Histological and functional characterization of sleep-active cortical neurons in rats

• Applicant: Dr. Lars Dittrich
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 193394489

It is widely accepted that sleep is regulated not only by a circadian process, i.e. we find it easier to sleep at night than during daytime, but also by a homeostatic process, i.e. we experience long waking times as tiring and need sleep to recover. However, the neural mechanisms underlying homeostatic sleep regulation are not well understood. Recently, a population of cortical interneurons were discovered that are active during sleep but not during wake. The fact that the activity of these neurons is correlated to slow-wave-activity, a marker for sleep need, suggests that they are involved in homeostatic sleep regulation. They can easily be identified by their immunoreactivity for the enzyme neuronal nitric oxide synthase (nNOS). In the proposed project, I will elucidate how these neurons are modulated and what functions they have for sleep-homeostasis and sleep in general. To this end, I will follow three parallel approaches. 1) I will investigate which receptors they bear. Linking to existing literature, I will focus on receptors for acetylcholine and substance P. 2) To find out more about how they are regulated, I will test whether they are activated by select pharmacological substances that induce sleep or anesthesia by distinct pharmacological mechanisms. 3) I will test the effects of targeted stimulation and ablation of these neurons on sleep homeostasis and cortical activity during sleep. Specificity of stimulating and toxic compounds will be achieved by conjugation with substance P, for which the targeted neurons bear a receptor. The insights we will gain from the proposed experiments will enhance our understanding of how sleep is regulated and may have implications for sleep disorders such as insomnia and sleep disturbances associated with other neurological or psychiatric disorders.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Thomas S. Kilduff, Ph.D.