title: Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca²⁺ channels, calmodulin and myosin light-chain kinase.
abstract: Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer's disease, schizophrenia and Parkinson's disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats. Our results demonstrate that NT persistently increased the amplitude of the AMPA receptor-mediated EPSCs at the PP-GC synapse. NT-induced increases in AMPA EPSCs were mediated by presynaptic NTS1 receptors. NT reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that NT facilitates presynaptic glutamate release. NT increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. NT-mediated augmentation of glutamate release required the influx of Ca(2+) via L-type Ca(2+) channels and the functions of calmodulin and myosin light chain kinase. Our results provide a cellular and molecular mechanism to explain the roles of NT in the hippocampus.
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA; Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
authors.forename: Haopeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA. Electronic address: saobo.lei@med.und.edu.
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D018345:Mice, Knockout; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000008:administration & dosage / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D018028:Receptors, Neurotensin; D009496:Neurotensin; D018698:Glutamic Acid; D009219:Myosin-Light-Chain Kinase; D002118:Calcium
keywords: Alzheimer's disease; Ca(2+); Ca(2+) channels; G proteins; Hippocampus; Myosin light chain kinase; Synapse; Synaptic transmission; glutamate
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