scholarly journals Disinhibitory recruitment of NMDA receptor pathways in retina

2014 ◽  
Vol 112 (1) ◽  
pp. 193-203 ◽  
Author(s):  
Santhosh Sethuramanujam ◽  
Malcolm M. Slaughter
Keyword(s):  
Nmda Receptor ◽  
Glutamate Receptors ◽  
Presynaptic Inhibition ◽  
Amacrine Cell ◽  
Glutamate Release ◽  
Relative Strength ◽  
Bipolar Cells ◽  
Ionotropic Glutamate Receptors ◽  
Nmdar Activation ◽  
On And Off Pathways

Glutamate release at bipolar to ganglion cell synapses activates NMDA and AMPA/kainic acid (KA) ionotropic glutamate receptors. Their relative strength determines the output signals of the retina. We found that this balance is tightly regulated by presynaptic inhibition that preferentially suppresses NMDA receptor (NMDAR) activation. In transient ON-OFF neurons, block of GABA and glycine feedback enhanced total NMDAR charge by 35-fold in the ON response and 9-fold in the OFF compared with a 1.7-fold enhancement of AMPA/KA receptors. Blocking only glycine receptors enhanced the NMDAR excitatory postsynaptic current 10-fold in the ON and 2-fold in the OFF pathway. Blocking GABAA or GABAC receptors (GABACRs or GABAARs) produced small changes in total NMDAR charge. When both GABAARs and GABACRs were blocked, the total NMDAR charge increased ninefold in the ON and fivefold in the OFF pathway. This exposed a strong GABACR feedback to bipolar cells that was suppressed by serial amacrine cell synapses mediated by GABAARs. The results indicate that NMDAR currents are large but latent, held in check by dual GABA and glycine presynaptic inhibition. One example of this controlled NMDAR activation is the cross talk between ON and OFF pathways. Blocking the ON pathway increased NMDAR relative strength in the OFF pathway. Stimulus prolongation similarly increased the NMDAR relative strength in the OFF response. This NMDAR enhancement was produced by a diminution in GABA and glycine feedback. Thus the retinal network recruits NMDAR pathways through presynaptic disinhibition.

Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina

2005 ◽  
Vol 22 (4) ◽  
pp. 469-477 ◽  
Author(s):  
DAVID J. CALKINS
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Ultrastructural Localization ◽  
Bipolar Cells ◽  
Ionotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
Signal Light ◽  
G Protein Coupled ◽  
Microscopic Distribution

The separation of OFF pathways that signal light decrements from ON pathways that signal light increments occurs at the first retinal synapse. The dendrites of OFF bipolar cells abut the cone pedicle at basal positions distal to the site of glutamate release and express ligand-gated or ionotropic glutamate receptors (GluR). The dendrites of ON bipolar cells penetrate narrow invaginations of the cone pedicle proximal to the site of release and express the G-protein-coupled, metabotropic glutamate receptor, mGluR6. However, recent studies demonstrating the expression of GluR subunits in the rodent rod bipolar cell, known to yield an ON response to light, call this basic segregation of receptors into question. The light-microscopic distribution of many glutamate receptors in the primate retina is now well established. We reexamined their ultrastructural localization in the outer retina ofMacaca fascicularisto test systematically whether invaginating dendrites at the cone synapse, presumably from ON bipolar cells, also express one or more ionotropic subunits. Using preembedding immunocytochemistry for electron microscopy, we quantified the distribution of the AMPA-sensitive subunits GluR2/3 and GluR4 and of the kainate-sensitive subunits GluR6/7 across 207 labeled dendrites occupying specific morphological loci at the cone pedicle. We report, in agreement with published investigations, that the majority of labeled processes for GluR2/3 (70%) and GluR4 (67%) either occupy basal positions or arise from horizontal cells. For GluR6/7, we find a significantly lower fraction of labeled processes at these positions (47%). We also find a considerable number of labeled dendrites for GluR2/3 (10%), GluR4 (21%), and GluR6/7 (18%) at invaginating positions. Surprisingly, for each subunit, the remainder of labeled processes corresponds to “fingers” of presynaptic cytoplasm within the cone invagination.

Depressor and bradycardic responses to microinjections of endomorphin-2 into the NTS are mediated via ionotropic glutamate receptors

2004 ◽  
Vol 287 (4) ◽  
pp. R715-R728 ◽  
Author(s):  
Ken Kasamatsu ◽  
Vineet C. Chitravanshi ◽  
Hreday N. Sapru
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Glutamate Receptors ◽  
Opioid Receptors ◽  
Nucleus Tractus Solitarius ◽  
Glutamate Release ◽  
Nmda Receptor Antagonist ◽  
Gabaergic Neurons ◽  
Ionotropic Glutamate Receptors ◽  
Nerve Terminals

The presence of endomorphin-like immunoreactivity has been reported in the nucleus tractus solitarius (NTS). It was hypothesized that endomorphins may play a role in cardiovascular regulation in the medial subnucleus of the NTS (mNTS). Endomorphin-2 (E-2, 0.1–4 mmol/l) was microinjected (100 nl) into the mNTS of urethane-anesthetized, artificially ventilated, adult male Wistar rats. E-2 (0.2 mmol/l) elicited decreases in mean arterial pressure (40 ± 3.5 mmHg) and heart rate (50 ± 7.0 beats/min). These responses were blocked by prior microinjections of naloxonazine (1 mmol/l) into the mNTS. Responses to microinjections of E-2 into the mNTS were abolished by prior combined microinjections of d-2-amino-7-phosphonoheptanoic acid (an NMDA receptor antagonist, 5 mmol/l) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[ f]quinoxaline-7-sulfonamide disodium (a non-NMDA receptor antagonist, 2 mmol/l) into the mNTS. These results were confirmed by extracellular neuronal recordings. Blockade of GABA receptors in the mNTS by prior combined microinjections of gabazine (a GABAA receptor antagonist, 2 mmol/l) and 2-hydroxysaclofen (a GABAB receptor antagonist, 100 mmol/l) also blocked the responses to E-2. It was concluded that 1) the depressor and bradycardic responses to microinjections of E-2 into the mNTS are mediated via μ1-opioid receptors as well as ionotropic glutamate receptors, 2) GABAergic neurons in the mNTS, which may inhibit the release of glutamate from nerve terminals, are inhibited by E-2 via μ1-opioid receptors, and 3) disinhibition caused by the inhibition of GABAergic neurons by E-2 may result in an increase in the glutamate release from nerve terminals, which, in turn, may elicit depressor and bradycardic responses.

Facilitation of glutamate release by ionotropic glutamate receptors in osteoblasts

2002 ◽  
Vol 297 (3) ◽  
pp. 452-458 ◽  
Author(s):  
Eiichi Hinoi ◽  
Sayumi Fujimori ◽  
Takeshi Takarada ◽  
Hideo Taniura ◽  
Yukio Yoneda
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Release ◽  
Ionotropic Glutamate Receptors

scholarly journals Kainate-type of glutamate receptors regulate wiring of intrinsic glutamatergic connectivity in the amygdala

2019 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Asla Pitkänen ◽  
...  
Keyword(s):  
Information Processing ◽  
Glutamate Receptors ◽  
G Protein ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

SummaryPerturbed information processing in the amygdala has been implicated in developmentally originating neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei. We demonstrate that the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first ten postnatal days, before external inputs underlying amygdala dependent behaviors emerge. During this restricted period of synaptic development, kainate-type of ionotropic glutamate receptors (KARs) are highly expressed in the BLA and tonically activated to regulate glutamate release via a G-protein dependent mechanism. Genetic manipulation of this endogenous KAR activity locally in the newborn LA perturbed development of glutamatergic input to CeA, identifying KARs as a physiological mechanism regulating wiring of the intrinsic glutamatergic circuitry in the amygdala.

scholarly journals Pro-survival signalling from the NMDA receptor

2006 ◽  
Vol 34 (5) ◽  
pp. 936-938 ◽  
Author(s):  
G.E. Hardingham
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Glutamate Receptors ◽  
Receptor Activity ◽  
Ionotropic Glutamate Receptors ◽  
Acute Trauma ◽  
Mammalian Central Nervous System ◽  
Clinical Benefits ◽  
Opposing Effects

Ca2+ influx through the NMDA (N-methyl-D-aspartate) subtype of ionotropic glutamate receptors plays a Jekyll and Hyde role in the mammalian central nervous system. While it mediates excitotoxic death triggered by stroke and other acute trauma, there is growing evidence that physiological levels of NMDA receptor activity promote survival. Understanding the mechanisms that underlie these opposing effects may lead to strategies to selectively block pro-death signalling, which could have considerable clinical benefits.

scholarly journals Ionotropic glutamate receptors of amacrine cells of the mouse retina

2006 ◽  
Vol 23 (1) ◽  
pp. 79-90 ◽  
Author(s):  
OLIVIA N. DUMITRESCU ◽  
DARIO A. PROTTI ◽  
SRIPARNA MAJUMDAR ◽  
HANNS ULRICH ZEILHOFER ◽  
HEINZ WÄSSLE
Keyword(s):  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Amacrine Cell ◽  
Fluorescent Protein ◽  
Lucifer Yellow ◽  
Amacrine Cells ◽  
Ionotropic Glutamate Receptors ◽  
Mouse Retina ◽  
Wide Field ◽  
Transgenic Mouse Line

The mammalian retina contains approximately 30 different morphological types of amacrine cells, receiving glutamatergic input from bipolar cells. In this study, we combined electrophysiological and pharmacological techniques in order to study the glutamate receptors expressed by different types of amacrine cells. Whole-cell currents were recorded from amacrine cells in vertical slices of the mouse retina. During the recordings the cells were filled with Lucifer Yellow/Neurobiotin allowing classification as wide-field or narrow-field amacrine cells. Amacrine cell recordings were also carried out in a transgenic mouse line whose glycinergic amacrine cells express enhanced green fluorescent protein (EGFP). Agonist-induced currents were elicited by exogenous application of NMDA, AMPA, and kainate (KA) while holding cells at −75 mV. Using a variety of specific agonists and antagonists (NBQX, AP5, cyclothiazide, GYKI 52466, GYKI 53655, SYM 2081) responses mediated by AMPA, KA, and NMDA receptors could be dissected. All cells (n= 300) showed prominent responses to non-NMDA agonists. Some cells expressed AMPA receptors exclusively and some cells expressed KA receptors exclusively. In the majority of cells both receptor types could be identified. NMDA receptors were observed in about 75% of the wide-field amacrine cells and in less than half of the narrow-field amacrine cells. Our results confirm that different amacrine cell types express distinct sets of ionotropic glutamate receptors, which may be critical in conferring their unique temporal responses to this diverse neuronal class.

scholarly journals Different types of retinal inhibition have distinct neurotransmitter release properties

2015 ◽  
Vol 113 (7) ◽  
pp. 2078-2090 ◽  
Author(s):  
Johnnie M. Moore-Dotson ◽  
Justin S. Klein ◽  
Reece E. Mazade ◽  
Erika D. Eggers
Keyword(s):  
Bipolar Cell ◽  
Neurotransmitter Release ◽  
Amacrine Cell ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Bipolar Cells ◽  
Glycine Release ◽  
Presynaptic Mechanisms ◽  
Rod Bipolar Cells

Neurotransmitter release varies between neurons due to differences in presynaptic mechanisms such as Ca2+ sensitivity and timing. Retinal rod bipolar cells respond to brief dim illumination with prolonged glutamate release that is tuned by the differential release of GABA and glycine from amacrine cells in the inner retina. To test if differences among types of GABA and glycine release are due to inherent amacrine cell release properties, we directly activated amacrine cell neurotransmitter release by electrical stimulation. We found that the timing of electrically evoked inhibitory currents was inherently slow and that the timecourse of inhibition from slowest to fastest was GABAC receptors > glycine receptors > GABAA receptors. Deconvolution analysis showed that the distinct timing was due to differences in prolonged GABA and glycine release from amacrine cells. The timecourses of slow glycine release and GABA release onto GABAC receptors were reduced by Ca2+ buffering with EGTA-AM and BAPTA-AM, but faster GABA release on GABAA receptors was not, suggesting that release onto GABAA receptors is tightly coupled to Ca2+. The differential timing of GABA release was detected from spiking amacrine cells and not nonspiking A17 amacrine cells that form a reciprocal synapse with rod bipolar cells. Our results indicate that release from amacrine cells is inherently asynchronous and that the source of nonreciprocal rod bipolar cell inhibition differs between GABA receptors. The slow, differential timecourse of inhibition may be a mechanism to match the prolonged rod bipolar cell glutamate release and provide a way to temporally tune information across retinal pathways.

Activation of Ionotropic Glutamate Receptors on Peripheral Axons of Primary Motoneurons Mediates Transmitter Release at the Zebrafish NMJ

2004 ◽  
Vol 91 (2) ◽  
pp. 828-840 ◽  
Author(s):  
Keith J. Todd ◽  
Carrie A. B. Slatter ◽  
Declan W. Ali
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Glutamate Receptors ◽  
Glutamate Uptake ◽  
Nmda Receptor Antagonist ◽  
Ionotropic Glutamate Receptors ◽  
Ach Release ◽  
Specific Staining ◽  
Larval Zebrafish ◽  
Specific Antagonist

The development and function of the vertebrate neuromuscular junction (NMJ) is continually being redefined. Previous studies have indicated that glutamate may play a role in the development or function of the NMJ by associating with presynaptic receptors. We have used larval zebrafish ( Danio rerio) to investigate the presence of presynaptic ionotropic glutamate receptors (iGluRs) at the NMJ in vivo. In whole-mount zebrafish larvae, antibody staining directed to NR2A subunits colocalized with specific staining of motoneuron axon tracts. Whole cell voltage-clamp recordings of miniature endplate currents (mEPCs) from axial white muscle were performed during application of iGluR agonists and antagonists. Local perfusion of the NMJ with iGluR agonists resulted in significant increases in the frequency of spontaneous acetylcholine (ACh) release. These increases were blocked by the N-methyl-d-aspartate (NMDA) receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (50 μM) and by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (50 μM). Further pharmacological investigation revealed no effect of the kainate receptor-specific antagonist (2S,4R)-4-methylglutamate (10 μM) on kainate-induced rises in the frequency of spontaneous ACh release. However, these were blocked with the AMPA receptor-specific antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (50 μM). Application of glutamate (1 mM) in the presence of the glutamate uptake inhibitor d-threo-β-benzyloxyaspartate(200 μM) resulted in a significant increase in the frequency of mEPCs. These results suggest the presence of AMPA and NMDA receptors in association with motoneuron axons of larval zebrafish.

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