Hosted by the Circuit Neuroscience research group (CNS)

Synapses are nanoscale signalling machines with a complex molecular architecture. Astrocytes, the support cells of the nervous system, make specialised contacts with synapses, termed tripartite synapses. It is here at tripartite synapses that astrocytes are capable of responding to neural network activity and in return signal back to modulate synaptic activity, and thus manipulate behaviour. Understanding the mechanisms by which astrocytes modulate neuronal activity at the tripartite synapse is of considerable importance to our basic understanding of neurophysiology in health and disease. To investigate astrocyte interactions within neuronal networks and tripartite synapse nanostructure, I utilise a range of genetically engineered mouse models and microscopy techniques, including Ca2+ imaging and super-resolution microscopy, in combination with electrophysiology, pharmacology and pharmacogenetics. I will present data from two recently published studies that: 1) identify the mechanisms by which astrocytes modulate locomotor activity in the spinal cord (Broadhead & Miles, 2020, Front. Cell. Neurosci.), and 2) visualise the nanostructure of tripartite excitatory synapses in the mouse spinal cord (Broadhead et al., 2020, Sci. Rep.). In brief, these studies reveal that astrocytes use purinergic signalling to modulate fictive locomotion in the mammalian spinal cord and their activity is driven by neuronal glutamatergic signalling via mGluR5 receptor activation. Furthermore, synapses which are contacted by astrocytes are nanostructurally larger and more enriched with postsynaptic scaffolding protein PSD-95. Finally, I will present preliminary data on a large-scale microscopy investigation visualising tripartite synapses throughout the lumbar spinal cord in mouse models of Amyotrophic Lateral Sclerosis.

• Join Zoom Meeting: https://bristol-ac-uk.zoom.us/j/93724744352?pwd=ZVRDQzJLWmNLWW5GR2hPNlB0bVdsZz09 
• Meeting ID: 937 2474 4352
• Passcode: 217191