In vivo measurement of afferent activity with axon-specific calcium imaging

In vivo calcium imaging from axons provides direct interrogation of afferent neural activity, informing the neural representations that a local circuit receives. Unlike in somata and dendrites, axonal recording of neural activity-both electrically and optically-has been difficult to achieve, thus pr...

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Bibliographic Details
Published in:	Nature neuroscience 2018-09, Vol.21 (9), p.1272-1280
Main Authors:	Broussard, Gerard Joey, Liang, Yajie, Fridman, Marina, Unger, Elizabeth K, Meng, Guanghan, Xiao, Xian, Ji, Na, Petreanu, Leopoldo, Tian, Lin
Format:	Article
Language:	eng
Subjects:	Animals Axon guidance Axons Axons - physiology Axons - ultrastructure Biological transport Brain Calcium Calcium - physiology Calcium imaging Calcium ions Cells, Cultured Coding Contamination Dendrites Dendrites - physiology Dendrites - ultrastructure Female Genetic aspects Genetic code Health aspects Hippocampus - cytology Hippocampus - physiology Imaging Interrogation Kinases Localization Male Mice Neural circuitry Neuroimaging Neuroimaging - methods Neurons Neurons, Afferent - physiology Neurons, Afferent - ultrastructure Neurosciences Population genetics Presynaptic Terminals - metabolism Presynaptic Terminals - physiology Properties Protein Engineering Psychological aspects Questioning Receptors, Presynaptic - physiology Recording Sensory neurons Transportation
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Summary:	In vivo calcium imaging from axons provides direct interrogation of afferent neural activity, informing the neural representations that a local circuit receives. Unlike in somata and dendrites, axonal recording of neural activity-both electrically and optically-has been difficult to achieve, thus preventing comprehensive understanding of neuronal circuit function. Here we developed an active transportation strategy to enrich GCaMP6, a genetically encoded calcium indicator, uniformly in axons with sufficient brightness, signal-to-noise ratio, and photostability to allow robust, structure-specific imaging of presynaptic activity in awake mice. Axon-targeted GCaMP6 enables frame-to-frame correlation for motion correction in axons and permits subcellular-resolution recording of axonal activity in previously inaccessible deep-brain areas. We used axon-targeted GCaMP6 to record layer-specific local afferents without contamination from somata or from intermingled dendrites in the cortex. We expect that axon-targeted GCaMP6 will facilitate new applications in investigating afferent signals relayed by genetically defined neuronal populations within and across specific brain regions.
ISSN:	1097-6256 1546-1726