Priming is a class of ubiquitous behavioral phenomena defined as progressive increase in the speed and strength of behavioral responses to repeated stimuli. Priming has a clear mnemonic component, i.e., responses remain potentiated for a considerable period of time. Thus priming is a simple form of memory. The long-range goal of our research is to determine how priming is initially established, and how it is maintained. Our studies will be conducted in a well-characterized circuit, which generates biting behavior. Experimental advantages of our system include its simplicity, extensive information on the synaptic organization, neurotransmitters and neuromodulators that are present in key circuit elements. Our preliminary data leads us to propose the following hypothesis: Priming is a system-level phenomenon that arises as a result of the interaction between two competing processes, those that actively suppress responses and those that facilitate them. We propose that responses to the initial presentation of the stimulus are actively suppressed. As the stimulus is repeatedly presented, these response-suppressing processes weaken or are surmounted by the response-facilitating processes, ultimately giving rise to the progressive strengthening and speeding-up of the responses. Our preliminary data implicate several neuropeptides act as mediators of these progressive changes in both the response-facilitating and response-suppressing processes. Slow time course of effects of these neuropeptides implicates them in the maintenance of the primed state. We propose to test this model in a series of interdisciplinary experiments that include electrophysiological, biochemical, molecular, and morphological techniques. The general importance of this type of research is likely to extend beyond the specific findings that we obtain because the general mechanisms that underlie motor priming are likely to operate in other contexts. Pathologies in priming mechanisms may be involved in attention disorders, learning disabilities and drug addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA013330-09
Application #
7393228
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Volman, Susan
Project Start
2000-02-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
9
Fiscal Year
2008
Total Cost
$275,629
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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; 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
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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