Unmasking group III metabotropic glutamate autoreceptor function at excitatory synapses in the rat CNS
Open Access
- 15 June 2005
- journal article
- research article
- Published by Wiley in The Journal of Physiology
- Vol. 565 (3) , 885-896
- https://doi.org/10.1113/jphysiol.2005.086736
Abstract
Presynaptic group III metabotropic glutamate receptor (mGluR) activation by exogenous agonists (such as l‐2‐amino‐4‐phosphonobutyrate (l‐AP4)) potently inhibit transmitter release, but their autoreceptor function has been questioned because endogenous activation during high‐frequency stimulation appears to have little impact on synaptic amplitude. We resolve this ambiguity by studying endogenous activation of mGluRs during trains of high‐frequency synaptic stimuli at the calyx of Held. In vitro whole‐cell patch recordings were made from medial nucleus of the trapezoid body (MNTB) neurones during 1 s excitatory postsynaptic current (EPSC) trains delivered at 200 Hz and at 37°C. The group III mGluR antagonist (R,S)‐cyclopropyl‐4‐phosphonophenylglycine (CPPG, 300 μm) had no effect on EPSC short‐term depression, but accelerated subsequent recovery time course (τ: 4.6 ± 0.8 s to 2.4 ± 0.4 s, P= 0.02), and decreased paired pulse ratio from 1.18 ± 0.06 to 0.97 ± 0.03 (P= 0.01), indicating that mGluR activation reduced release probability (P). Modelling autoreceptor activation during repetitive stimulation revealed that as P declines, the readily releasable pool size (N) increases so that the net EPSC (NP) is unchanged and short‐term depression proceeds with the same overall time course as in the absence of autoreceptor activation. Thus, autoreceptor action on the synaptic response is masked but the synapse is now in a different state (lower P, higher N). While vesicle replenishment clearly underlies much of the recovery from short‐term depression, our results show that the recovery time course of P also contributes to the reduced response amplitude for 1–2 s. The results show that passive equilibration between N and P masks autoreceptor modulation of the EPSC and suggests that mGluR autoreceptors function to change the synaptic state and distribute metabolic demand, rather than to depress synaptic amplitude.Keywords
This publication has 50 references indexed in Scilit:
- Glutamate transporters and metabotropic receptors regulate excitatory neurotransmission in the medial entorhinal cortex of the ratBrain Research, 2004
- A multi-component model of depression at the calyx of HeldNeurocomputing, 2004
- Synaptic depression in the localization of soundNature, 2003
- Short-Term Synaptic PlasticityAnnual Review of Physiology, 2002
- Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in ratsThe Journal of Physiology, 2002
- Depletion of calcium in the synaptic cleft of a calyx‐type synapse in the rat brainstemThe Journal of Physiology, 1999
- Enhancement of Synaptic Efficacy by Presynaptic GABAB ReceptorsNeuron, 1998
- Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptorsNature, 1997
- Redistribution of synaptic efficacy between neocortical pyramidal neuronsNature, 1996
- The binaural auditory pathway: excitatory amino acid receptors mediate dual timecourse excitatory postsynaptic currents in the rat medial nucleus of the trapezoid bodyProceedings Of The Royal Society B-Biological Sciences, 1993