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 Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Maria Ryazantseva ◽  
Jonas Englund ◽  
Alexandra Shintyapina ◽  
Johanna Huupponen ◽  
Vasilii Shteinikov ◽  
...  
Keyword(s):  
Information Processing ◽  
Genetic Manipulation ◽  
Glutamate Release ◽  
Physiological Mechanism ◽  
Kainate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Development ◽  
Synaptic Circuitry ◽  
Amygdaloid Nuclei ◽  
Dependent Mechanism

Perturbed 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 in rodents the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first 10 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 formation of the glutamatergic circuitry in the amygdala.

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.

Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists

2004 ◽  
Vol 32 (5) ◽  
pp. 881-887 ◽  
Author(s):  
M.P. Johnson ◽  
E.S. Nisenbaum ◽  
T.H. Large ◽  
R. Emkey ◽  
M. Baez ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
G Protein ◽  
Metabotropic Glutamate Receptors ◽  
Focal Point ◽  
Glutamate Release ◽  
Pharmacological Properties ◽  
Allosteric Modulators ◽  
Metabotropic Glutamate ◽  
Subtype Selectivity ◽  
Mglu2 Receptor

Although relatively few G-protein-coupled receptors are Class C, in recent years, this small family of receptors has become a focal point for the discovery of new and exciting allosteric modulators. The mGlu (metabotropic glutamate) receptors are illustrative in the discovery of both positive and/or negative allosteric modulators with unique pharmacological properties. For instance, allosteric modulators of the mGlu2 receptor act as potentiators of glutamate responses in clonal expression systems and in native tissue assays. These potentiators act to increase the affinity of orthosteric agonists for the mGlu2 receptor and shift potency curves for the agonist to the left. In electrophysiological experiments, the potentiators show a unique activation-state-dependent presynaptic inhibition of glutamate release and significantly enhance the receptor-mediated increase in G-protein binding, as seen with autoradiography. Similarly, potentiators of mGlu5 have been described, as well as allosteric antagonists or inverse agonists of mGlu1 and mGlu5. Binding and activity of the modulators have recently indicated that positive and negative allosteric sites can be, but are not necessarily, overlapping. Compared with orthosteric ligands, these modulators display a unique degree of subtype selectivity within the highly conserved mGlu family of receptors and can have very distinct pharmacological properties, such as neuronal frequency-dependent activity. This short review describes some of the unique features of these mGlu1, mGlu2 and mGlu5 allosteric modulators.

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

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.

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