Brain State Control
Lead Research Organisation:
University of Manchester
Department Name: Life Sciences
Abstract
Everyday a clock in your brain instructs a switchboard to the tell rest of the brain and body that it is time to arouse from the night's slumber. Without this wake-up call or the switchboard operator, you cannot function properly and fall asleep at the wrong times of the day. Recently, we found that messages from switchboard operator can reset this daily alarm clock, and while we have identified some of the words, we do not yet fully comprehend the language of this operator. In our research we are seeking to understand how the switchboard operator and the daily clock converse to communicate the wake-up call throughout the brain.
Technical Summary
Determining how neural circuits interact in the timed switching of brain and behavioural states is a key problem in neuroscience. We know that the circadian system is important near 24h organization of brain and behaviour and that orexin neurons in the lateral hypothalamus (LHA) are key components of a neural system vital for promoting arousal, but little is known about how these brain systems interact. Here we use techniques and models that have been highly successful in the study of circadian clocks and orexin neurons respectively and combine them to identify the mechanisms by which LHA/orexin signalling alters cellular activity in key structures of the brain's circadian system, determine whether targeted impairment of orexin signalling affects circadian function and if so, how this comes about, and finally determine how signals from the circadian system affect LHA/orexin neuronal activity. These investigations will provide unique insights into the bases for brain state control.
Organisations
Publications
Belle MD
(2014)
Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Belle MD
(2009)
Daily electrical silencing in the mammalian circadian clock.
in Science (New York, N.Y.)
Scott F. F.
(2010)
Electrophysiological Effects of Melatonin on Mouse
Per1 and non-
Per1 Suprachiasmatic Nuclei Neurones
In Vitro
in JOURNAL OF NEUROENDOCRINOLOGY
| Description | In this research, we discovered that clock cells in the brain show very unusually properties. They can survive and function in very excited states that ordinarily lead to brain cell death. Further, we found that these states only occurred during the day, with the cells entering conventional states during the night. Through collaboration with mathematicians in the US, we were able to show that models of clock cells could replicate the experimental findings. This has lead to a new understanding of how molecules that compose the circadian clock function to alter the electrical properties of brain clock cells. We subsequently showed how hormones (melatonin) and an arousal associated brain chemical, orexin, affect these excited clock cells. From these, we identified novel mechanisms of excitability of clock cells and their resetting by external molecules. |
| Exploitation Route | The research showed that our understanding of the molecular daily clock and its control of the brain cell activity is very much in its infancy. Our work has demonstrated that brain clock cells have unique and unusually properties and has lead to new models of clock cells. Further, we also identified specific events in the membranes of clock cells and these findings could be pursued by pharmaceutical firms interested in developing new compounds to combat disorders of circadian timekeeping. |
| Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |