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PRESYNAPTIC PLASTICITY OF VESICULAR DOPAMINE RELEASE

囊泡多巴胺释放的突触前可塑性

基本信息

批准号：
7596707
负责人：
David Sulzer
金额：
$ 14.02万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7596707
关键词：
Acridine Orange Acute Adderall Adrenal Glands Alkalinization Amphetamines Appendix Area Autoreceptors Back Basal Ganglia Behavior Caliber Catecholamines Cell membrane Cells Chromaffin Cells Chromaffin granule Chromosome Pairing Chronic Cocaine Collaborations Corpus striatum structure Cues Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cytoplasmic Granules Data Dense Core Vesicle Detection Dopamine Drug effect disorder Dyes Electric Capacitance Endocytosis Event Exocytosis Exposure to Flicker Fusion GDNF gene GDNF receptors Genetic Green Fluorescent Proteins Hippocampus (Brain)Incentives Incidence Individual Kinetics Knowledge Label Learning Letters Maintenance Measurement Measures Mediating Membrane Methods Methylphenidate Midbrain structure Molecular Conformation Mus Neurites Neurons Neurotransmitters Noise Numbers Optics Pathway interactions Phorbol 12,13-Dibutyrate Phorbol Esters Pituitary Gland Plastics Polymerase Chain Reaction Population Presynaptic Receptors Principal Investigator Probability Protein Isoforms Protein Kinase C Protein Overexpression Publishing Recording of previous events Regulation Reporting Resolution Ritalin Role Running Second Messenger Systems Secretory Vesicles Self Administration Signal Pathway Signal Transduction Site Solutions Staurosporine Stimulus Synapses Synaptic Vesicles Techniques Thinking Time Transgenic Mice Varicosity Vesicle Work axon growth base citrate carrier density dopamine transporter dopaminergic neuron effusion feeding foot kinase inhibitor mast cell millisecond mutant neurite growth presynaptic programs promoter protein kinase C-delta psychostimulant quantum receptor response second messenger selective attention size social synaptogenesis transmission process uptake

项目摘要

Presynaptic plasticity of dopamine release in the cortex and basal ganglia is involved in learning cues that elicit cocaine self-administration and underlie selective attention by filtering non-salient stimuli. The objective of this proposal is to characterize mechanisms that mediate presynaptic plasticity at the level of the dopaminergic synaptic vesicle exocytosis. We recently reported that the fusion pores of small DAergic synaptic vesicles can flicker once or multiple times as fast as 10 kHz, thus regulating the amount of transmitter released from a vesicle. This provides the basis for Aim 1, which asks how flickering of fusion pores is regulated. In chromaffin cells, we discovered that the level of vesicle acidification is not invariant but enhanced by cellular activity, which can increase quantal size. In this proposal, we show evidence for enhanced vesicular acidification that may underlie drug actions (e.g., Ritalin), and a means for behavior to feed back to alter long-term transmission. This provides the basis for Aim 2 explores whether psychostimulants regulate quantal size via rebound of vesicular acidification. Finally, we identified how a variety of presynaptic receptors alter DA transmission at the quantal level (e.g., GDNF, D2, nicotinic, and mGluR activation) and why these factors are important for DA as social synapses. Most of the work has been on acute effects of neurotransmitters. New evidence indicates long-lasting effects of neurotransmitters on DA transmission, particularly on the density/formation of axonal presynaptic varicosities. Accordingly, Aim 3 will examine how neurotransmitters regulate DAergic presynaptic varicosity formation.

皮层和基底神经节多巴胺释放的突触前可塑性与学习线索有关