Conservation of Neuron‐Astrocyte Correlated Activity in Developing Sensory Pathways
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Abstract
Neurons in developing sensory organs exhibit prolonged burst firing before the onset of sensory experience. This activity promotes neuronal survival and maturation in central sensory pathways. Within the auditory system, periodic bursts of synaptic glutamate release activate metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in spatially and temporally correlated calcium transients; however, whether this phenomenon occurs in other sensory modalities is unknown. Using in vivo calcium imaging in the midbrain of awake mouse pups before eyelid opening, we show that retina wave‐induced burst firing of visual afferents induces correlated waves of astrocyte activity in the superior colliculus (SC), a visual processing region. Glutamate sensor imaging revealed that each neuronal burst resulted in glutamate transients at astrocyte membranes in both developing sensory regions. Calcium transients in SC astrocytes resulted from activation of astrocytic mGluR5 and mGluR3, similar to astrocyte events in the nearby inferior colliculus (IC), which are induced by neuronal burst firing in the cochlea. Astrocyte calcium increased with each neuronal wave in the SC, but only the largest neuronal events triggered astrocyte responses in the IC. Astrocyte transcriptomic analysis suggested differential expression of mGluR3 and mGluR5 between these sensory regions, in accordance with the greater dependence on mGluR5 in IC astrocytes. Despite differences in receptor contribution and temporal features of activity, astrocytes in these different regions exhibited similar overall calcium activity. Thus, neuronal burst firing in developing sensory organs provides a conserved mechanism to synchronize neuronal and astrocyte activity in the brain at a critical stage of development.
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the amplitudes of neuronal and astrocyte calcium changes were highly correlated
It looks like other waves features were correlated between neurons and astrocytes beyond amplitude, including duration. Was that indeed the case? May be other features to explore below as you look at correlations across brain regions.
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Astrocyte calcium waves from mice of this age exhibited similar properties, consisting of a continuous line of co-active astrocytes that propagated primarily in one direction, visible as diagonals in raster plots of cellular activity (Figure 1D; Movie S2).
This is a great way to visualize the waves. I'm wondering how much gap junctions contribute mechanistically to wave propagation within the developing astrocyte networks.
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To determine whether coordinated activation of neurons and astrocytes is conserved in other sensory systems, we used in vivo widefield and two-photon imaging of genetically encoded calcium indicators selectively expressed in astrocytes and neurons to define activity patterns in the SC, a visual processing region of the midbrain that receives direct retinal input.
Congrats on a beautiful, technologically impressive piece of work!
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