Mediation of Thalamic Sensory Responses In Vivo by ACPD‐activated Excitatory Amino Acid Receptors

Abstract

The existence of the so-called metabotropic excitatory amino acid receptor has been known for some years. Various functions have been suggested for this receptor, but the lack of selective antagonists for (IS, 3R)-aminocyclopentane dicarboxylic acid (ACPD) has precluded the direct demonstration of a functional role for this receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD-sensitive receptors in central neurotransmission, and indicates that these receptors may play an important part in central sensory processes.

Actions of two new antagonists showing selectivity for different sub‐types of metabotropic glutamate receptor in the neonatal rat spinal cord

“…Thus, each of these phenylglycine compounds blocks the (1S,3R)-ACPD-induced depolarization of neonatal rat motoneurones in vitro Eaton et al, 1993b; and the excitation of rat thalamic neurones in vivo (Eaton et al, 1993a). Also, in neurones of the nucleus tractus solitarius (NTS) in the rat brain stem in vitro, these same three phenylglycines antagonize the depression of excitatory postsynaptic currents (e.p.s.cs), the depression of inhibitory postsynaptic currents (i.p.s.cs), the depression of muscimolinduced currents and the potentiation of (RS)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced currents that is effected in each case by (IS,3R)-ACPD (Glaum et al, 1993).…”

“…Also, in neurones of the nucleus tractus solitarius (NTS) in the rat brain stem in vitro, these same three phenylglycines antagonize the depression of excitatory postsynaptic currents (e.p.s.cs), the depression of inhibitory postsynaptic currents (i.p.s.cs), the depression of muscimolinduced currents and the potentiation of (RS)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced currents that is effected in each case by (IS,3R)-ACPD (Glaum et al, 1993). These three phenylglycines selectively block nociceptive responses in rat thalamic neurones in vivo, relative to non-nociceptive sensory responses (Eaton et al, 1993a;Salt et al, 1993), and MCPG has been reported to block the induction of both NMDA-receptor dependent and NMDA receptor-independent long-term potentiation (LTP) in rat hippocampal slices (Bashir et al, 1993).…”

Glutamate receptor functions in sensory relay in the thalamus

“…There seems to be little evidence for a contribution to sensory responses of additional glutamate receptors from in vitro physiological studies, even though experiments have been designed that have attempted to reveal roles for, for example, metabotropic glutamate receptors (Turner & Salt 1998). By contrast, the situation appears to differ in in vivo experiments, where there appear to be sensory responses that have a contribution from mGlu receptors, and it is prob- 2002) able that this re ects recruitment of additional circuitry, possibly corticothalamic inputs (see § 3) (Eaton et al 1993;Salt & Turner 1998b;Rivadulla et al 2002).…”

Metabotropic Glutamate Receptor 5 Is a Disulfide-linked Dimer

“…At least eight mGluRs have been molecularly characterized, and these activate effectors via interactions with heterotrimeric G proteins (1). Thus, the mGluRs are important for neuromodulatory functions, although mGluRs clearly mediate transmission at the retinal photoreceptor-depolarizing bipolar cell synapse (2)(3)(4) and at certain thalamic sensory neurons (5).…”