Subcellular interactions between Ca2+ and cAMP in determining neuronal activity

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The respiratory network consists of neurons whose pacemaker and synaptic activities are critically dependent on the two second messengers, Ca2+ and cAMP. Their levels are modulated by neuronal activity through modification of properties of specific ion channels. The interactions between Ca2+, cAMP and ion channels are likely to take place in micrometer-wide subcellular domains which can be located in the vicinity of plasma membrane, mitochondria, endoplasmic reticulum and nucleus. We aim to examine these interactions in respiratory neurons by combining Ca2+ and cAMP imaging with electrophysiology. Genetically encoded fluorescent probes will be specifically expressed in neurons of organotypic slices containing the respiratory network. We will examine subcellular fluctuations of Ca2+ and cAMP levels as related to the activity of single ion channels and neuronal activity pattems and how this signalling changes during development and maturation. This knowledge is important for understanding the mechanisms controlling neuronal activity and plasticity in such vital function as breathing.