Research objectives and content
The histamine-containing neurones in the tuberomammillary nucleus (TM) of the posterior hypothalamus innervate most parts of the brain, and there is strong evidence that they regulate whole brain activity. The TM neurones may also modulate learning and synaptic plasticity. Dysfunction in the histaminergic system has been related to neurological disorders. TM neurones display a regular firing rate which increases during waking. It is unknown how TM firing is regulated and I plan to study these mechanisms in the laboratory of Professor Haas in Dusseldorf. The cellular mechanisms that regulate the firing rate of the TM neurones, the autoinhibitory action via H3 receptors, and the intracellular signal transduction pathways involved will be studied. Effects of other transmitters on the TM neurons and interaction with the aminergic and peptidergic systems in the hypothalamus will be studied. Electrophysiological and Ca2+-imaging methods will be used. Recording from TM neurones in brain slices will be achieved with classical electrophysiological and patch clamp procedures. Intracellular recordings with sharp electrodes will be used to establish the effects of stimulation of H3 receptors on the TM neurons. In combination with whole cell recording the intracellular Ca2+ level and its modulation will be registered.
Training content (objective, benefit and expected impact)
Very few laboratories in Finland use electrophysiological methods, although most other subdisciplines in the neurosciences, such as anatomy, pharmacology and molecular biology are well represented. The host laboratory uses the state of the art electrophysiological techniques and is renowned for its work on the physiology of the histaminergic system. If I could spend a research period there, it would be beneficial both for me and for the sake of interdisciplinarity and technology transfer.