At Japan’s University of Tsukuba, Professor Takeshi Sakurai runs a laboratory involved in the discovery of neuropeptides and elucidation of their functions, and is Vice Director of the International Institute for Integrative Sleep Medicine (IIIS). Sakurai explains: ‘Neurotransmitters
are the means by which different parts of the brain talk to one another. They comprise small molecules that fit into receptors and activate or inhibit the receiving neurons.’ His main interest is in the deep brain region that regulates the basic functions of animals, including sleep,
emotions, eating and memory formation. He and his team are involved in a number of projects, including a multi-agency national initiative called Willdynamics, which is funded by Kakenhi and JSPS, and is exploring the mechanisms behind willpower or motivation. At the Sleep Institute, the role
of neurotransmitters such as orexin are being studied to reveal their role in sleep disturbances. Sakurai’s team look for neuropeptides and investigate their functions and signalling pathways by a variety of methods, including reverse pharmacology and molecular cloning. He says: ‘A
fairly new investigative method called optogenetics is also proving very useful. We used genetically modified mice, which express light sensitive ion channels that can be activated through the delivery of light through fine fibre optic cables. The mice are free to run and interact with one
another as they would normally during these experiments.’ Researchers can also introduce light sensitive proteins to particular parts of the brain using genetically-modified viruses as carriers. The object of these studies is to determine the precise function of particular neurotransmitters
and pathways. Recent findings suggest that orexin is implicated in many of the brain’s basic functions. For instance, one experiment revealed that a loud sound triggered orexin activity in mice that had been conditioned to exhibit a fear response to such a sound. The orexin activated
noradrenergic neurons, which in turn triggered reactions in the amygdala, which is the centre for regulating emotions such as flight, fight or freeze. When orexin receptors were blocked by an antagonist, the same mice exhibited fewer fear symptoms in response to the sound. Sakurai adds: ‘We
found that if we over-stimulated the orexin neurons, the animals would exhibit a fear response to similar sounds that were not threatening. This mechanism could be behind generalised fear conditions such as PTSD, which are initiated by traumatic experiences.
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