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 Ca2+ via L-type Ca2+ 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.

Impaired chromaffin cell excitability and exocytosis in autistic Timothy syndrome TS2‐neo mouse rescued by L‐type calcium channel blockers

“…; Zhang et al . ). Compelling evidence suggests that synaptic neurotransmission shares common molecular elements with the secretory apparatus of CCs (Jahn & Fasshauer, ; Neher, ).…”

“…The altered neurotransmitter release induced by TS2-mutated Cav1.2 channels suggests the intriguing possibility that similar changes could occur on brain synapses. Cav1.2 and Cav1.3 do not contribute to the synchronous neurotransmitter release in central synapses (Simms & Zamponi, 2014;Zamponi, 2016) but regulate the Ca 2+ required for vesicle replenishment (Okita et al 2000;Fourcaudot et al 2009;Zorrilla de San Martin et al 2010;Zhang et al 2015). Compelling evidence suggests that synaptic neurotransmission shares common molecular elements with the secretory apparatus of CCs (Jahn & Fasshauer, 2012;Neher, 2018).…”

Diverse actions of the modulatory peptide neurotensin on central synaptic transmission

“…Neurotensin also modulates the presynaptic release of glutamate and catecholamines. In the dentate gyrus, NT induces long‐term potentiation of glutamate neurotransmission by increasing release probability and the number of readily releasable glutamate vesicles (Zhang et al ., ). This long‐term potentiation proceeds via activation of NTS1 resulting in influx of Ca 2+ through L‐type Ca 2+ channels and requires activation of calmodulin and myosin light‐chain kinase (Zhang et al ., ).…”

“…In the dentate gyrus, NT induces long‐term potentiation of glutamate neurotransmission by increasing release probability and the number of readily releasable glutamate vesicles (Zhang et al ., ). This long‐term potentiation proceeds via activation of NTS1 resulting in influx of Ca 2+ through L‐type Ca 2+ channels and requires activation of calmodulin and myosin light‐chain kinase (Zhang et al ., ). In the parabrachial nucleus, NT increases the amplitude of evoked and spontaneous AMPA receptor‐mediated EPSCs without altering currents elicited by bath application of AMPA, suggesting a presynaptic enhancement of glutamate release (Saleh et al ., ).…”

Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review

“…Currently, 22 amino acids (50–71), namely phenylalanine (50), leucine (51), isoleucine (52), tryptophan (53), γ-aminobutyric acid (54), methionine (55), valine (56), proline (57), tyrosine (58), alanine (59), hydroxyproline (60), threonine (61), glycine (62), glutamate (63), glutamine (64), lysine (65), serine (66), asparagine (67), aspartic acid (68), citrulline (69), arginine (70), and ornithine (71), have been obtained from the flowers, roots, stems, and leaves of A. manihot ( Du L. et al., 2015 ; Liu et al., 2016 ). Furthermore, it is recognized that amino acids from A. manihot contribute to the regulation of whole-body metabolism and play a key role in neurotransmission and lipid transport, as well as being involved in many pharmacological activities ( Wang et al., 2010 ; Zhou et al., 2013 ; Refaey et al., 2015 ; Zhang et al., 2015 ).…”