Electrophysiological and behavioral effects of group I metabotropic glutamate receptors on pallidal neurons in rats.

The globus pallidus plays a critical role in movement regulation. Morphological studies have shown that group I mGluRs including mGluR1 and mGluR5 are expressed in the globus pallidus. Up to now, little is known about the in vivo electrophysiological effects of group I mGluRs on the pallidal neurons. The present study investigated the electrophysiological effects of group I mGluRs on the firing rate of pallidal neurons in anesthetized rats. Single unit in vivo extracellular recordings showed that micropressure ejection of group I mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), increased the spontaneous firing rate of pallidal neurons. DHPG-induced excitation could be blocked by mGluR1 antagonist, (S)-(+)-α-amino-4-carboxy-2-methylb-enzeneacetic acid (LY367385), but not mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP). LY367385 alone had no effect but MPEP alone increased the excitability of pallidal neurons. Unilateral microinjection of DHPG into the globus pallidus induced a contralateral dystonic posturing in the presence of systemic haloperidol administration and this effect could be blocked by LY367385 but not MPEP. The present in vivo electrophysiological and behavioral studies indicate that group I mGluRs could produce excitatory effect on pallidal neurons via mGluR1, and blockade of mGluR5 also has an excitatory effect on pallidal neurons. Our findings suggest that the effects of globus pallidus in movement regulation is partly mediated by group I mGluRs.

Sun XR ，Chen L ，Chen WF ，Yung WH ... -  《-》

Electrophysiological and behavioral effects of group III metabotropic glutamate receptors on pallidal neurons in normal and parkinsonian rats.

The globus pallidus plays a critical role in movement regulation. Glutamate being an important excitatory neurotransmitter modulates the activity of pallidal neurons through both ionotropic and metabotropic glutamate receptors (mGluRs). Morphological studies have shown that group III mGluRs are generally located presynaptically in the globus pallidus. Up to now, little is known about the in vivo electrophysiological effects of group III mGluRs on the pallidal neurons. This study investigated the electrophysiological and behavioral effects of group III mGluRs on pallidal neurons in both normal and 6-hydroxydopamine (6-OHDA) lesioned parkinsonian rats. Micropressure ejection of group III mGluR agonist, L-2-amino-4-phosphonobutyrate (L-AP4), increased or decreased the firing rate of pallidal neurons in both normal and parkinsonian rats. The L-AP4-induced excitatory effects on the lesioned side of parkinsonian rats (117.4 ± 17.2%) were stronger than that in normal rats (64.3 ± 10.1%). While the proportion of neurons that were unresponsive to L-AP4 on the lesioned side of parkinsonian rats (50%) was more than that of normal rats (13%). Unilateral microinjection of L-AP4 into the globus pallidus induced a contralateral dystonic posturing in the presence of systemic haloperidol administration. The selective group III mGluRs antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine, had no effect on pallidal neurons when used alone and could block both L-AP4-induced electrophysiological and behavioral effects. Combining electrophysiological and behavioral findings, we concluded that activation of group III mGluRs modulate the activity of pallidal neurons under both normal and parkinsonian state.

Sun XR ，Chen L ，Chen WF ，Xue Y ，Yung WH ... -  《-》

Down-regulation of metabotropic glutamate receptor 1alpha in globus pallidus and substantia nigra of parkinsonian monkeys.

Kaneda K ，Tachibana Y ，Imanishi M ，Kita H ，Shigemoto R ，Nambu A ，Takada M ... -  《-》

Synaptic activation of mGluR1 generates persistent depression of a fast after-depolarizing potential in CA3 pyramidal neurons.

Burst firing is an important property of hippocampal pyramidal neurons. Group I metabotropic glutamate receptors (mGluRs) produce a multitude of effects on both the synaptic and intrinsic properties of neurons. We investigated whether brief activation of these receptors results in persistent modifications to the intrinsic excitability of rat hippocampal CA3 pyramidal cells (CA3-PCs). In whole-cell current-clamp recordings, current stimuli consisting of filtered, pseudo-random noise produced action potential firing with a mean frequency of ∼1.5-2 Hz. Analysis of spike intervals revealed that this firing included a substantial component (∼20%) of high-frequency (∼100 Hz) bursting activity. Activation of group I mGluRs with (S)-3,5-dihydroxyphenylglycine [(S)-DHPG] selectively eliminated the high-frequency bursts, an effect that persisted > 30 min after (S)-DHPG washout. The fast after-depolarizing potential (ADP) of CA3-PCs is known to be important for generating high-frequency action potential bursting. This ADP was persistently depressed following a short application of (S)-DHPG. This effect was blocked by the mGluR1 antagonist, (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385). In contrast, the depression was resistant to the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, N-methyl-D-aspartate (NMDA) and γ-aminobutyric acid (GABA)(A) antagonists. Unlike other manipulations that generate persistent depression of the ADP in CA3-PCs, DHPG-mediated ADP depression was insensitive to the Kv7 channel inhibitor 10,10-bis(4-Pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and strong intracellular Ca(2+) buffering by 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Synaptic activation of mGluRs in the associational-commissural pathway also resulted in persistent depression of the ADP in postsynaptic CA3-PCs, which was blocked by LY367385. These data represent the first evidence that synaptic activation of mGluR1 can modulate the intrinsic excitability properties of hippocampal neurons.

Brown JT ，Booth CA ，Randall AD 《-》

Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function.

Mannaioni G ，Marino MJ ，Valenti O ，Traynelis SF ，Conn PJ ... -  《-》