Neuroscientists expand a chemogenetic approach to provide insight into brain neural circuitry

A novel method for understanding the function of neural pathways has been developed by neuroscientists from The Florey and the University of Melbourne.

Expected to have widespread applications across brain research, the technique could help reveal new information about the brain.

Unravelling the complexity of neural circuitry in the mammalian brain is a major goal in neuroscience research.

“While approaches have been developed that enable regulation of neuronal activity using light (optogenetics) or designer drugs (chemogenetics), neither of these techniques provide information about the neuronal connections responsible for controlling the neuron’s activity,” said Professor Andrew Allen from the University of Melbourne.

“Finding an approach able to do this may unlock questions that still puzzle neuroscientists, such as what causes a cell group to become active during a particular behaviour or disease state?” he added.

Published today in Cell Reports, Professors Ross Bathgate and Andrew Allen, with their team of researchers, have developed and validated a method that takes chemogenetics one step further.

“Using a viral vector delivery system, we were able to ‘engineer’ neurons to express a normally inactive insect neuropeptide, called allatostatin, to turn chemogenetic allatostatin receptors ‘on’ or ‘off’ in a specific cell group. By controlling which neurons express allatostatin and its receptor, we’re able to map the neural circuitry connecting cell groups and, most importantly, understand how that circuit is working to control particular behaviours,” explained Professor Bathgate from The Florey.

The team took the approach to an animal model where they inhibited neural pathways known to relay information from the gastrointestinal tract to the brain to regulate body weight control. The animals showed reduced body weight for the length of the study, validating the chemogenetic approach and demonstrating its potential to control neuronal circuit function long term. This opens further prospects to understanding how obesity might be treated.

“No doubt this technique has applications beyond what we currently realise that will shed light on many different neural systems in health and disease states. We hope it is picked up and used widely in the science community to make further discoveries,” said Professor Bathgate.

The research was supported by grants from the Australian National Health and Medical Research Council and the Australian Research Council, and received support from the State Government of Victoria’s Operational Infrastructure Support Program. It has been published in Cell Reports. DOI: 10.1016/j.celrep.2020.108139.

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