Considerable evidence indicates that the cholinergic input to the thalamus, which arises from the mesopontine tegmentum, plays a key role in the control of sleeping, dreaming and arousal. In addition, these cells are implicated in the normal control of locomotion and in the pathologies of Parkinson's disease, affective disorders and unconsciousness due to concussive brain injury. Nevertheless, little is known about the mechanisms controlling activity in these cholinergic afferents. The proposed experiments are designed to fill this void by providing electrophysiological evidence for interactions between the putative neurotransmitters acetylcholine, serotonin and norepinephrine on these cholinergic cells, as well as by providing evidence for synaptic control by these transmitter systems. The proposed experiments investigate the hypothesis that modulation of the biophysical properties of mesopontine cholinergic neurons is a key step in triggering alterations in behavioral state. This shall be investigated by in vitro cellular studies which will determine the cellular and synaptic properties of mesopontine cholinergic neurons and in vivo studies which will determine if alterations of these properties promote alterations in behavioral state. The results of these studies will provide the first detailed picture of the pharmacological and synaptic properties of identified mesopontine cholinergic neurons. Furthermore, by extending the analysis from the brainslice to the intact animal these studies will determine how signalling mechanisms identified in vitro function in the intact system. Accordingly, these results will have an important bearing on our understanding of brainstem mechanisms in the control of consciousness. These studies represent a first step toward the ultimate goal of understanding the neural basis of consciousness. An important future step will be to integrate these results into realistic models of brainstem and thalamic circuitry to investigate how the interplay between cellular properties and circuits generate global behavioral states.
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