Neuronal control of appetite: investigating the role of the extracellular matrix in controlling neuronal activity in the hypothalamus

Appetite regulation is complex, and its dysregulation has serious implications for health, being observed in multiple conditions e.g., obesity, anorexia, and type 2 diabetes. Appetite regulation is governed by the interplay of biochemical and environmental cues. These cues are integrated in an area of the brain called the hypothalamus. Specifically, neural networks in the arcuate nucleus of the hypothalamus are key gatekeepers in controlling appetite, integrating hormonal, nutrient, and environmental signals to determine appetite .

Appetite follows a circadian rhythm, a natural physiological oscillation that occurs over 24-hours, dictating appetite arousal at specific time points during the day. These time points can be altered by environmental and behavioural cues, as seen in shift workers. As shift patterns change, there is a lag in appetite, with a delay before switching to the new circadian rhythm and a delay in switching back. It is thought that these changes alter the neural activity and circuitry in the arcuate nucleus but how these changes are embedded at a cellular and network level have yet to be determined as these rhythms persist beyond the lifespan of the signalling molecules themselves.

The perineuronal net is one factor which could encode these longer changes by regulating neuronal activity. The perineuronal net is a dense neuronal coat that forms on the membrane of neurons and is made up of various proteins and glycosaminoglycans. Perineuronal nets have been shown to stabilise synapses and are required for the retention of memories. Recently, they have been shown to form around neurons within the arcuate nucleus and are dysregulated in diabetes, where appetite regulation is disrupted. Together this makes them an interesting candidate for encoding the circadian rhythm of appetite at a neural circuit level.

The aim of this PhD is to investigate the role of perineuronal nets within the arcuate nucleus and interrogate their role in the regulation of appetite.

Suitable Student Qualifications

Applicants should have at least 2:1 honours degree in Biomedical science, Biological science or related degree.

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select 'Full-time PhD in Biomedical Science' as the course, and then specify the project title when prompted.

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