TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN

PVCN 中胆碱能标记物的瞬时表达

• 批准号: 7585844
• 负责人: Barbara J Morley
• 金额: $ 13.23万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-06 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7585844
• 关键词: ARHGEF5 gene; Acetylcholine; Acetylcholinesterase; Adult; Affect; Affinity; Age; Agonist; Auditory; Auditory system; Axon; Behavior; Biochemical; Brain; Bungarotoxins; Calcium; Carrier Proteins; Cells; Child; Choline; Choline O-Acetyltransferase; Cholinergic Agents; Cholinergic Receptors; Chromosome Pairing; Cochlear nucleus; Data; Development; Diffuse; Environment; Enzymes; Event; Extracellular Space; Gene Expression; Glutamate Receptor; Glutamates; Goals; Hearing; Histocytochemistry; Image; In Situ Hybridization; Laboratories; Language Disorders; Light; Link; Literature; Localized; Long-Term Effects; Measures; Methods; Microscopic; Minor; Molecular; Mothers; Mutant Strains Mice; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nerve; Nerve Tissue; Neurons; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Nicotinic Receptors; Octopus; Pathway interactions; Presynaptic Terminals; Proteins; Purpose; Rattus; Receptor Gene; Regulation; Research Personnel; Rodent; Role; Series; Site; Slice; Smoke; Synapses; System; Testing; Toxin; Vertebral column; Vesicle; Vesicular Transport Proteins; Week; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; amino 3 hydroxy 5 methylisoxazole 4 propionate; base; cholinergic; cholinergic neuron; day; deafness; experience; fetal; mRNA Expression; methyllycaconitine; nanoGold; neurochemistry; neuronal cell body; neurotransmission; novel; postnatal; postsynaptic; presynaptic; programs; pup; receptor binding; receptor expression; synaptic function; synaptogenesis; uptake

The pathways and synaptic connections in the brain are established by a finely orchestrated series of neurochemical events. Although central auditory system synapses are modified by experience after the onset of hearing, synaptic connectivity is established before the eighth nerve is responsive to the external environment. There is an emerging literature indicating that some enzymes and proteins with minor roles in neurotransmission in the adult brain have major roles in guiding axons and establishing synapses during development. Acetylcholine (ACh), acetylcholinesterase (AChE) and the a7 nicotinic acetylcholine receptor (nAChR) are among the neurochemicals that regulate synaptic events, including the expression of genes obligatory for mature synapse formation in target neurons. In our laboratory, we have discovered a pathway projecting to the rodent octopus cell region of the posterior ventral cochlear nucleus (PVCN) that transiently expresses AChE and the a? nAChR during the second postnatal week. Ultrastructural studies indicate that few synaptic junctions are present by postnatal day 3, and are abundant by P5. The temporal sequence of the expression of the cholinergic markers, together with electrophysiological data from other laboratories, suggests that ACh and related enzymes and proteins are essential for the maturation of synapses. One of their functions may be to modulate glutamatergic receptor gene expression. Toxins that specifically affect cholinergic receptors, such as nicotine, concentrate in the fetal and postnatal brain in physiologically relevant concentrations. While this would not cause deafness, it could contribute to long-term language deficits. The goal of the proposed studies is to elucidate the cholinergic molecular mechanisms related to the maturation of synapses and regulation of NMDA receptor gene expression in the rodent PVCN. The overall hypothesis is that the diffuse release of ACh regulates NMDA glutamate receptor expression by regulating intracellular calcium through a? nicotinic acetylcholine receptors clustered on postsynaptic sites of PVCN octopus cells. The specific hypotheses are: (1) ACh release is nonvesicular; (2) nAChRs are clustered postsynaptically on octopus cells; ACh (3) a? nAChRs on octopus cells regulate intracellular calcium before, but not after, the onset of hearing; (4) nicotine administration will upregulate NMDA, but not AMPA, receptor gene expression; and (5) ACh, through a7 nAChRs, regulates NMDA glutamate receptor expression.

大脑中的通路和突触连接是由一系列精心安排的