Plasticity of synaptic inhibition in mouse spinal cord lamina II neurons during early postnatal development and after inactivation of the glycine receptor alpha3 subunit gene.

Abstract

Synaptic inhibition mediated by GABA(A) receptors and glycine receptors (GlyRs) in the outer laminae of the spinal cord dorsal horn efficiently filters ascending nociceptive messages, controlling pathological pain symptoms. However, although many studies have utilized transgenic models to study spinal nociceptive processing, very little is known about the development of functional inhibitory synapses onto these interneurons in mice. Here we report that most interneurons in lamina II are placed under phasic control by both GABAergic and glycinergic synapses, a number of which exhibit dual GABA/glycine co-release. A developmental switch is also apparent: a subpopulation of lamina II interneurons controlled exclusively by either GABAergic or glycinergic synapses becomes detectable only after postnatal days 15 and 21, respectively. Using mice older than postnatal day 21, we also characterized the plastic changes in glycinergic transmission resulting from the inactivation of the GlyR alpha3 subunit gene, a key player in inflammatory pain pathways. This allowed us to demonstrate that synapses containing GlyR alpha3 contribute in large part to synaptic inhibition in lamina II. In Glra3 knockout mice, we found that synaptic currents at the remaining glycinergic synapses, containing GlyR alpha1, showed faster decay kinetics with unchanged amplitudes but increased frequency. These findings explain the absence of any basal nociceptive hypersensitivity in Glra3 knockout mice, as GlyR alpha1 is still available for mediating synaptic inhibition at lamina II synapses, but cannot be modulated by the prostaglandin-E-prostanoid type 2 (EP2) receptor-protein kinase A signalling cascade. Our results clearly demonstrate that presynaptic GABA/glycine release properties are influenced by the nature and complexity of postsynaptic inhibitory receptor subtypes.

• Authors: M Rajalu, U C Müller, A Caley, R J Harvey, P Poisbeau
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 30 Issue 12 Pg. 2284-92 (Dec 2009) ISSN: 1460-9568 [Electronic] France
• PMID: 20092571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, GABA-A
• Receptors, Glycine
• glycine receptor alpha3 subunit
• gamma-Aminobutyric Acid
• Glycine

Topics

• Aging
• Animals
• Glycine (metabolism)
• In Vitro Techniques
• Inhibitory Postsynaptic Potentials (physiology)
• Interneurons (physiology)
• Kinetics
• Male
• Membrane Potentials (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neural Inhibition (physiology)
• Neuronal Plasticity (physiology)
• Neurons (physiology)
• Receptors, GABA-A (metabolism)
• Receptors, Glycine (genetics, metabolism)
• Spinal Cord (growth & development, physiology)
• Synapses (physiology)
• Synaptic Transmission (physiology)
• gamma-Aminobutyric Acid (metabolism)