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Updated: Jun 22, 2025
Simultaneous Imaging of Microglial Dynamics and Neuronal Activity in Awake Mice
Published on: August 23, 2022
Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse
Péter Berki1,2,3, Csaba Cserép4, Zsuzsanna Környei4
1János Szentágothai Doctoral School of Neuroscience, Semmelweis University, Budapest, H-1083, Hungary.
Abstract:
Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.
Insights
Microglia, the brain’s immune cells, change over time in acute brain slices. These dynamic microglia modulate neuronal networks and synapse health, crucial for understanding brain function.
Area of Science:
- Neuroscience
- Neuroimmunology
- Cellular Biology
Background:
- Acute brain slices are vital for studying the central nervous system (CNS).
- Microglia, the resident immune cells of the CNS, act as damage sensors.
- The response of microglia to slice preparation and their impact on neuronal activity ex vivo remain incompletely understood.
Purpose of the Study:
- To investigate microglial phenotypes and their contribution to network organization and functioning in acute brain slices.
- To elucidate the role of microglia in shaping neuronal activity and synapse dynamics ex vivo.
Main Methods:
- Analysis of microglial phenotypes in acute mouse brain slices over time.
- Investigation of extracellular ATP dynamics and P2Y12R and CX3CR1 signaling pathways.
- Assessment of microglia-neuron interactions and synapse numbers.
- Functional assays to evaluate the impact of microglia on neuronal network activity.
Main Results:
- Microglial phenotypes exhibit time-dependent changes in acute brain slices, influenced by extracellular ATP dynamics.
- P2Y12R downregulation and altered microglia-neuron interactions correlate with changes in excitatory and inhibitory synapses.
- Functional microglia promote synapse sprouting, whereas microglial dysfunction impairs network activity (ripple activity).
Conclusions:
- Microglia are critical modulators of neuronal networks, maintaining network integrity and activity.
- Acute brain slice preparation can serve as a model to study time-dependent microglia-neuron interactions.
- Understanding these interactions is vital for modeling physiological and pathological conditions in the CNS.
