Multiphoton Microscopy Webinars

In Vivo Imaging of Microglia as the Brain’s Thermostat for Tuning Neuronal Activity

presented by Dr. Mario Merlini, Junior Team Leader at the Blood & Brain @ Caen-Normandie Institute

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Submit the form for instant, full-length access to this webinar and related resources. In this webinar, Dr. Mario Merlini (Junior Team Leader at the Blood & Brain @ Caen-Normandie Institute) discusses his latest research and findings using two-photon microscopy for high-resolution imaging of brain cells.


Learn how in-vivo two-photon imaging reveals new information about neuronal hyperexcitability.

  • Gain new insight into the advantages of in-vivo two-photon imaging for the study of microglial regulation of neuronal activity.
  • Explore the two-photon imaging methods used — including simultaneous in-vivo imaging of microglia and neuronal activity — as well as the techniques used to complement these methods, like neurotransmitter uncaging, whisker stimulation, and EEG recording.
  • Understand what this study reveals about the role of microglia dynamics in neuronal hyperexcitability.
  • Hear our guest speaker answer audience questions about his research, including essential considerations for experimental design.
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Presenter's Abstract

Prevention of neuronal hyperexcitability is essential for healthy brain function, as is illustrated by the aberrant, hyperexcited neuronal activity that contributes to cognitive dysfunction in neurodegenerative diseases and several psychiatric disorders. In this webinar, I will describe recent data acquired with awake in vivo two-photon imaging, in vivo EEG recordings, two-photon-induced glutamate uncaging, and 3D reconstructions of scanning block-face electron microscopy in a newly developed mouse model of chronically impaired microglia motilities.

These mice have hypersynchronized neuronal activity that induces a severe seizure phenotype. The findings reveal a unique role for microglia dynamics in maintaining evoked neuronal activity within a physiological range to prevent brain hyperexcitability, identifying microglia as thermostat-like cells in the regulation of brain activity. I will further present the development of the automated whisker stimulus tool and its integration in a synchronized in vivo two-photon time-lapse image acquisition workflow, as was used in this study for the simultaneous imaging of microglia motilities and evoked intraneuronal Ca2+ transients in awake, head-fixed mice.

Read more about Dr. Merlini's in-vivo two-photon imaging, ablation, and glutamate uncaging experiments on microglia in our latest Fluorescence Microscopy Journal Club.

Guest Speaker

Mario Merlini, Ph.D.
Junior Team Leader, Blood & Brain @ Caen Normandie Institute, INSERM U1237, GIP Cyceron, Caen, France

Dr. Mario Merlini is a Junior Team Leader at the Blood & Brain @ Caen Normandie Institute, integrated within the French National Institute of Health and Medical Research (INSERM) and hosted by the biomedical imaging platform Cyceron in Caen, France. He received his Ph.D. degree in neuroscience from the University of Zurich, Switzerland, in the lab of Dr. Roger M. Nitsch studying cerebrovascular and astrocytic pathologies contributing to cognitive impairment in Alzheimer’s disease.

Dr. Merlini was awarded a Swiss National Science Foundation Postdoctoral Fellowship to pursue his postdoctoral research at the Gladstone Institute of Neurological Disease, San Francisco, USA with Dr. Katerina Akassoglou. There, he used in vivo two-photon imaging and 3D imaging in cleared brains to discover a mechanistic link between compromised blood-brain barrier integrity, microglia activation, and dendritic spine loss in Alzheimer’s disease, as well as a fundamental, physiological role for microglia dynamics in tuning neuronal activity. He also developed sensory stimulation and EEG recording methods for application in in-vivo two-photon brain imaging in awake mice. As an independent PI, Dr. Merlini applies his expertise in functional and structural in vivo imaging of glial dynamics, cerebral blood flow, and neuronal activity in experimental animal models and human brains to investigate neurovascular pathways underlying psychiatric disorders and, more fundamentally, how neurovascular interactions shape cognition.