Glycine and glycine receptor signaling in hippocampal neurons: Diversity, function and regulation

doi:10.1016/j.pneurobio.2010.04.008

Progress in Neurobiology

Volume 91, Issue 4, August 2010, Pages 349-361

https://doi.org/10.1016/j.pneurobio.2010.04.008 Get rights and content

Abstract

Glycine is a primary inhibitory neurotransmitter in the spinal cord and brainstem. It acts at glycine receptor (GlyR)-chloride channels, as well as a co-agonist of NMDA receptors (NMDARs). In the hippocampus, the study of GlyRs has largely been under-appreciated due to the apparent absence of glycinergic synaptic transmission. Emerging evidence has shown the presence of extrasynaptic GlyRs in the hippocampus, which exert a tonic inhibitory role, and can be highly regulated under many pathophysiological conditions. On the other hand, besides d-serine, glycine has also been shown to modulate NMDAR function in the hippocampus. The simultaneous activation of excitatory NMDARs and inhibitory GlyRs may provide a homeostatic regulation of hippocampal network function. Furthermore, glycine can regulate hippocampal neuronal activity through GlyR-mediated cross-inhibition of GABAergic inhibition, or through the glycine binding site-dependent internalization of NMDARs. Therefore, hippocampal glycine and its receptors may operate in concert to finely regulate hippocampus-dependent high brain function such as learning and memory. Finally, dysfunction of hippocampal glycine signaling is associated with neuropsychiatric disorders. We speculate that further studies of hippocampal glycine-mediated regulation may help develop novel glycine-based approaches for therapeutic developments.

Introduction

Glycine is a major inhibitory neurotransmitter in the spinal cord and brain stem, acting at strychnine-sensitive glycine receptor (GlyR)-chloride (Cl⁻) channels (Legendre, 2001). In the hippocampus, the study of GlyRs has been largely ignored due to the apparent absence of glycinergic synaptic transmission. However, accumulating evidence shows the presence of non-synaptic GlyRs containing at least the α2 subunit in the hippocampus (Becker et al., 1993, Chattipakorn and McMahon, 2002, Malosio et al., 1991, Racca et al., 1998, Sato et al., 1992, Thio et al., 2003). Consistently, recent studies have revealed a GlyR-mediated tonic inhibition of hippocampal neuronal activity (Keck and White, 2009, Mori et al., 2002, Wang and Xu, 2006, Zhang et al., 2008a).

High brain function such as learning and memory depends critically on the balanced regulation between neuronal excitation and inhibition. As a classical inhibitory neurotransmitter, glycine is unique in that it can act as an agonist of both the inhibitory GlyRs and the excitatory NMDA receptors (NMDARs). Hippocampal glycine has been shown to simultaneously increase GlyR-mediated inhibition and facilitate NMDAR-dependent plasticity in excitatory synapses (Zhang et al., 2008a), thereby providing a potential mechanism underlying balanced regulation between excitation and inhibition in hippocampal networks. Furthermore, glycine can regulate hippocampal inhibition through GlyR-mediated downregulation of another major inhibitory receptor, the GABA_A receptors (GABA_ARs) (Li and Xu, 2002), as well as hippocampal excitation through the glycine binding site-dependent internalization of NMDARs (Nong et al., 2003, Zhang et al., 2008c). According to these observations, we have proposed that hippocampal glycine and its receptors constitute an effective system in homeostatic regulation of hippocampal synaptic and network plasticity (Zhang et al., 2008a) (Fig. 1).

The role of glycine in regulating hippocampal excitatory neurotransmission has been the subject of several authoritative reviews (MacDonald et al., 2006, Mohler et al., 2008, Wood, 1995), which have mainly addressed the issue of neural plasticity mediated via NMDAR glycine binding site. However, our knowledge of the role of glycine and its receptors in hippocampus is still largely incomplete. Here we review recent evidence of functional implications, neuronal circuitries and mechanisms associated with glycine-mediated signaling in hippocampus, with special emphasis on the inhibitory GlyRs.

Section snippets

Glycine transporters in hippocampus

At inhibitory synapses, the postsynaptic actions of glycine are terminated by a rapid reuptake mechanism, which is mainly mediated by glycine transporters (GlyTs). GlyTs, which include GlyT1 and GlyT2, belong to the family of sodium/chloride-dependent transporters (Aragon and Lopez-Corcuera, 2003). GlyT1 is widely expressed in astrocytic glial cells and is thought to control extracellular glycine concentration and regulate excitatory neurotransmission mediated by glycine binding to NMDARs (

Glycine receptors in hippocampus

The GlyR-Cl⁻ channels belong to the nicotinic acetylcholine receptor family of ligand-gated ion channels. To date, four α subunits (α1–α4) and one β subunit of GlyRs have been identified (Lynch, 2004). The α subunit is the obligatory subunit which is capable of forming functional homomeric channels, while the β subunit modulates ligand binding upon co-assembly with α subunits at a proposed 3α:2β stoichiometry (Grudzinska et al., 2005). Another major role of the β subunit is synaptic anchoring

Hippocampal glycine as a co-agonist of NMDA receptors

Besides activating GlyRs, glycine can also act as a co-agonist of NMDARs. Compared to that of GlyRs, the role of NMDARs in the hippocampus is much better established. Several lines of evidence indicate that in the hippocampus, d-serine but not glycine is the endogenous co-agonist of NMDARs (Mothet et al., 2000, Yang et al., 2003). However, under certain conditions, endogenous glycine can also serve as a ligand of NMDARs. In several brain areas, including hippocampus, the blockade of GlyT1 can

Glycine-mediated excitation and inhibition

As discussed above, hippocampal glycine may contribute to the regulation of both hippocampal excitation and inhibition. Especially, hippocampal GlyR-mediated tonic inhibition may be a homeostatic mechanism to overcome the hyperactivity accompanied with enhanced NMDAR functions under some physiological and pathological conditions, such as LTP, ischemia or epilepsy.

A challenge in the study of hippocampal GlyRs is that GlyR-mediated tonic response is too small to be revealed by conventional

Concluding remarks

Although no functional glycinergic synapse has been found in the hippocampus, increasing evidence suggests the presence of hippocampal tonic GlyRs, which can be highly regulated and functional under many physiological or pathological conditions. Besides activating GlyRs, glycine can also act as a co-agonist of hippocampal NMDARs, which are critically associated with long-term neural plasticity. Consequently, glycine can effectively activate GlyRs and NMDARs, and exert its functions in

Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 30830035), the National Basic Research Program of China (No. 2006CB500803), the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX2-YW-R-35), and the Shanghai Municipal Government (09XD1404900). We thank Drs. L.-Y. Liu and D. Bucher for their comments on the manuscript, as well as D.-S. Liu and W.-Q. Xu for their assistance in the preparation of figures.

References (155)

C. Aragon et al.
Structure, function and regulation of glycine neurotransporters
Eur. J. Pharmacol.
(2003)
C.M. Becker et al.
Expression of inhibitory glycine receptors in postnatal rat cerebral cortex
Brain Res.
(1993)
P. Braquet et al.
Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents
J. Ethnopharmacol.
(1991)
E.I. Charych et al.
GABA(A) receptors and their associated proteins: implications in the etiology and treatment of schizophrenia and related disorders
Neuropharmacology
(2009)
L. Danglot et al.
Morphologically identified glycinergic synapses in the hippocampus
Mol. Cell Neurosci.
(2004)
A.C. Flint et al.
Nonsynaptic glycine receptor activation during early neocortical development
Neuron
(1998)
S. Fucile et al.
Fast potentiation of glycine receptor channels of intracellular calcium in neurons and transfected cells
Neuron
(2000)
A. Geerlings et al.
Characterization of the interactions between the glycine transporters GLYT1 and GLYT2 and the SNARE protein syntaxin 1A
FEBS Lett.
(2000)
J. Gomeza et al.
Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition
Neuron
(2003)
J. Gomeza et al.
Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality
Neuron
(2003)

F. Grassi

Cl(-)-mediated interaction between GABA and glycine currents in cultured rat hippocampal neurons

Brain Res.

(1992)

J. Grudzinska et al.

The beta subunit determines the ligand binding properties of synaptic glycine receptors

Neuron

(2005)

R.J. Harvey et al.

The genetics of hyperekplexia: more than startle!

Trends Genet.

(2008)

K. Hirzel et al.

Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission

Neuron

(2006)

P. Ju et al.

Zn²⁺ inhibits glycine transport by glycine transporter subtype 1b

J. Biol. Chem.

(2004)

K. Kawa

Glycine facilitates transmitter release at developing synapses: a patch clamp study from Purkinje neurons of the newborn rat

Brain Res. Dev. Brain Res.

(2003)

T. Kira et al.

Kinetics of sevoflurane action on GABA- and glycine-induced currents in acutely dissociated rat hippocampal neurons

Neuroscience

(1998)

J. Kirsch et al.

Widespread expression of gephyrin, a putative glycine receptor-tubulin linker protein, in rat brain

Brain Res.

(1993)

E.L. Kondratskaya et al.

The beta subunit increases the ginkgolide B sensitivity of inhibitory glycine receptors

Neuropharmacology

(2005)

E.L. Kondratskaya et al.

Ginkgolide B preferentially blocks chloride channels formed by heteromeric glycine receptors in hippocampal pyramidal neurons of rat

Brain Res. Bull.

(2004)

E.L. Kondratskaya et al.

Inhibition of hippocampal LTP by ginkgolide B is mediated by its blocking action on PAF rather than glycine receptors

Neurochem. Int.

(2004)

O.A. Krishtal et al.

Rapid extracellular pH transients related to synaptic transmission in rat hippocampal slices

Brain Res.

(1987)

B. Laube et al.

Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses?

Trends Pharmacol. Sci.

(2002)

D.J. Laurie et al.

Ligand affinities at recombinant N-methyl-d-aspartate receptors depend on subunit composition

Eur. J. Pharmacol.

(1994)

S. Levi et al.

Homeostatic regulation of synaptic GlyR numbers driven by lateral diffusion

Neuron

(2008)

Y. Li et al.

Asymmetric cross-inhibition between GABA_A and glycine receptors in rat spinal dorsal horn neurons

J. Biol. Chem.

(2003)

J.M. Loftis et al.

The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications

Pharmacol. Ther.

(2003)

H. Lu et al.

The general anesthetic pentobarbital slows desensitization and deactivation of the glycine receptor in the rat spinal dorsal horn neurons

J. Biol. Chem.

(2002)

T. Lu et al.

Glycinergic transmission shaped by the corelease of GABA in a mammalian auditory synapse

Neuron

(2008)

Y.M. Lu et al.

Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP

Neuron

(2000)

J.W. Lynch

Native glycine receptor subtypes and their physiological roles

Neuropharmacology

(2009)

G. Maksay et al.

Subunit-specific modulation of glycine receptors by neurosteroids

Neuropharmacology

(2001)

G. Meyer et al.

Identification of a gephyrin binding motif on the glycine receptor beta subunit

Neuron

(1995)

I. Mody et al.

Bridging the cleft at GABA synapses in the brain

Trends Neurosci.

(1994)

H. Mohler et al.

Regulation of cognition and symptoms of psychosis: focus on GABA(A) receptors and glycine transporter 1

Pharmacol. Biochem. Behav.

(2008)

L.G. Aguayo et al.

Ethanol modulation of the gamma-aminobutyric acid_A- and glycine-activated Cl⁻ current in cultured mouse neurons

J. Pharmacol. Exp. Ther.

(1994)

S. Ahmadi et al.

PGE(2) selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons

Nat. Neurosci.

(2002)

A. Araque et al.

SNARE protein-dependent glutamate release from astrocytes

J. Neurosci.

(2000)

S.Y. Assaf et al.

Release of endogenous Zn²⁺ from brain tissue during activity

Nature

(1984)

K.R. Aubrey et al.

Molecular basis for proton regulation of glycine transport by glycine transporter subtype 1b

Mol. Pharmacol.

(2000)

J.E. Belforte et al.

Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes

Nat. Neurosci.

(2010)

Y. Ben-Ari et al.

The multiple facets of gamma-aminobutyric acid dysfunction in epilepsy

Curr. Opin. Neurol.

(2005)

R. Bergeron et al.

Modulation of N-methyl-d-aspartate receptor function by glycine transport

Proc. Natl. Acad. Sci. U.S.A.

(1998)

A.B. Bloomenthal et al.

Biphasic modulation of the strychnine-sensitive glycine receptor by Zn²⁺

Mol. Pharmacol.

(1994)

H.G. Breitinger et al.

The inhibitory glycine receptor: prospects for a therapeutic orphan?

Curr. Pharm. Des.

(1998)

T.M. Bridges et al.

Design of potent GlyT1 inhibitors: in vitro and in vivo profiles

Curr. Opin. Mol. Ther.

(2008)

M. Calamai et al.

Gephyrin oligomerization controls GlyR mobility and synaptic clustering

J. Neurosci.

(2009)

V.B. Caraiscos et al.

Tyrosine kinases enhance the function of glycine receptors in rat hippocampal neurons and human alpha(1)beta glycine receptors

J. Physiol.

(2002)

C. Charrier et al.

Cytoskeleton regulation of glycine receptor number at synapses and diffusion in the plasma membrane

J. Neurosci.

(2006)

S.C. Chattipakorn et al.

Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices

J. Neurophysiol.

(2002)

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Glycine and glycine receptor signaling in hippocampal neurons: Diversity, function and regulation

Abstract

Introduction

Section snippets

Glycine transporters in hippocampus

Glycine receptors in hippocampus

Hippocampal glycine as a co-agonist of NMDA receptors

Glycine-mediated excitation and inhibition

Concluding remarks

Acknowledgements

Eur. J. Pharmacol.

Brain Res.

J. Ethnopharmacol.

Neuropharmacology

Mol. Cell Neurosci.

Neuron

Neuron

FEBS Lett.

Neuron

Neuron

Brain Res.

Neuron

Trends Genet.

Neuron

J. Biol. Chem.

Brain Res. Dev. Brain Res.

Neuroscience

Brain Res.

Neuropharmacology

Brain Res. Bull.

Neurochem. Int.

Brain Res.

Trends Pharmacol. Sci.

Eur. J. Pharmacol.

Neuron

J. Biol. Chem.

Pharmacol. Ther.

J. Biol. Chem.

Neuron

Neuron

Neuropharmacology

Neuropharmacology

Neuron

Trends Neurosci.

Pharmacol. Biochem. Behav.

Ethanol modulation of the gamma-aminobutyric acidA- and glycine-activated Cl− current in cultured mouse neurons

J. Pharmacol. Exp. Ther.

PGE(2) selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons

Nat. Neurosci.

SNARE protein-dependent glutamate release from astrocytes

J. Neurosci.

Release of endogenous Zn2+ from brain tissue during activity

Nature

Molecular basis for proton regulation of glycine transport by glycine transporter subtype 1b

Mol. Pharmacol.

Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes

Nat. Neurosci.

The multiple facets of gamma-aminobutyric acid dysfunction in epilepsy

Curr. Opin. Neurol.

Modulation of N-methyl-d-aspartate receptor function by glycine transport

Proc. Natl. Acad. Sci. U.S.A.

Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+

Mol. Pharmacol.

The inhibitory glycine receptor: prospects for a therapeutic orphan?

Curr. Pharm. Des.

Design of potent GlyT1 inhibitors: in vitro and in vivo profiles

Curr. Opin. Mol. Ther.

Gephyrin oligomerization controls GlyR mobility and synaptic clustering

J. Neurosci.

Tyrosine kinases enhance the function of glycine receptors in rat hippocampal neurons and human alpha(1)beta glycine receptors

J. Physiol.

Cytoskeleton regulation of glycine receptor number at synapses and diffusion in the plasma membrane

J. Neurosci.

Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices

J. Neurophysiol.

Ethanol modulation of the gamma-aminobutyric acid_A- and glycine-activated Cl⁻ current in cultured mouse neurons

Release of endogenous Zn²⁺ from brain tissue during activity

Biphasic modulation of the strychnine-sensitive glycine receptor by Zn²⁺