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Mtor and interneuron

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https://www.readbyqxmd.com/read/27764673/presynaptic-protein-synthesis-is-required-for-long-term-plasticity-of-gaba-release
#1
Thomas J Younts, Hannah R Monday, Barna Dudok, Matthew E Klein, Bryen A Jordan, István Katona, Pablo E Castillo
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons...
October 19, 2016: Neuron
https://www.readbyqxmd.com/read/27405707/receptor-tyrosine-kinase-epha7-is-required-for-interneuron-connectivity-at-specific-subcellular-compartments-of-granule-cells
#2
Simone Beuter, Ziv Ardi, Omer Horovitz, Jennifer Wuchter, Stefanie Keller, Rinki Saha, Kuldeep Tripathi, Rachel Anunu, Orli Kehat, Martin Kriebel, Gal Richter-Levin, Hansjürgen Volkmer
Neuronal transmission is regulated by the local circuitry which is composed of principal neurons targeted at different subcellular compartments by a variety of interneurons. However, mechanisms that contribute to the subcellular localisation and maintenance of GABAergic interneuron terminals are poorly understood. Stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin and its interaction with the guanine nucleotide exchange factor collybistin. Lentiviral knockdown experiments in adult rats indicated that the receptor tyrosine kinase EphA7 is required for the stabilisation of basket cell terminals on proximal dendritic and somatic compartments of granular cells of the dentate gyrus...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27018320/differential-effects-of-rapamycin-treatment-on-tonic-and-phasic-gabaergic-inhibition-in-dentate-granule-cells-after-focal-brain-injury-in-mice
#3
Corwin R Butler, Jeffery A Boychuk, Bret N Smith
The cascade of events leading to post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) remains unclear. Altered inhibition in the hippocampal formation and dentate gyrus is a hallmark of several neurological disorders, including TBI and PTE. Inhibitory synaptic signaling in the hippocampus is predominately driven by γ-aminobutyric acid (GABA) neurotransmission, and is prominently mediated by postsynaptic type A GABA receptors (GABAAR's). Subsets of these receptors involved in tonic inhibition of neuronal membranes serve a fundamental role in maintenance of inhibitory state, and GABAAR-mediated tonic inhibition is altered functionally in animal models of both TBI and epilepsy...
June 2016: Experimental Neurology
https://www.readbyqxmd.com/read/26066070/antidepressant-drug-action-from-rapid-changes-on-network-function-to-network-rewiring
#4
REVIEW
Tomi Rantamäki, Ipek Yalcin
There has been significant recent progress in understanding the neurobiological mechanisms of antidepressant treatments. The delayed-onset of action of monoamine-based antidepressant drugs have been associated to their ability to slowly increase synaptic plasticity and neuronal excitability via altering neurotrophic signaling (synthesis of BDNF and activation of its receptor TrkB), dematuration of GABAergic interneurons and inhibition of "breaks of plasticity". On the other hand, antidepressants rapidly regulate emotional processing that - with the help of heightened plasticity and appropriate rehabilitation - gradually lead to significant changes on functional neuronal connectivity and clinical recovery...
January 4, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/26044973/5-ht6-receptor-antagonists-potential-efficacy-for-the-treatment-of-cognitive-impairment-in-schizophrenia
#5
REVIEW
Natasja M W J de Bruin, Chris G Kruse
5-hydroxytryptamine6 receptor (5-HT6R) antagonists have shown efficacy in animal models for cognitive impairment in multiple cognitive domains relevant for schizophrenia. Improvements were found with 5-HT6R antagonists in preclinical tests for episodic memory, social cognition, executive function, working memory and several other tests for both learning and memory. In contrast, there is little evidence for efficacy on attention. It will be interesting to further investigate 5-HT6R antagonists in neurodevelopmental animal models which are based on prenatal exposure to specific environmental insults, and are characterized by a high level of face, construct and predictive validity for cognitive impairments associated with schizophrenia...
2015: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/23964198/thyroid-hormone-dependent-development-of-early-cortical-networks-temporal-specificity-and-the-contribution-of-trkb-and-mtor-pathways
#6
Sören Westerholz, Ana D de Lima, Thomas Voigt
Early in neocortical network development, triiodothyronine (T3) promotes GABAergic neurons' population increase, their somatic growth and the formation of GABAergic synapses. In the presence of T3, GABAergic interneurons form longer axons and conspicuous axonal arborizations, with an increased number of putative synaptic boutons. Here we show that the increased GABAergic axonal growth is positively correlated with the proximity to non-GABAergic neurons (non-GABA). A differential innervation emerges from a T3-dependent decrease of axonal length in fields with low density of neuronal cell bodies, combined with an increased bouton formation in fields with high density of neuronal somata...
2013: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/21883182/rapamycin-suppresses-axon-sprouting-by-somatostatin-interneurons-in-a-mouse-model-of-temporal-lobe-epilepsy
#7
Paul S Buckmaster, Xiling Wen
PURPOSE: In temporal lobe epilepsy many somatostatin interneurons in the dentate gyrus die. However, some survive and sprout axon collaterals that form new synapses with granule cells. The functional consequences of γ-aminobutyric acid (GABA)ergic synaptic reorganization are unclear. Development of new methods to suppress epilepsy-related interneuron axon sprouting might be useful experimentally. METHODS: Status epilepticus was induced by systemic pilocarpine treatment in green fluorescent protein (GFP)-expressing inhibitory nerurons (GIN) mice in which a subset of somatostatin interneurons expresses GFP...
November 2011: Epilepsia
https://www.readbyqxmd.com/read/20358377/epilepsy-secondary-to-tuberous-sclerosis-lessons-learned-and-current-challenges
#8
REVIEW
Romina Moavero, Caterina Cerminara, Paolo Curatolo
BACKGROUND: In tuberous sclerosis complex (TSC), a substantially increased risk of developing epilepsy is present as a result of a disruption of a TSC gene expression in the brain and secondary abnormal cellular differentiation, migration, and proliferation. Dysregulated excitation probably has its roots in the disruption of GABAergic interneuron development. There is an age-dependent electroclinical expression of seizures, and epilepsy is often quite severe and unremitting. DISCUSSION: The majority of patients (>60%) who are candidates for surgery remain seizure-free after tuberectomy...
November 2010: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/19648913/cannabinoid-modulation-of-hippocampal-long-term-memory-is-mediated-by-mtor-signaling
#9
Emma Puighermanal, Giovanni Marsicano, Arnau Busquets-Garcia, Beat Lutz, Rafael Maldonado, Andrés Ozaita
Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis...
September 2009: Nature Neuroscience
https://www.readbyqxmd.com/read/16183639/glutamatergic-regulation-of-the-p70s6-kinase-in-primary-mouse-neurons
#10
Guido Lenz, Joseph Avruch
Brief glutamatergic stimulation of neurons from fetal mice, cultured in vitro for 6 days, activates the mTOR-S6 kinase, ERK1/2 and Akt pathways, to an extent approaching that elicited by brain-derived neurotrophic factor. In contrast, sustained glutamatergic stimulation inhibits ERK, Akt, and S6K. Glutamatergic activation of S6K is calcium/calmodulin-dependent and is prevented by inhibitors of calcium/calmodulin-dependent protein kinase 2, phosphatidylinositol 3-OH-kinase and by rapamycin. 2-Amino-5-phosphonovaleric acid, an inhibitor of N'-methyl-D-aspartate receptors, abolishes glutamatergic activation of ERK1/2 but not the activation of mTOR-S6K; the latter is completely abolished by inhibitors of voltage-dependent calcium channels...
November 18, 2005: Journal of Biological Chemistry
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