The brain processes information and generates behavior by transmitting signals at its synapses, which connect neurons into vast networks of communicating cells. These networks, known as neural circuits, are not static but are modified throughout life by experience. Such neural circuit plasticity is critical for the brain to develop normally and perform all of its important functions, including learning and memory. When brain plasticity mechanisms function abnormally, however, devastating mental illnesses often ensue. Thus, a major goal of neuroscience research is to understand the detailed mechanisms by which the brain activity generated by experiences modifies neural circuit behavior. This occurs in large part because neural activity continually adjusts the efficiency or strength of synaptic communication between neurons, a process known as synaptic plasticity. Despite the importance of synaptic plasticity for brain development and higher brain functions, relatively little is known about its molecular mechanisms other than it is commonly triggered by activity-dependent changes in intracellular calcium levels. This Conte Center will bring together four leading investigators who will use an innovative molecular screening approach combined with sophisticated biochemical, electrophysiological, and imaging assays to elucidate novel intracellular signaling pathways that underlie different forms of synaptic plasticity and how these forms of synaptic plasticity modify circuit function. The new Insights into synaptic plasticity mechanisms generated by this Conte Center will influence a broad array of neuroscientists working on a wide range of topics related to normal and pathological brain function. The Conte Center will also provide the research community with novel genetic tools that can be used to manipulate intracellular signaling pathways throughout the brain as well as novel transgenic mouse models that can be used to explore the roles of different signaling pathways and forms of synaptic plasticity in normal and pathological behaviors. Thus the Conte Center will provide both technological and intellectual innovations to one of the most important areas of neuroscience research with far ranging implications for our understanding of normal and diseased brain function.

Public Health Relevance

The effectiveness of communication between nerve cells is modified by experience and these modifications are crucial for all normal brain functions including learning and memory. The goal of this project is to determine the molecular mechanisms that are responsible for these modifications. Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086403-05
Application #
8529617
Study Section
Special Emphasis Panel (ZMH1-ERB-C (05))
Program Officer
Asanuma, Chiiko
Project Start
2009-09-30
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$1,661,874
Indirect Cost
$536,863
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Berndt, Andre; Lee, Soo Yeun; Wietek, Jonas et al. (2016) Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity. Proc Natl Acad Sci U S A 113:822-9
Jiang, M; Polepalli, J; Chen, L Y et al. (2016) Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell-autonomous NMDA receptor-independent mechanism. Mol Psychiatry :
Martinelli, David C; Chew, Kylie S; Rohlmann, Astrid et al. (2016) Expression of C1ql3 in Discrete Neuronal Populations Controls Efferent Synapse Numbers and Diverse Behaviors. Neuron 91:1034-51
Zhang, Bo; Chen, Lulu Y; Liu, Xinran et al. (2015) Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses. Neuron 87:781-96
Kim, Jae-Ick; Ganesan, Subhashree; Luo, Sarah X et al. (2015) Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons. Science 350:102-6
Steinberg, Elizabeth E; Christoffel, Daniel J; Deisseroth, Karl et al. (2015) Illuminating circuitry relevant to psychiatric disorders with optogenetics. Curr Opin Neurobiol 30:9-16
Yang, Xiaofei; Pei, Jimin; Kaeser-Woo, Yea Jin et al. (2015) Evolutionary conservation of complexins: from choanoflagellates to mice. EMBO Rep 16:1308-17
Arendt, Kristin L; Zhang, Zhenjie; Ganesan, Subhashree et al. (2015) Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis. Proc Natl Acad Sci U S A 112:E5744-52
Acuna, Claudio; Liu, Xinran; Gonzalez, Aneysis et al. (2015) RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release. Neuron 87:1234-47
Fuccillo, Marc V; Földy, Csaba; Gökce, Özgün et al. (2015) Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms. Neuron 87:326-40

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