The hippocampal mossy fiber system has been proposed by many to be an ideal system for analyses of the function of opioid peptides. This anatomically well defined (and electrophysiologically accessible) axonal system has been found, by the applicant and others, to contain enkephalin (ENK)-, dynorphin (DYN)- and (in guinea pig and mouse) cholecystokinin (CCK)-like immunoreactivity. It is not known whether these peptides are colocalized or are present in distinct mossy fiber populations. There is evidence that mossy fiber ENK and, less certainly, DYN and CCK content is altered by seizure activity and a range of studies indirectly suggest that these peptides are involved in the regulation of epileptiform activity as well. It is the goal of the proposed research to further refine our understanding of the fine localization of ENK-, DYN-, and CCK-like immunoreactivities in the mossy fiber system through the application of immunoelectron microscopic techniques and to evaluate the recipricol interaction of these mossy fiber peptides with epileptiform activity. Specifically the latter studies propose to: 1) quantify the influence of seizure activity on DYN, ENK, and CCK immunoreactivities in hippocampus by radioimmunoassay; 2) evaluate the impact of the seizure-induced increase in mossy fiber terminal-contained ENK (and possibly DYN) immunoreactivity on opiate receptor binding patterns; and 3) use the in vitro hippocampal slice preparation and a penicillin-induced interictal-spike paradigm to evaluate the (positive or negative) epileptogenic effects of mossy fiber-contained peptides. The anatomical (EM and autoradiographic) studies should help clarify unresolved issues as to the 'place' of ENK, DYN, and CCK in hippocampal circuitry and thereby limit the range of considerations as to the local physiological role of these substances. It is hoped that data from the proposed studies will combine to advance our understanding of the involvement of hippocampal peptides in limbic seizure activity and, more generally, the interaction between physiological activity, terminal-contained peptide concentration, and peptide receptors throughout the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
5K04NS000915-05
Application #
3074784
Study Section
Neurology A Study Section (NEUA)
Project Start
1984-12-01
Project End
1989-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Gall, C; Murray, K; Isackson, P J (1991) Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus. Brain Res Mol Brain Res 9:113-23
Perlmutter, L S; Gall, C; Baudry, M et al. (1990) Distribution of calcium-activated protease calpain in the rat brain. J Comp Neurol 296:269-76
Gall, C M; Isackson, P J (1989) Limbic seizures increase neuronal production of messenger RNA for nerve growth factor. Science 245:758-61
Baudry, M; Shahi, K; Gall, C (1988) Induction of ornithine decarboxylase in adult rat hippocampal slices. Brain Res 464:313-8
Perlmutter, L S; Siman, R; Gall, C et al. (1988) The ultrastructural localization of calcium-activated protease ""calpain"" in rat brain. Synapse 2:79-88
Gall, C M; Pico, R M; Lauterborn, J C (1988) Focal hippocampal lesions induce seizures and long-lasting changes in mossy fiber enkephalin and CCK immunoreactivity. Peptides 9 Suppl 1:79-84
Gall, C (1988) Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. J Neurosci 8:1852-62
Gall, C M; Hendry, S H; Seroogy, K B et al. (1987) Evidence for coexistence of GABA and dopamine in neurons of the rat olfactory bulb. J Comp Neurol 266:307-18
Hunt, C A; Seroogy, K B; Gall, C M et al. (1987) Cholecystokinin innervation of rat thalamus, including fibers to ventroposterolateral nucleus from dorsal column nuclei. Brain Res 426:257-69
White, J D; Gall, C M; McKelvy, J F (1987) Enkephalin biosynthesis and enkephalin gene expression are increased in hippocampal mossy fibers following a unilateral lesion of the hilus. J Neurosci 7:753-9

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