scholarly journals An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Silke Frahm ◽  
Beatriz Antolin-Fontes ◽  
Andreas Görlich ◽  
Johannes-Friedrich Zander ◽  
Gudrun Ahnert-Hilger ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Critical Role ◽  
Conditioned Reward ◽  
Quantal Size ◽  
Medial Habenula ◽  
Vesicular Transporters ◽  
Circuit Function ◽  
And Behavior ◽  
Presynaptic Facilitation

A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior.

scholarly journals Co-localization of different Neurotransmitter Transporters on the same Synaptic Vesicle is Bona-fide yet Sparse

2021 ◽  
Author(s):  
Neha Upmanyu ◽  
Jialin Jin ◽  
Marcelo Ganzella ◽  
Leon Boesche ◽  
Viveka Nand Malviya ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Glutamate Uptake ◽  
Quantitative Imaging ◽  
Small Population ◽  
Mammalian Brain ◽  
Content Type ◽  
Quantal Size ◽  
Vesicle Pools ◽  
Bona Fide ◽  
Vesicular Transporters

Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain neurons in mammalian brain release multiple transmitters, the prevalence, physiology of such pluralism and if the release occurs from same or distinct vesicle pools is not clear. Using quantitative imaging and biochemical approaches, we show that only a small population of neuronal SVs contain different VTs to accomplish corelease. Surprisingly, a highly diverse SV population (27 types) exist that express dual transporters suggesting corelease of diverse combinations of dual neurotransmitters, which includes the vesicle type that contains glutamate and zinc accounting for ∼34% of all SVs. Importantly, we demonstrate that transporter colocalization influences vesicular glutamate uptake leading to enhanced synaptic quantal size. Thus, localization of diverse transporters on single vesicles is bona-fide and the mechanism may underlie regulation of transmitter content, type and release in space and time.

Synthesis, Packaging, and Termination of Neurotransmitters

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Molecular Weight ◽  
Synaptic Vesicles ◽  
Drugs Of Abuse ◽  
Low Molecular Weight ◽  
Stiff Person Syndrome ◽  
Catecholamine Synthesis ◽  
Vesicular Transporters ◽  
Psychotropic Effects ◽  
Gaba Synthesis

The synthesis, packaging, and termination of action of neurotransmitters are detailed. There are far more varieties of peptide neurotransmitters than there are of low-molecular-weight neurotransmitters. Yet low-molecular-weight neurotransmitters are the ubiquitous workhorses of the nervous system. Acetylcholine, the catecholamines norepinephrine and dopamine, serotonin, glutamate, and GABA are examined in some depth. The vesicular transporters that carry low-molecular-weight neurotransmitters from the cytoplasm into synaptic vesicles are covered. The role of monoamines in affect and mood and the psychotropic effects of monoaminergic drugs are discussed. Principles of catecholamine synthesis are applied to understand phenylketonuria. Uptake of monoamines into neurons is discussed in the context of amphetamine, cocaine, and other drugs of abuse. Stiff-person syndrome, which results from an impairment of GABA synthesis, is introduced. The modes of action for peptide and gaseous neurotransmitters are briefly covered.

Psychology as a Historical Science

2021 ◽  
Vol 72 (1) ◽  
pp. 717-749
Author(s):  
Michael Muthukrishna ◽  
Joseph Henrich ◽  
Edward Slingerland
Keyword(s):  
Critical Role ◽  
Cross Cultural ◽  
Human Cognition ◽  
Cultural Variation ◽  
Historical Science ◽  
Historical Texts ◽  
Subject Pool ◽  
Work Psychology ◽  
And Behavior

Psychology has traditionally seen itself as the science of universal human cognition, but it has only recently begun seriously grappling with cross-cultural variation. Here we argue that the roots of cross-cultural variation often lie in the past. Therefore, to understand not only how but also why psychology varies, we need to grapple with cross-temporal variation. The traces of past human cognition accessible through historical texts and artifacts can serve as a valuable, and almost completely unutilized, source of psychological data. These data from dead minds open up an untapped and highly diverse subject pool. We review examples of research that may be classified as historical psychology, introduce sources of historical data and methods for analyzing them, explain the critical role of theory, and discuss how psychologists can add historical depth and nuance to their work. Psychology needs to become a historical science if it wants to be a genuinely universal science of human cognition and behavior.

scholarly journals Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice

2018 ◽  
Vol 115 (51) ◽  
pp. 13105-13110 ◽  
Author(s):  
Hongsheng Wang ◽  
Fang Liu ◽  
Wenbing Chen ◽  
Xiangdong Sun ◽  
Wanpeng Cui ◽  
...  
Keyword(s):  
Neural Development ◽  
Critical Role ◽  
Gaba Release ◽  
Brain Disorders ◽  
Gabaergic Transmission ◽  
Brain Functions ◽  
Adult Mice ◽  
Mutant Strains ◽  
And Behavior

Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1–ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively. We found that ErbB4 deletion in adult mice impaired behavior and GABA release but had no effect on neuron numbers and morphology. On the other hand, some deficits due to the ErbB4 null mutation during development were alleviated by restoring ErbB4 expression at the adult stage. Together, our results indicate a critical role of NRG1–ErbB4 signaling in GABAergic transmission and behavior in adulthood and suggest that restoring NRG1–ErbB4 signaling at the postdevelopmental stage might benefit relevant brain disorders.

scholarly journals Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

2021 ◽  
Author(s):  
Tania Lopez-Hernandez ◽  
Koh-ichiro Takenaka ◽  
Yasunori Mori ◽  
Pornparn Kongpracha ◽  
Shushi Nagamori ◽  
...  
Keyword(s):  
Cell Surface ◽  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Physiological Temperature ◽  
The Reformation ◽  
Comprehensive Survey ◽  
Vesicular Transporters ◽  
Clathrin Adaptor ◽  
Central Synapses

Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Conflicting models have been proposed regarding the mechanisms of SV endocytosis, most notably clathrin/ AP-2-mediated endocytosis and clathrin-independent ultrafast endocytosis. Partitioning between these pathways has been suggested to be controlled by temperature and stimulus paradigm. We report on the comprehensive survey of six major SV proteins to show that SV endocytosis in hippocampal neurons at physiological temperature occurs independent of clathrin while the endocytic retrieval of a subset of SV proteins including the vesicular transporters for glutamate and GABA depend on sorting by the clathrin adaptor AP-2. Our findings highlight a clathrin-independent role of the clathrin adaptor AP-2 in the endocytic retrieval of select SV cargos from the presynaptic cell surface and suggest a unified model for the endocytosis of SV membranes at mammalian central synapses.

scholarly journals Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Tania López-Hernández ◽  
Koh-ichiro Takenaka ◽  
Yasunori Mori ◽  
Pornparn Kongpracha ◽  
Shushi Nagamori ◽  
...  
Keyword(s):  
Cell Surface ◽  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Adaptor Protein ◽  
The Reformation ◽  
Comprehensive Survey ◽  
Vesicular Transporters ◽  
Clathrin Adaptor ◽  
Central Synapses

Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Conflicting models have been proposed regarding the mechanisms of SV endocytosis, most notably clathrin/adaptor protein complex 2 (AP-2)-mediated endocytosis and clathrin-independent ultrafast endocytosis. Partitioning between these pathways has been suggested to be controlled by temperature and stimulus paradigm. We report on the comprehensive survey of six major SV proteins to show that SV endocytosis in mouse hippocampal neurons at physiological temperature occurs independent of clathrin while the endocytic retrieval of a subset of SV proteins including the vesicular transporters for glutamate and GABA depend on sorting by the clathrin adaptor AP-2. Our findings highlight a clathrin-independent role of the clathrin adaptor AP-2 in the endocytic retrieval of select SV cargos from the presynaptic cell surface and suggest a revised model for the endocytosis of SV membranes at mammalian central synapses.

NMDA Receptor Antagonists: Repositioning of Memantine as a Multitargeting Agent for Alzheimer's Therapy

2019 ◽  
Vol 25 (33) ◽  
pp. 3506-3518 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Mohammad A. Sufian ◽  
Md. Sahab Uddin ◽  
Mst. Marium Begum ◽  
Shammi Akhter ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Symptomatic Relief ◽  
Critical Role ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Disease Condition ◽  
And Behavior ◽  
With Memory

: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes problems with memory, thinking, and behavior. Currently, there is no drug that can reduce the pathological events of this degenerative disease but symptomatic relief is possible that can abate the disease condition. N-methyl-D-aspartate (NMDA) receptors exert a critical role for synaptic plasticity as well as transmission. Overstimulation of glutamate receptors, predominantly NMDA type, may cause excitotoxic effects on neurons and is recommended as a mechanism for neurodegeneration. Atypical activation of the NMDA receptor has been suggested for AD by synaptic dysfunction. NMDA receptor antagonists especially memantine block the NMDA receptor and can reduce the influx of calcium (Ca2+) ions into neuron, thus, toxic intracellular events are not activated. This review represents the role of NMDA receptors antagonists as potential therapeutic agents to reduce AD. Moreover, this review highlights the repositioning of memantine as a potential novel therapeutic multitargeting agent for AD.

scholarly journals Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

2021 ◽  
Author(s):  
Sarah E Canetta ◽  
Emma S Holt ◽  
Laura J Benoit ◽  
Eric Teboul ◽  
R. Todd Ogden ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Sensitive Period ◽  
Network Function ◽  
Parvalbumin Interneuron ◽  
Circuit Integration ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

Sensitive periods in which experience-driven changes in activity persistently shape circuit function are well-described in sensory cortex. Whether comparable periods govern the development of associative cortical areas, like the prefrontal cortex, remains unclear. Here, we focus on the role of activity in the maturation and circuit integration of prefrontal parvalbumin-expressing interneurons, as these cells play an essential role in sensory cortical maturation and develop in lockstep with overall prefrontal circuit function. We found that transiently decreasing prefrontal parvalbumin activity during peripubertal and adolescent development results in persistent impairments in adult functional connectivity, in vivo network function and set-shifting behavior that can be rescued by targeted activation of these interneurons in the adult animal. In contrast, comparable adult inhibition had no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal parvalbumin maturation and highlight how abnormal parvalbumin activity early in life can persistently alter adult circuit function and behavior.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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