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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC002588-01
Application #
2128032
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1994-06-01
Project End
1998-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Hayar, Abdallah; Karnup, Sergei; Ennis, Matthew et al. (2004) External tufted cells: a major excitatory element that coordinates glomerular activity. J Neurosci 24:6676-85
Karnup, S V (2004) Membrane and network theta-rhythm generation in hippocampal slices. Zh Vyssh Nerv Deiat Im I P Pavlova 54:32-43
Hayar, Abdallah; Karnup, Sergei; Shipley, Michael T et al. (2004) Olfactory bulb glomeruli: external tufted cells intrinsically burst at theta frequency and are entrained by patterned olfactory input. J Neurosci 24:1190-9
Coolen, Lique M; Veening, Jan G; Petersen, Daniel W et al. (2003) Parvocellular subparafascicular thalamic nucleus in the rat: anatomical and functional compartmentalization. J Comp Neurol 463:117-31
Coolen, Lique M; Veening, Jan G; Wells, Adam B et al. (2003) Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: evidence for functional subdivisions. J Comp Neurol 463:132-56
Hayar, A; Heyward, P M; Heinbockel, T et al. (2001) Direct excitation of mitral cells via activation of alpha1-noradrenergic receptors in rat olfactory bulb slices. J Neurophysiol 86:2173-82
Ennis, M; Zhou, F M; Ciombor, K J et al. (2001) Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals. J Neurophysiol 86:2986-97
Griff, E R; Greer, C A; Margolis, F et al. (2000) Ultrastructural characteristics and conduction velocity of olfactory receptor neuron axons in the olfactory marker protein-null mouse. Brain Res 866:227-36
Ciombor, K J; Ennis, M; Shipley, M T (1999) Norepinephrine increases rat mitral cell excitatory responses to weak olfactory nerve input via alpha-1 receptors in vitro. Neuroscience 90:595-606
El-Etri, M M; Ennis, M; Griff, E R et al. (1999) Evidence for cholinergic regulation of basal norepinephrine release in the rat olfactory bulb. Neuroscience 93:611-7

Showing the most recent 10 out of 18 publications