Although it is well established that the speed of many complex behaviors is subject to priming, i. e. facilitation by previous responses, and once primed the increased response speed can persist for a considerable period of time, there is a dearth of information about the neuronal mechanisms that are responsible for the development of priming or for the memory component of the primed state. The long range goal of the research presented in this proposal is to understand the neural mechanisms that lead to the progressive increase of the speed of responding and of the mechanisms that are responsible for the memory component of this process, i.e. its persistence. We propose to use the well characterized feeding behavior and its neural substrate in Aplysia in order to extract the principles which relate the properties of the stimuli, synaptic plasticity and plasticity of the biophysical characteristics of behavior generating neurons to the process of the development and memory of the primed state. We propose to test a hypothesis that the development and memory of the primed state are a result of a series of steps that include: a) suppression of antagonistic responses, b) short term synaptic facilitation, and c) modulation of the biophysical characteristics of neurons by peptidergic co-transmitters that are released from the neurons that participate in the generation of the behavior. The proposed projects include: 1) characterization of synaptic plasticity of interneurons that facilitate antagonistic behaviors; 2) identification of cellular correlates of the development and of the memory of the primed state; 3) identification of transmitters and modulators contained in neurons that are involved in the development and memory of the primed state, 4) determination of the cellular mechanisms of action of these modulators and their contribution to the development and memory of priming. The research will utilize an interdisciplinary approach in which classical electrophysiological approaches are combined with cell biological, molecular and biochemical techniques to critically test the proposed hypotheses. The general importance of this type of research is likely to extend beyond the specific findings that we will obtain, as the mechanisms that are responsible for response selection, response priming, and the short term memory of these processes are likely to participate in a multitude of behaviors that for their efficiency rely on short term memory and selective attention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA013330-01
Application #
6041953
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Volman, Susan
Project Start
2000-02-01
Project End
2005-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
1
Fiscal Year
2000
Total Cost
$325,514
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Jing, Jian; Sweedler, Jonathan V; Cropper, Elizabeth C et al. (2010) Feedforward compensation mediated by the central and peripheral actions of a single neuropeptide discovered using representational difference analysis. J Neurosci 30:16545-58
Vilim, Ferdinand S; Sasaki, Kosei; Rybak, Jurgen et al. (2010) Distinct mechanisms produce functionally complementary actions of neuropeptides that are structurally related but derived from different precursors. J Neurosci 30:131-47
Wu, Jin-Sheng; Vilim, Ferdinand S; Hatcher, Nathan G et al. (2010) Composite modulatory feedforward loop contributes to the establishment of a network state. J Neurophysiol 103:2174-84
Jing, Jian; Vilim, Ferdinand S; Cropper, Elizabeth C et al. (2008) Neural analog of arousal: persistent conditional activation of a feeding modulator by serotonergic initiators of locomotion. J Neurosci 28:12349-61
Jing, Jian; Vilim, Ferdinand S; Horn, Charles C et al. (2007) From hunger to satiety: reconfiguration of a feeding network by Aplysia neuropeptide Y. J Neurosci 27:3490-502
Proekt, Alex; Vilim, Ferdinand S; Alexeeva, Vera et al. (2005) Identification of a new neuropeptide precursor reveals a novel source of extrinsic modulation in the feeding system of Aplysia. J Neurosci 25:9637-48
Furukawa, Y; Nakamaru, K; Sasaki, K et al. (2003) PRQFVamide, a novel pentapeptide identified from the CNS and gut of Aplysia. J Neurophysiol 89:3114-27
Jing, Jian; Vilim, Ferdinand S; Wu, Jin-Sheng et al. (2003) Concerted GABAergic actions of Aplysia feeding interneurons in motor program specification. J Neurosci 23:5283-94
Morgan, Peter T; Jing, Jian; Vilim, Ferdinand S et al. (2002) Interneuronal and peptidergic control of motor pattern switching in Aplysia. J Neurophysiol 87:49-61
Sweedler, J V; Li, L; Rubakhin, S S et al. (2002) Identification and characterization of the feeding circuit-activating peptides, a novel neuropeptide family of aplysia. J Neurosci 22:7797-808

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