The long-term objectives of this proposal are to understand the neural bases for the changes in behavior that accompany changes in an animal's social status. Crayfish are an appropriate model because the differences in the behavior of dominant, subordinate and single (isolated) animals are well described, and the neural circuits that mediate relevant patterns of behavior, such as escape, have been well studied. The Lateral Giant (LG) interneuron in the escape circuit serves as a command neuron for the behavior. LG's excitability can be modulated by serotonin (5HT), but the sign of this modulation depends on the social status of the animal: 5HT facilitates LG's response in social dominant animals and inhibits it in social subordinates. The effect of serotonin in social isolates depends on the manner in which it is applied, whether fast or slow, at higher or lower concentrations, and for shorter or longer periods. These last effects, which are of clear clinical relevance, are hypothesized to result from activation of competing second messenger pathways through separate serotonin receptors, whereas the effects of social status may result from changes in the population of available receptors in the different animals. Accordingly, the first aim of the proposal is to describe the set of serotonin receptors that modulate LG's response by cloning, sequencing and expressing crayfish CNS serotonin receptors. Antibodies to those receptors will then reveal their location, and the discovery of selective agonists and antagonists will enable their different effects to be determined, cAMP mediates one effect of 5HT on LG; other 2nd messengers pathways will be identified and their interactions studied through the use of specific agonists and antagonists that can be either applied extracellularly or injected into the giant neuron. One effect of 5HT, long-term facilitation, is also produced by repeated bouts of sensory nerve stimulation; this pattern of stimulation is also known to evoke 5HT release. Another aim will be to determine whether release of 5HT mediates stimulus-induced long-term facilitation. Finally, the afferents to LG are electrically coupled;
the final aim will be to test whether this coupling forms a lateral excitatory network among the afferents to select and amplify phasic inputs to LG. This will be studied with standard electrophyiological techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS026457-13
Application #
6434628
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Edwards, Emmeline
Project Start
1988-07-01
Project End
2006-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
13
Fiscal Year
2002
Total Cost
$250,250
Indirect Cost
Name
Georgia State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
Antonsen, Brian L; Edwards, Donald H (2007) Mechanisms of serotonergic facilitation of a command neuron. J Neurophysiol 98:3494-504
Antonsen, Brian L; Herberholz, Jens; Edwards, Donald H (2005) The retrograde spread of synaptic potentials and recruitment of presynaptic inputs. J Neurosci 25:3086-94
Herberholz, Jens; Sen, Marjorie M; Edwards, Donald H (2004) Escape behavior and escape circuit activation in juvenile crayfish during prey-predator interactions. J Exp Biol 207:1855-63
Herberholz, Jens; Mims, Christopher J; Zhang, Xiaodong et al. (2004) Anatomy of a live invertebrate revealed by manganese-enhanced Magnetic Resonance Imaging. J Exp Biol 207:4543-50
Antonsen, Brian L; Edwards, Donald H (2003) Differential dye coupling reveals lateral giant escape circuit in crayfish. J Comp Neurol 466:1-13
Herberholz, Jens; Antonsen, Brian L; Edwards, Donald H (2002) A lateral excitatory network in the escape circuit of crayfish. J Neurosci 22:9078-85
Herberholz, J; Schmitz, B (2001) Signaling via water currents in behavioral interactions of snapping shrimp (Alpheus heterochaelis). Biol Bull 201:6-16
Heitler, W J; Edwards, D H (1998) Effect of temperature on a voltage-sensitive electrical synapse in crayfish. J Exp Biol 201:503-13
Yeh, S R; Musolf, B E; Edwards, D H (1997) Neuronal adaptations to changes in the social dominance status of crayfish. J Neurosci 17:697-708
Yeh, S R; Fricke, R A; Edwards, D H (1996) The effect of social experience on serotonergic modulation of the escape circuit of crayfish. Science 271:366-9

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