Longitudinal Two-Photon Imaging of Neurovascular Coupling in Awake and Anesthetized Marmoset Monkeys

FARE Award Winner

Authors

• CJ Kersbergen
• DK Bandy
• DC Ide
• S Choi
• AC Silva

Abstract

Transgenic marmoset models of Parkinson’s disease, Alzheimer’s disease, and schizophrenia have been successfully produced, providing a research model that closely mirrors the human conditions. However, imaging modalities that provide visualization of cellular structure and function within the cortex, and followed longitudinally over months, in this animal is not available. We herein implemented an approach to quantify vasculature, hemodynamics, and neural activity in awake marmosets using two-photon microscopy (2PM). Marmosets were acclimated to a translatable and rotatable stereotax system. A 3D-printed cranial chamber was implanted over Broadman Area 3b. AAV-GCaMP was injected into the somatosensory cortex to optically measure neural activity. After recovery, 2PM revealed vasculature, neurons, and their dynamics 500 µm below the cortical surface in awake marmosets. Normal neurovascular coupling was observed during sensory stimulation. Under isoflurane anesthesia, most prominent vasodilation occurred in capillaries and smaller arterioles, followed by larger arterioles and venules. Vascular remodeling including increased capillary density and arteriole tortuosity was observed, suggesting inflammation from implantation procedures. However, capillary connectivity from penetrating arterioles to ascending venules remained unchanged. Further, behavioral assessment before/after surgeries demonstrated no impact on cognitive and motor function. Immunohistochemistry confirmed minimal astrocyte activation with no focal damage. Over 6 months, optical penetration deteriorated due to neomembrane growth. These results demonstrate the capability to perform longitudinal 2PM imaging of cerebral microcirculation and neuronal activity in awake marmosets. This work provides a novel and insightful technique to investigate critical mechanisms in many neurological disorders in a non-human primate model without introducing confounds from anesthesia.

Scientific Focus Area: Neuroscience

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