About
In this webinar, Alexey Semyanov, PhD, and Amit Agarwal, PhD, present their work on activity and calcium signaling in neurons, astrocytes, and oligodendrocyte precursor cells (OPCs) during exploratory locomotion behavior in awake and head-fixed mice.

Orchestrated activation of different cell types and their interactions within the brain active milieu provide the cellular basis for brain functions. For example, in mice locomotion triggers a coordinated response of both neurons and astrocytes in various brain regions. In the first part of the webinar, Dr. Semyanov presents his research on calcium (Ca2+) imaging in the somatosensory cortex of awake and head-fixed mice on the airlifted Neurotar platform, including the relationship between localized Ca2+ activity in different cell types and locomotor activity. These results demonstrate that the neuronal Ca2+ response is primary, reflecting sensory input processed by neurons, while astrocytic Ca2+ dynamics are secondary and likely to provide metabolic and homeostatic support of intercellular communication and plasticity within the brain active milieu.

In the second portion of the webinar, Dr. Amit Agarwal presents his work on oligodendrocyte precursor cells (OPCs). Although OPCs mainly generate oligodendrocytes and contribute to myelination, they also form synapses and actively communicate with neurons. Yet, how OPCs translate distinct modes of neuronal signals into cellular signals remains unknown. Dr. Agarwal presents his research addressing this question, including the generation of a triple transgenic mouse line expressing a green genetically encoded Ca2+ sensor (GCaMP6f) and red cytosolic cell-morphology reporter (tdTomato) in OPCs. The data obtained using two-photon microscopy through a chronic cranial window in the somatosensory cortex of these awake mice allow for concomitant calcium imaging and fate-tracking, and together with gene expression studies, pharmacological analysis, and locomotor activity reveal a role for norepinephrine as a potent regulator of OPC fate.

Key Topics:

  • Optical imaging methods to simultaneously record Ca2+ signals and track cell-fate in brain

  • Machine-learning based automatic analysis of Ca2+ signals (CaSCaDe) and exploratory locomotion behavior

  • Neurons and glial cells (e.g., astrocytes and OPCs) respond to locomotion by elevations of intracellular calcium

  • Astrocytes and OPCs Ca2+ responses are delayed relative to neuronal activation

  • Astrocytes possess integrative function – Ca2+ elevations start in distal processes and propagate to soma, where the Ca2+ response amplifies and develops into oscillations

  • Cell-type specific chemogenetic manipulation of Ca2+ activity in neurons and glia

  • Neuromodulators such as norepinephrine regulate differentiation of OPCs into myelinating oligodendrocytes

Presenters
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Alexey Semyanov, PhD
Professor/Director
Prof. Alexey Semyanov did his postdoctoral research in the labs of Profs. Dimitri Kullmann and Dmitri Rusakov at University College London (UK) from 1998 to 2004. During this period he studied extrasynaptic signalling mediated by glutamate and GABA escaping synaptic cleft (spillover). Then he moved to RIKEN Brain Science Institute (Japan) where he established own lab in 2005. He continued his research of extrasynaptic signalling, and described the excitatory effects of tonic GABAA receptor-mediated conductance. He also investigated signalling mediated by local changes in extracellular K+ concentrations and started research on astrocytic physiology. In 2014, Alexey moved to Russia where he studied neuron-glia interactions and suggested an integrative concept of the brain active milieu. Now, Prof. Semyanov is a Director of the Neuroscience center at Jiaxing University (China).
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Amit Agarwal, PhD
Chica and Heinz Schaller Research Group Leader
Dr. Amit Agarwal is the Chica and Heinz Schaller Research Group Leader at the Institute for Anatomy and Cell Biology, Heidelberg University, Germany. He received his Ph.D. in neurosciences at the Max-Planck Institute of Experimental Medicine, Goettingen, Germany. He performed his post-doctoral training in glial cell physiology from 2010 to 2017 in the Department of Neuroscience at Johns Hopkins University, USA. The Agarwal laboratory uses optical and electron microscopic techniques, single-cell genetics, mouse transgenics, multi-omics approaches, and computational methodologies to decipher cellular connectivity and molecular pathways by which neurons and glia (e.g., astrocytes and oligodendrocytes) interact, interconnect and integrate into the brain. The focal aim of his laboratory is to understand the functional role of neuron-glia and glia-glia connectivity in the neural circuits function and neurometabolism. His lab studies how disruptions in such cell-cell interactions contribute to the pathophysiology of neurodegenerative and psychiatric disorders, including multiple sclerosis and autism.
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