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Tuesday, July 21 • 3:30pm - 4:00pm
W2 S08: Multiphoton imaging of calcium signals in populations of hippocampal neurons during behaviour in mouse models of neurodegenerative disorders

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The hippocampus plays an important role in learning, memory, and spatial navigation, impairments of which are typically among the first symptoms of Alzheimer’s Disease. Structural abnormalities, amyloid plaques, and aberrant neuronal excitability appear in disease-affected hippocampi, resulting in abnormal activity visible through multiphoton calcium imaging of the hippocampus. We imaged calcium signals in populations of CA1 hippocampal neurons in 5xFAD transgenic mice and wild-type littermates following viral transduction of the hippocampus with hSyn1-GCaMP6s-mRuby. Mice were head-fixed and trained to run along a circular linear track lined with visuotactile cues, floating on an air table (Neurotar Ltd). The three-dimensional distribution of amyloid plaques was mapped following i.p. injection of Methoxy-X04 by acquiring depth stacks at 720 nm excitation. On each imaging session on subsequent days, calcium signals were monitored in several hundred CA1 neurons within 500 x 500 µm field of view. We took advantage of the activity-independent red channel (mRuby) information for motion-correction using a non-rigid deformation algorithm. Imaging files were collected in 4 min sections, for ~20 min periods in which the mouse ran in a single environment; several environments were imaged per session. Regions of interest corresponding to individual neurons were cross-registered across files, environments, sessions and days, within some cases cells being tracked through imaging sessions for up to 14 days. We were able to observe features of CA1 activity reminiscent of electrophysiological recordings in freely moving animals, including well-defined place fields, phase-precession of place fields, and place field remapping. In contrast, place fields in a two-dimensional version of the task were impoverished, presumably due to the lack of vestibular input in the head-fixed preparation. In ongoing work, we are using this preparation to study the circuit basis of impairments in learning and memory in the 5xFAD model, as well as to test therapeutic strategies.


Tuesday July 21, 2020 3:30pm - 4:00pm CEST
Crowdcast (W02)