and sensory processing, using imaging and electrophysiology approaches. Dr. Reimer completed his graduate work at the University of Chicago with Nicho Hatsopoulos, focusing on motor control in behaving primates. As a postdoc with Andreas Tolias at Baylor College of Medicine, Dr. Reimer showed that pupil size fluctuations can track brain state changes in mice, helping establish this species as a useful model for studying arousal-dependent effects on neural activity.

Dr. Reimer led the functional calcium imaging components of the IARPA MICrONS project and his lab developed NEURD, a computational pipeline for automated proofreading and feature extraction from large electron microscopy datasets. The lab's MICrONS work helped reveal a "general wiring rule" in mouse visual cortex, demonstrating that neurons with similar response properties are more likely to be synaptically connected across multiple visual areas.

Current research examines how acetylcholine and norepinephrine influence cellular and circuit activity during sensory processing in both healthy and disease contexts. Additionally, the lab is studying changes in neuromodulator dynamics across the lifespan and in Alzheimer's disease. Finally, the lab is also investigating astrocyte dynamics, exploring their roles in brain state regulation through both calcium and voltage signaling.

Contact

  Grayson Sipe
  gsipe@psu.edu