scholarly journals New light on neurotransmitter-gated receptors: Optical approaches for controlling physiological function

Neuroforum ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. A159-A167
Author(s):  
Andreas Reiner
Keyword(s):  
Nervous System ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Physiological Function ◽  
Control Individual ◽  
Receptor Subtypes ◽  
Receptor Signaling ◽  
Temporal Precision

Abstract Neurotransmitter-gated receptors contribute to synaptic transmission and modulation in many ways. Considering glutamate receptors as an example, it becomes clear that these receptor families are highly diverse and that it is experimentally challenging to disentangle the different functional contributions of closely related receptor subtypes. Pharmacological and genetic methods are now complemented by optogenetic approaches, which allow for controlling receptor signaling with light. Using glutamate receptors as an example, I summarize how tethered photoswitchable ligands can be used to control individual receptor subtypes with high spatial and temporal precision, and in specific cells. These, and similarly exciting approaches, offer new possibilities for probing the function of individual receptors in the nervous system.

scholarly journals Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
David Ramos-Vicente ◽  
Jie Ji ◽  
Esther Gratacòs-Batlle ◽  
Gemma Gou ◽  
Rita Reig-Viader ◽  
...  
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Synaptic Strength ◽  
Phylogenetic Study ◽  
Phylogenetic Groups ◽  
Metazoan Evolution ◽  
Class Iv

Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in metazoans. Importantly, we demonstrate that GluRs have followed different evolutionary histories in separated animal lineages. Our analysis reveals that the present organization of iGluRs into six classes does not capture the full complexity of their evolution. Instead, we propose an organization into four subfamilies and ten classes, four of which have never been previously described. Furthermore, we report a sister class to mGluR classes I-III, class IV. We show that many unreported proteins are expressed in the nervous system, and that new Epsilon receptors form functional ligand-gated ion channels. We propose an updated classification of glutamate receptors that includes our findings.

Metabotropic Glutamate Receptors Regulate N-Methyl-d-Aspartate–Mediated Synaptic Transmission in Nucleus Accumbens

1997 ◽  
Vol 78 (6) ◽  
pp. 3028-3038 ◽  
Author(s):  
Gilles Martin ◽  
Zhiguo Nie ◽  
George R. Siggins
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
Receptor Subtypes ◽  
Metabotropic Glutamate ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Martin, Gilles, Zhiguo Nie, and George R. Siggins. Metabotropic glutamate receptors regulate N-methyl-d-aspartate–mediated synaptic transmission in nucleus accumbens. J. Neurophysiol. 78: 3028–3038, 1997. We recorded intracellularly from core nucleus accumbens (NAcc) neurons in brain slices to study the regulation by metabotropic glutamate receptors (mGluRs) of pharmacologically isolated N-methyl-d-aspartate–mediated excitatory postsynaptic currents (NMDA-EPSCs). Monosynaptic NMDA-EPSCs, evoked by local stimulation, were isolated by superfusion of the non-NMDA and γ-aminobutyric acid-A (GABAA) receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM) and bicuculline (15 μM), respectively. Trans-1-aminocyclopentane-1,3-decarboxylic acid ( trans-ACPD; 50 μM), a nonspecific group 1 and 2 mGluR agonist, had no effect on resting membrane potential (RMP) or input resistance of NAcc neurons. However, it consistently decreased NMDA-EPSC areas (time integrals) dose dependently (1–100 μM; EC50 = 8 μM) and reversibly. The specific group 1 mGluR agonists quisqualate (1–4 μM) and (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 μM) did not mimic the trans-ACPD effect on NMDA-EPSCs, nor did exposure of the slice to the group 1 mGluR antagonist l(+)-2-amino-3-phosphonopropionic acid (l-AP3, 0.4 mM) inhibit the trans-ACPD effect. The putative mGluR1 and mGluR2 antagonist (+)-α-methyl-4-carboxyphenylglycine (MCPG) at 0.5 mM failed to antagonize trans-ACPD effects but at 1 mM blocked them. Both the group 2 mGluR agonist (2S,3S,4S)-α-(carboxycyclopropyl)-glycine (l-CCG-I, 2 μM) and the group 3 mGluR specific agonist l(+)-2-amino-4-phosphonobutyric acid (l-AP4, 20 μM) attenuated NMDA-EPSC areas; the effect of l-AP4 was blocked by the group 3 antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4; 0.5 mM). Exogenously applied NMDA, in the presence of tetrodotoxin to prevent presynaptic effects, induced inward currents that were decreased by 20 μM l-AP4 but not by 10 μM trans-ACPD. These findings suggest that NMDA receptor-mediated neurotransmission in NAcc is under dual inhibitory regulation by group 2 and 3 metabotropic receptor subtypes: l-AP4–sensitive receptors located postsynaptically and those sensitive to trans-ACPD located presynaptically.

scholarly journals The Role of Neuropeptide Y in the Nucleus Accumbens

2021 ◽  
Vol 22 (14) ◽  
pp. 7287
Author(s):  
Masaki Tanaka ◽  
Shunji Yamada ◽  
Yoshihisa Watanabe
Keyword(s):  
Nervous System ◽  
Nucleus Accumbens ◽  
Neuropeptide Y ◽  
Emotional Behavior ◽  
Characteristic Functions ◽  
Receptor Subtypes ◽  
Neuroendocrine Mechanisms ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

Preparation of domoic acid analogues using a bioconversion system, and their toxicity in mice

2021 ◽  
Author(s):  
Yukari Maeno ◽  
Yuichi Kotaki ◽  
Ryuta Terada ◽  
Masafumi Hidaka ◽  
Yuko Cho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chemical Synthesis ◽  
Glutamate Receptors ◽  
Domoic Acid ◽  
Ionotropic Glutamate Receptors ◽  
The Central Nervous System ◽  
Potent Agonist

Domoic acid (1, DA), a member of the natural kainoid family, is a potent agonist of ionotropic glutamate receptors in the central nervous system. The chemical synthesis of DA and...

Synaptic Transmission in the Immune System

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Jens Rettig ◽  
David R. Stevens
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Neuroendocrine Cells ◽  
Regulated Exocytosis ◽  
Protein Receptor ◽  
Immunological Synapses ◽  
Immunological Diseases

AbstractThe release of neurotransmitters at synapses belongs to the most important processes in the central nervous system. In the last decades much has been learned about the molecular mechanisms which form the basis for this fundamental process. Highly regulated exocytosis, based on the SNARE (soluble N-ethylmaleimide-sensitive attachment protein receptor) complex and its regulatory molecules is the signature specialization of the nervous system and is shared by neurons and neuroendocrine cells. Cells of the immune system use a similar mechanism to release cytotoxic materials from secretory granules at contacts with virally or bacterially infected cells or cancer cells, in order to remove these threats. These contact zones have been termed immunological synapses in reference to the highly specific targeted exocytosis of effector molecules. Recent findings indicate that mutations in SNARE or SNARE-interacting proteins are the basis of a number of devastating immunological diseases. While SNARE complexes are ubiquitous and mediate a wide variety of membrane fusion events it is surprising that in many cases the SNARE proteins involved in immunological synapses are the same molecules which mediate regulated exocytosis of transmitters and hormones in neurons and neuroendocrine cells. These similarities raise the possibility that results obtained at immunological synapses may be applicable, in particular in the area of presynaptic function, to neuronal synapses. Since immunological synapses (IS) are assembled and disassembled in about a half an hour, the use of immune cells isolated from human blood allows not only the study of the molecular mechanisms of synaptic transmission in human cells, but is particularly suited to the examination of the assembly and disassembly of these “synapses” via live imaging. In this overview we discuss areas of similarity between synapses of the nervous and immune systems and in the process will refer to results of our experiments of the last few years.

Crosstalk Between Insulin and Toll-like Receptor Signaling Pathways in the Central Nervous system

2014 ◽  
Vol 50 (3) ◽  
pp. 797-810 ◽  
Author(s):  
Fatemeh Hemmati ◽  
Rasoul Ghasemi ◽  
Norlinah Mohamed Ibrahim ◽  
Leila Dargahi ◽  
Zahurin Mohamed ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathways ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
The Central Nervous System

scholarly journals The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4Receptors

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Ramón A. Lorca ◽  
Lorena Varela-Nallar ◽  
Nibaldo C. Inestrosa ◽  
J. Pablo Huidobro-Toro
Keyword(s):  
Amino Acids ◽  
Synaptic Transmission ◽  
Prion Protein ◽  
Adenosine Triphosphate ◽  
Response Curve ◽  
Physiological Function ◽  
Cellular Prion Protein ◽  
Synaptic Activity ◽  
Receptor Subtype ◽  
Concentration Response Curve

Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPCbinds Cu2+through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+of the adenosine triphosphate (ATP)-evoked currents in the P2X4receptor subtype, highlighting a modulatory role for PrPCin synaptic transmission through regulation of Cu2+levels. Here, we study the effect of full-length PrPCin Cu2+inhibition of P2X4receptor when both are coexpressed. PrPCexpression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4receptors. However, the presence of PrPCreduces the inhibition by Cu2+of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+binding domain. Thus, our observations suggest a role for PrPCin modulating synaptic activity through binding of extracellular Cu2+.

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