The objective of this research is to understand how developing neurons form synapses onto particular neurons to form a functional neuronal circuit. These mechanisms will be studied in a relatively simple nervous system--that of the medicinal leech--because many of its neurons can be identified even before they start to grow the processes that will be the sites of synapses. In addition, a great deal is known about the morphological and physiological properties of these identifiable neurons, including the role that many of them play in generating behavior. Experiments will focus on the development of connections in two well-defined neural circuits: the connection between a pair of identified motor neurons, both of which innervate the same muscles in the body wall, and the connections in a reflex pathway that includes a sensory receptor, an effector neuron, and an intervening layer of a small number of interneurons. The generation of specificity will be approached using the following techniques: detailed morphological examinations of the spatial relationship between neuronal branches as the contacts are first established; physiological recordings from the synaptic connections as they form; and ablations of single neurons, of branches of neurons, or of peripheral targets, to perturb the environment in which the neurons are developing. These experiments will determine which mechanisms are operating in this well-defined system. For example, we will test whether neurons form synapses with any other neurons to which they are sufficiently close at a particular time; whether potential synaptic targets respond to environmental signals in a way that puts their branches in close proximity, even though the two neurons are behaving independently of one another; whether competition occurs for synaptic space between neurons that might be eligible to form synapses onto the same neuron; how the peripheral target of a neuron can control which synapses it will accept; and whether electrical activity is important for establishing or maintaining synaptic contacts. Experiments on other species, including higher mammals, have suggested that these same mechanisms control synaptic specificity in humans. The experimental tractability of the embryonic leech nervous system makes it possible to examine how the mechanisms interact to form a functional neuronal circuit among a number of identified neurons in a single species, thereby shedding light on how functional neuronal circuits are established in our own nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035336-06
Application #
6539883
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Chen, Daofen
Project Start
1997-01-01
Project End
2005-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
6
Fiscal Year
2002
Total Cost
$304,000
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Calzo, Jerel P; Corliss, Heather L; Blood, Emily A et al. (2013) Development of muscularity and weight concerns in heterosexual and sexual minority males. Health Psychol 32:42-51
Todd, Krista L; Kristan Jr, William B; French, Kathleen A (2010) Gap junction expression is required for normal chemical synapse formation. J Neurosci 30:15277-85
Baltzley, Michael J; Gaudry, Quentin; Kristan Jr, William B (2010) Species-specific behavioral patterns correlate with differences in synaptic connections between homologous mechanosensory neurons. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 196:181-97
Gaudry, Q; Ruiz, N; Huang, T et al. (2010) Behavioral choice across leech species: chacun a son gout. J Exp Biol 213:1356-65
Wagenaar, Daniel A; Gonzalez, Ruben; Ries, David C et al. (2010) Alpha-conotoxin ImI disrupts central control of swimming in the medicinal leech. Neurosci Lett 485:151-6
Gaudry, Quentin; Kristan Jr, William B (2010) Feeding-mediated distention inhibits swimming in the medicinal leech. J Neurosci 30:9753-61
Gaudry, Quentin; Kristan Jr, William B (2009) Behavioral choice by presynaptic inhibition of tactile sensory terminals. Nat Neurosci 12:1450-7
Marin-Burgin, Antonia; Kristan Jr, William B; French, Kathleen A (2008) From synapses to behavior: development of a sensory-motor circuit in the leech. Dev Neurobiol 68:779-87
Baca, Serapio M; Marin-Burgin, Antonia; Wagenaar, Daniel A et al. (2008) Widespread inhibition proportional to excitation controls the gain of a leech behavioral circuit. Neuron 57:276-89
Mesce, Karen A; Esch, Teresa; Kristan Jr, William B (2008) Cellular substrates of action selection: a cluster of higher-order descending neurons shapes body posture and locomotion. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 194:469-81

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