The main olfactory bulb (MOB) and piriform cortex (PC) comprise a relatively simple, well characterized, sensory neural network. Our studies have shown that 40% of all locus coeruleus (LC) neurons project to MOB where they terminate with a higher degree of laminar specificity than any other forebrain target. LC-norepinephrine (NE) inputs preferentially terminate in the granule cell layer (GCL). This layer contains granule cells which are GABAergic interneurons that control the spontaneous and sensory-evoked activity of mitral cells. The mitral cell receives olfactory neuron sensory input and relays MOB output to PC. The laminar organization of LC-NE inputs to the GCL leads to specific predictions about the cellular targets and functional modulation of bulb neurons by LC-NE synapses. Preliminary studies support these predictions. Specifically, confirmed activation of LC increases the response of identified mitral cells to sensory input. We will use EM- immunocytochemical and neurophysiological methods to directly test the hypothesis that LC-NE inputs disinhibit mitral cells by direct or indirect (presynaptic) inhibition of granule cells. We will further test the hypothesis that LC-NE activation increases the signal-to-noise (S/N) ratio of sensory throughout in MOB. Our preliminary studies show that LC also massively innervates PC. The target(s) of LC-NE terminals in PC ar unknown and will be determined by localizing NE synapses on identified PC neurons intracellularly-filled in fixed slices. In vivo and in vitro physiological studies will test the hypothesis that NE modulates PC neurons so as to preserve or enhance S/N ratio gains achieved by LC-NE modulation of MOB. The long range goal of these studies is to close the gap between global hypotheses of LC-NE function and cellular-molecular studies of NE synaptic actions by characterizing LC-NE modulation of a cortically organized, integrated sensory neural network.
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