A long range objective of our studies is to understand how neurohormonal systems work. Our studies have concentrated on a lobster system involving the amines serotonin and octopamine, and the peptide proctolin. When serotonin and octopamine are injected into freely moving lobsters, they cause animals to assume sustained opposite postures: serotonin causes flexion and octopamine extension of the abdomen, claws and walking legs. the postures result from amines directing the readout of central motor programs for flexion (serotonin) and extension (octopamine). At the same time the amines and the peptide, proctolin, act on peripheral exoskeletal muscles to prime them to respond more vigorously. We have located the major sites of storage and release of these substances in lobsters and have found individual neurons likely to contain serotonin that may play a role in the generation of the postures. This application proposes to extend these studies by: first, using immunohistochemical methods, locating cells containing proctolin and octopamine (verified by chemical assays) then examining the neurohormone-containing cells to try to learn how they are activated, and the consequences of their activation on aspects of lobster behavior; second, examining further the mechanisms that underly the long-lasting nerohormone-induced actions on exoskeletal muscles by attempting to develop a skeletal muscle membrane preparation for detailed physiological anc biochemical studies, and also to continue studies with intact preparations on the possible involvement of cyclic nucleotides in these processes; third, in preliminary behavioral experiments we will explore the consequences of destroying amine neurons on aspects of lobster behavior. In a fourth set of experiments we will use lower vertebrane preparations to see if we can (1) identify unique amine-containing neurons and (2) develop methods for examining specific synaptic contacts in the spinal cord using quantitative physiological methods. Amine neuron systems in man have been implicated in disorders and diseases of the nervous system like Parkinson's Disease, depression and schizophrenia and in many important normal processes like sleep, attention, initiation of movement and learning. Our belief is that detailed knowledge of how an amine-associated system (like our lobster system) works, will generate useful ideas and experimental avenues of approach toward understanding the enigmatic and much more complicated amine-neuron systems of man and higher vertebrates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS007848-20
Application #
3393677
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1976-01-01
Project End
1990-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
20
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115