We propose to study the cellular and molecular basis of two implicit memory-dependent phenomena, repetition priming and task-switch cost. Our research is unusual in that it is conducted in a model system that is advantageous for characterizing underlying cellular/molecular mechanisms (i.e., we study a feeding network). Previously, we demonstrated that repetition priming of ingestion is mediated by modulatory peptides released from command-like neurons. These peptides exert second messenger-mediated effects and alter the excitability and firing frequency of neurons that determine response performance. In proposed experiments we will expand our biophysical analyses of modulator-induced currents. Our findings have generated considerable interest since modulatory peptides are likely to be involved in the induction of repetition priming in other systems and species. Other proposed experiments will study implications of repetition priming for task switching. One set of experiments will use a paradigm where one 'task'(ingestion) ends and another (egestion) begins shortly thereafter. Relatively rapid task switching is of interest since it is often accompanied by a cost, e.g., it is more likely that there will be an inappropriat response to stimulus presentation after the switch. We will test a model that postulates it is a consequence of persistent modulation, i.e., effects of modulators released during the priming of one task persist and negatively impact the performance of a subsequent task. This is an attractive hypothesis since it accounts for a common observation -costs associated with task switching are observed in systems that undergo repetition priming. Other experiments will study longer lasting consequences of task switching in the situation where a switch is followed by a return to the original task. Our preliminary data indicate that this paradigm reveals a previously unappreciated benefit of persistent modulation as a mechanism to configure a network. Namely, we suggest that it enables the retention of a primed state during task switching. To conclude, repetition priming and task cost switches are ubiquitous forms of implicit memory that are impaired under certain pathological conditions (e.g., ADHD patients show substantially larger switch costs than non-ADHD patients). Research such as ours, which will determine how repetition priming is mediated, may provide novel perspectives on these disorders.

Public Health Relevance

Repetition priming and task cost switches are manifestations of implicit memory that can be impaired under pathological conditions such as ADHD (Attention-Deficit/Hyperactivity Disorder) (e.g., Rauch et al., 2012). Despite the considerable general interest in repetition priming, it is not well understood at the cellular/molecular level. Studies such as ours will fill this major gap in current knowledge.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS066587-31
Application #
8756261
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Gnadt, James W
Project Start
Project End
Budget Start
Budget End
Support Year
31
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Cropper, Elizabeth C; Friedman, Allyson K; Jing, Jian et al. (2014) Neuromodulation as a mechanism for the induction of repetition priming. Curr Opin Neurobiol 29:33-8
Svensson, Erik; Proekt, Alex; Jing, Jian et al. (2014) PKC-mediated GABAergic enhancement of dopaminergic responses: implication for short-term potentiation at a dual-transmitter synapse. J Neurophysiol 112:22-9
Wu, Jin-Sheng; Wang, Nan; Siniscalchi, Michael J et al. (2014) Complementary interactions between command-like interneurons that function to activate and specify motor programs. J Neurosci 34:6510-21
Sasaki, Kosei; Sasaki, Kosai; Cropper, Elizabeth C et al. (2013) Functional differentiation of a population of electrically coupled heterogeneous elements in a microcircuit. J Neurosci 33:93-105
Dacks, Andrew M; Weiss, Klaudiusz R (2013) Release of a single neurotransmitter from an identified interneuron coherently affects motor output on multiple time scales. J Neurophysiol 109:2327-34
Dacks, Andrew M; Weiss, Klaudiusz R (2013) Latent modulation: a basis for non-disruptive promotion of two incompatible behaviors by a single network state. J Neurosci 33:3786-98
Jing, Jian; Sasaki, Kosei; Perkins, Matthew H et al. (2011) Coordination of distinct motor structures through remote axonal coupling of projection interneurons. J Neurosci 31:15438-49
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
Friedman, Allyson K; Weiss, Klaudiusz R (2010) Repetition priming of motoneuronal activity in a small motor network: intercellular and intracellular signaling. J Neurosci 30:8906-19
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

Showing the most recent 10 out of 13 publications