scholarly journals Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2

2020 ◽  
Vol 45 (9) ◽  
pp. 1454-1462 ◽  
Author(s):  
Kari A. Johnson ◽  
Lucas Voyvodic ◽  
Gabriel C. Loewinger ◽  
Yolanda Mateo ◽  
David M. Lovinger
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate ◽  
Self Stimulation ◽  
Dorsomedial Striatum ◽  
Stimulation Of

scholarly journals Operant self-stimulation of thalamic terminals in the dorsomedial striatum is constrained by metabotropic glutamate receptor 2

2019 ◽  
Author(s):  
Kari A. Johnson ◽  
Lucas Voyvodic ◽  
Yolanda Mateo ◽  
David M. Lovinger
Keyword(s):  
Glutamate Receptor ◽  
Dopamine Release ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Transporter ◽  
Dorsal Striatum ◽  
Critical Determinant ◽  
Metabotropic Glutamate ◽  
Self Stimulation ◽  
Dorsomedial Striatum ◽  
Stimulation Of

ABSTRACTDorsal striatal manipulations including stimulation of dopamine release and activation of medium spiny neurons (MSNs) are sufficient to drive reinforcement-based learning. Glutamatergic innervation of the dorsal striatum by both the cortex and thalamus is a critical determinant of both MSN activity and local regulation of dopamine release. However, the relationship between glutamatergic inputs to the striatum and behavioral reinforcement is not well understood. We sought to evaluate the reinforcing properties of optogenetic stimulation of thalamostriatal terminals, which are associated with vesicular glutamate transporter 2 (Vglut2) expression, in the dorsomedial striatum (DMS), a region implicated in goal-directed operant behaviors. In mice expressing channelrhodopsin-2 (ChR2) under control of the Vglut2 promoter, brief optical stimulation of the DMS reinforces operant lever-pressing behavior. Mice also acquire operant self-stimulation of thalamic terminals in the DMS when ChR2 expression is virally targeted to the intralaminar thalamus. Because the presynaptic G protein-coupled receptor metabotropic glutamate receptor 2 (mGlu2) robustly inhibits glutamate and dopamine release induced by activation of thalamostriatal afferents, we examined the regulation of thalamostriatal self-stimulation by mGlu2. We find that administration of an mGlu2/3 agonist or an mGlu2-selective positive allosteric modulator reduces self-stimulation. In contrast, blockade of these receptors increases thalamostriatal self-stimulation, suggesting that endogenous activation of these receptors negatively modulates the reinforcing properties of thalamostriatal activity. These findings demonstrate that stimulation of thalamic terminals in the DMS is sufficient to reinforce a self-initiated action, and that thalamostriatal reinforcement is constrained by mGlu2 activation.

Progression of Change in NMDA, non-NMDA, and Metabotropic Glutamate Receptor Function at the Developing Corticothalamic Synapse

1998 ◽  
Vol 80 (1) ◽  
pp. 143-154 ◽  
Author(s):  
Peyman Golshani ◽  
Richard A. Warren ◽  
Edward G. Jones
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Voltage Dependence ◽  
Reversal Potential ◽  
Receptor Function ◽  
Internal Solution ◽  
Peak Current ◽  
Metabotropic Glutamate ◽  
Cation Current ◽  
Stimulation Of

Golshani, Peyman, Richard A. Warren, and Edward G. Jones. Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor function at the developing corticothalamic synapse. J Neurophysiol. 80: 143–154, 1998. The development of receptor function at corticothalamic synapses during the first 20 days of postnatal development is described. Whole cell excitatory postsynaptic currents (EPSCs) were evoked in relay neurons of the ventral posterior nucleus (VP) by stimulation of corticothalamic fibers in in vitro slices of mouse brain from postnatal day 1 (P1). During P1–P12, excitatory postsynaptic conductances showed strong voltage dependence at peak current and at 100 ms after the stimulus and were almost completely antagonized by dl−2-amino-5-phosphonopentoic acid (APV), indicating that N-methyl-d-aspartate (NMDA) receptor-mediated currents dominate corticothalamic EPSCs at this time. After P12, in 42% of cells, excitatory postsynaptic conductances showed no voltage-dependence at peak current but still showed voltage-dependence 100-ms poststimulus. This voltage-dependent conductance was antagonized by APV. The nonvoltage-dependent component was APV resistant, showed fast decay, and was antagonized by the nonNMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In the remaining 58% of cells after P12, excitatory postsynaptic conductances showed moderate voltage dependence at peak conductance and strong voltage dependence 100 ms after the stimulus. Analysis of EPSCs before and after APV showed a significant increase in the relative contribution of the non-NMDA conductance after the second postnatal week. From P1 to P16, there was a significant decrease in the time constant of decay of the NMDA EPSC but no change in the voltage dependence of the NMDA response. After P8, slow EPSPs, 1.5–30 s in duration and mediated by metabotropic glutamate receptors (mGluRs), could be evoked by high-frequency stimulation of corticothalamic fibers in the presence of APV and CNQX. Similar slow depolarizations could be evoked by local application of the mGluR agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( t-ACPD) but from P0. Both conductances were blocked by the mGluR antagonist, (RS)-α-methyl-4-carboxyphenylglycine. Hence functional mGluR receptors are present on VP cells from birth, but their synaptic activation at corticothalamic synapses can only be detected after P8. In voltage clamp, the extrapolated reversal potential of the t-ACPD current, with potassium gluconate-based internal solution, was +12 ± 10 (SE) mV, and the measured reversal potential with cesium gluconate-based internal solution was 1.5 ± 9.9 mV, suggesting that the mGluR-mediated depolarization was mediated by a nonselective cation current. Replacement of NaCl in the external solution caused the reversal potential of the current to shift to −18 ± 2 mV, indicating that Na+ is a charge carrier in the current. The current amplitude was not reduced by application of Cs+, Ba2+, and Cd2+, indicating that the t-ACPD current was distinct from the hyperpolarization-activated cation current ( I H) and distinct from certain other previously characterized mGluR-activated, nonselective cation conductances.

Stimulation of oncogenic metabotropic glutamate receptor 1 in melanoma cells activates ERK1/2 via PKCε

2006 ◽  
Vol 18 (8) ◽  
pp. 1279-1286 ◽  
Author(s):  
Yarí E. Marín ◽  
Jin Namkoong ◽  
Karine Cohen-Solal ◽  
Seung-Shick Shin ◽  
Jeffrey J. Martino ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Melanoma Cells ◽  
Metabotropic Glutamate ◽  
Metabotropic Glutamate Receptor 1 ◽  
Stimulation Of

Stimulation of Na-K-2Cl Cotransporter in Neurons by Activation of Non-NMDA Ionotropic Receptor and Group-I mGluRs

2001 ◽  
Vol 85 (6) ◽  
pp. 2563-2575 ◽  
Author(s):  
Stacey L. Schomberg ◽  
Gui Su ◽  
Robert A. Haworth ◽  
Dandan Sun
Keyword(s):  
Dicarboxylic Acid ◽  
Glutamate Receptor ◽  
Cortical Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Dependent Manner ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Intracellular Ca ◽  
Nmda Glutamate Receptor ◽  
Stimulation Of

In a previous study, we found that Na+-K+-2Cl−cotransporter in immature cortical neurons was stimulated by activation of the ionotropic N-methyl-d-aspartate (NMDA) glutamate receptor in a Ca2+-dependent manner. In this report, we investigated whether the Na+-K+-2Cl−cotransporter in immature cortical neurons is stimulated by non-NMDA glutamate receptor–mediated signaling pathways. Expression of the Na+-K+-2Cl−cotransporter and metabotropic glutamate receptors (mGluR1 and 5) was detected in cortical neurons via immunoblotting and immunofluorescence staining. Significant stimulation of cotransporter activity was observed in the presence of both trans-(±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid ( trans-ACPD) (10 μM), a metabotropic glutamate receptor (mGluR) agonist, and (RS)-3,5-dihydroxyphenylglycine (DHPG) (20 μM), a selective group-I mGluR agonist. Both trans-ACPD and DHPG-mediated effects on the cotransporter were eradicated by bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid–AM, a Ca2+ chelator. In addition, DHPG-induced stimulation of the cotransporter activity was inhibited in the presence of mGluRs antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (1 mM) and also with selective mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) (100 μM). A DHPG-induced rise in intracellular Ca2+ in cortical neurons was detected with Fura-2. Moreover, DHPG-mediated stimulation of the cotransporter was abolished by inhibition of Ca2+/CaM kinase II. Interestingly, the cotransporter activity was increased by activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These results suggest that the Na+-K+-2Cl−cotransporter in immature cortical neurons is stimulated by group-I mGluR- and AMPA-mediated signal transduction pathways. The effects are dependent on a rise of intracellular Ca2+.

Sign in / Sign up

Export Citation Format

Share Document