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a) Confocal fluoroscent microscope image from human striatum showing a cholinergic interneuron (ChI, red), and a soma-to-soma "satellite" astrocyte in close apposition (Astrocyte, green). b) Schematic depiction summarizing the main results. Through this privileged interaction, striatum astrocytes can rapidly modulate neuronal excitability and downstream dopamine release through a calcium-dependent mechanism.
a) Confocal fluoroscent microscope image from human striatum showing a cholinergic interneuron (ChI, red), and a soma-to-soma "satellite" astrocyte in close apposition (Astrocyte, green). b) Schematic depiction summarizing the main results. Through this privileged interaction, striatum astrocytes can rapidly modulate neuronal excitability and downstream dopamine release through a calcium-dependent mechanism.

Glia cells are a supporting population of brain cells and are more populous than neurons, yet receive considerably less attention. One glial type – astrocytes – is thought to support neuronal networks at slow timescales from multiple seconds to minutes and hours. New research from the Cragg lab in DPAG suggests that striatal astrocytes can function potently at much faster, sub-second timescales, modulating local circuits and neuromodulation.

 

In a new paper published in Nature Communications, Jeffrey Stedehouder (Post Doctoral Research Assistant at DPAG and now Sir Henry Wellcome Postdoctoral Fellow at NDCN), Bradley Roberts (Junior Research Fellow at St John’s College, Oxford), and Cragg Group colleagues Shinil Raina, and Simon Bossi studied the effect of modulation of astrocytes in striatum on dopamine release. Unexpectedly, the authors found rapid modulation of dopamine release at sub-second timescales, mediated by acetylcholine signalling. As anatomical substrate, the authors revealed a particular soma-to-soma “satellite” configuration of astrocytes and striatal cholinergic interneurons, through which the astrocytes could rapidly modulate interneuron excitability. The paper involved broad cross-departmental collaboration, with involvement of the Oxford Parkinson’s Disease Centre at NDCN (Parkkinen lab), the MRC Brain Network Dynamics Unit at NDCN (Magill lab), as well as the Mathematical Institute (McGerty group). Together, these findings reveal a striking and powerful form of glia-neuron communication in striatum, affecting downstream circuits and neuromodulation.

 

‘This study reveals interesting novel biology with regards to striatal astrocytes, interneurons, and dopamine release,’ added Jeffrey Stedehouder, first author on the paper. ‘The peculiar satellite configuration confers potent influence of astrocytes over neuronal excitability, and the potential processing speed at sub-second timescales suggests astrocytes signal at speeds thought restricted to their neuronal counterparts. Moreover, the current findings could be of broader interest to brain disorders that present striatal dopamine dysregulation, such as Parkinson’s disease and schizophrenia.’

 

The paper “Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes” can be read here in full: https://rdcu.be/d0JNY