Neuronal networks are often multifunctional, that is, a single group of cells with anatomically defined synaptic connections can be reconfigured to produce different outputs. A major question that needs to be addressed is, how does this reconfiguration occur? Several studies have shown that circuit reconfiguration can be caused by extrinsic neuromodulatory inputs that alter neuronal properties and synaptic strengths. Alternatively, circuits can be self-reconfiguring, rearranging themselves based on their own activity pattern. Recent evidence suggests this may arise as a result of neuromodulatory actions of neurons intrinsic to the network. The purpose of this study is to examine the role of """"""""intrinsic neuromodulation"""""""" in circuit reconfiguration and rhythmic pattern generation. There is a network of neurons in the marine mollusc Tritonia that is capable of changing itself from a circuit that mediates a withdrawal reflex to one that produces a rhythmic escape swim behavior. Two cell types in the network evoke neuromodulatory effects on other cells in the circuit (one cell type is serotonergic, the other peptidergic). Since these cells are integral parts of the pattern generating circuit, they are activated during every swim episode. Thus, the circuit appears to modulate itself every time that it is activated and throughout its performance of the behavior.
The specific aims of this project are to I) identify the cellular and synaptic loci of intrinsic neuromodulation in the Tritonia swim circuit; II) determine the role of serotonin in producing some of these neuromodulatory effects; and Ill) study the role of intrinsic neuromodulation in circuit reconfiguration and pattern generation by adding the modulation to an existing computer simulation of the circuit. Studying this small neural network will provide more insights into the mechanisms of intrinsic neuromodulation, and will increase our understanding of the functional significance of this little-recognized form of nervous system plasticity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS035371-11S1
Application #
6558495
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Chen, Daofen
Project Start
1995-09-06
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
11
Fiscal Year
2002
Total Cost
$21,450
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
Hill, Evan S; Sakurai, Akira; Katz, Paul S (2008) Transient enhancement of spike-evoked calcium signaling by a serotonergic interneuron. J Neurophysiol 100:2919-28
Clemens, Stefan; Calin-Jageman, Robert; Sakurai, Akira et al. (2007) Altering cAMP levels within a central pattern generator modifies or disrupts rhythmic motor output. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 193:1265-71
Sakurai, Akira; Calin-Jageman, Robert J; Katz, Paul S (2007) Potentiation phase of spike timing-dependent neuromodulation by a serotonergic interneuron involves an increase in the fraction of transmitter release. J Neurophysiol 98:1975-87
Hill, Evan S; Katz, Paul S (2007) Role of membrane potential in calcium signaling during rhythmic bursting in tritonia swim interneurons. J Neurophysiol 97:2204-14
Sakurai, Akira; Darghouth, Naim R; Butera, Robert J et al. (2006) Serotonergic enhancement of a 4-AP-sensitive current mediates the synaptic depression phase of spike timing-dependent neuromodulation. J Neurosci 26:2010-21
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Katz, Paul S; Sakurai, Akira; Clemens, Stefan et al. (2004) Cycle period of a network oscillator is independent of membrane potential and spiking activity in individual central pattern generator neurons. J Neurophysiol 92:1904-17
Lynn-Bullock, Christina P; Welshhans, Kristy; Pallas, Sarah L et al. (2004) The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat 27:129-38
Clemens, Stefan; Katz, Paul S (2003) G protein signaling in a neuronal network is necessary for rhythmic motor pattern production. J Neurophysiol 89:762-72
Sakurai, Akira; Katz, Paul S (2003) Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit. J Neurosci 23:10745-55

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