Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar Purkinje cells in vitro

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns

Journal of Neurophysiology ◽

10.1152/jn.00238.2003 ◽

2003 ◽

Vol 90 (4) ◽

pp. 2581-2591 ◽

Cited By ~ 27

Author(s):

F. Aura Ene ◽

Paul H. M. Kullmann ◽

Deda C. Gillespie ◽

Karl Kandler

Keyword(s):

Calcium Channels ◽

Intracellular Calcium ◽

Glutamate Receptors ◽

Cochlear Nucleus ◽

Metabotropic Glutamate Receptors ◽

Lateral Superior Olive ◽

Voltage Gated ◽

Superior Olive ◽

Metabotropic Glutamate ◽

Voltage Gated Calcium Channels

The lateral superior olive (LSO) is a binaural auditory brain stem nucleus that plays a central role in sound localization. Survival and maturation of developing LSO neurons critically depend on intracellular calcium signaling. Here we investigated the mechanisms by which glutamatergic afferents from the cochlear nucleus increase intracellular calcium concentration in LSO neurons. Using fura-2 calcium imaging in slices prepared from neonatal mice, we found that cochlear nucleus afferents can activate all major classes of ionotropic and metabotropic glutamate receptors, each of which contributes to an increase in intracellular calcium. The specific activation of different glutamate receptor classes was dependent on response amplitudes and afferent stimulus patterns. Low-amplitude responses elicited by single stimuli were entirely mediated by calcium-impermeable AMPA/kainate receptors that activated voltage-gated calcium channels. Larger-amplitude responses elicited by either single stimuli or stimulus trains resulted in additional calcium influx through N-methyl-d-aspartate receptors. Finally, high-frequency stimulation also recruited group I and group II metabotropic glutamate receptors, both of which mobilized intracellular calcium. This calcium release in turn activated a strong influx of extracellular calcium through a membrane calcium channel that is distinct from voltage-gated calcium channels. Together, these results indicate that before hearing onset, distinct patterns of afferent activity generate qualitatively distinct types of calcium responses, which likely serve in guiding different aspects of LSO development.

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Long-Term Depression Induced by Postsynaptic Group II Metabotropic Glutamate Receptors Linked to Phospholipase C and Intracellular Calcium Rises in Rat Prefrontal Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.22-09-03434.2002 ◽

2002 ◽

Vol 22 (9) ◽

pp. 3434-3444 ◽

Cited By ~ 66

Author(s):

S. Otani ◽

H. Daniel ◽

M. Takita ◽

F. Crépel

Keyword(s):

Prefrontal Cortex ◽

Intracellular Calcium ◽

Glutamate Receptors ◽

Phospholipase C ◽

Metabotropic Glutamate Receptors ◽

Long Term Depression ◽

Metabotropic Glutamate ◽

Group Ii

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Group 2 metabotropic glutamate receptors induced long term depression in mouse striatal slices

Neuroscience Letters ◽

10.1016/s0304-3940(01)02397-7 ◽

2001 ◽

Vol 316 (3) ◽

pp. 178-182 ◽

Cited By ~ 35

Author(s):

Laetitia Kahn ◽

Gérard Alonso ◽

David Robbe ◽

Joël Bockaert ◽

Olivier J. Manzoni

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Long Term Depression ◽

Striatal Slices ◽

Metabotropic Glutamate ◽

Group 2

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Postsynaptic Current Mediated by Metabotropic Glutamate Receptors in Cerebellar Purkinje Cells

Journal of Neurophysiology ◽

10.1152/jn.1998.80.2.520 ◽

1998 ◽

Vol 80 (2) ◽

pp. 520-528 ◽

Cited By ~ 99

Author(s):

Filippo Tempia ◽

Maria Concetta Miniaci ◽

Davide Anchisi ◽

Piergiorgio Strata

Keyword(s):

Glutamate Receptors ◽

Purkinje Cells ◽

Metabotropic Glutamate Receptors ◽

Parallel Fiber ◽

High Concentration ◽

Metabotropic Glutamate ◽

Group I ◽

Cerebellar Purkinje Cells ◽

Mglur Antagonist ◽

Fiber Stimulation

Tempia, Filippo, Maria Concetta Miniaci, Davide Anchisi, and Piergiorgio Strata. Postsynaptic current mediated by metabotropic glutamate receptors in cerebellar Purkinje cells. J. Neurophysiol. 80: 520–528, 1998. In rat cerebellar slices, repetitive parallel fiber stimulation evokes an inward, postsynaptic current in Purkinje cells with a fast component mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and a slower component mediated by metabotropic glutamate receptors (mGluR). The mGluR-mediated excitatory postsynaptic current (mGluR-EPSC) is evoked selectively by parallel fiber stimulation; climbing fiber stimulation is ineffective. The mGluR-EPSC is elicited most effectively with increasing frequencies of parallel fiber stimulation, from a threshold of 10 Hz to a maximum response at ∼100 Hz. The amplitude of the mGluR-EPSC is a linear function of the number of stimulus pulses without any apparent saturation, even with >10 pulses. Thus mGluRs at the parallel fiber-Purkinje cell synapse can function as linear detectors of the number of spikes in a burst of activity in parallel fibers. The mGluR-EPSC is present from postnatal day 15 and persists into adulthood. It is inhibited by the generic mGluR antagonist (RS)-a-methyl-4-carboxyphenylglycine and by the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid at a concentration selective for mGluR1. Although the intracellular transduction pathway involves a G protein, the putative mediators of mGluR1 (phospholipase C and protein kinase C) are not directly involved, indicating that the mGluR-EPSC studied here is mediated by a different and still unidentified second-messenger pathway. Heparin, a nonselective antagonist of inositol-trisphosphate (IP3) receptors, has no significant effect on the mGluR-EPSC, suggesting that also IP3 might be not required for the response. Buffering intracellular Ca2+ with a high concentration of bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid partially inhibits the mGluR-EPSC, indicating that Ca2+ is not directly responsible for the response but that resting Ca2+ levels exert a tonic potentiating effect on the mGluR-EPSC.

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