Editors' ChoiceNeuroscience

GlyR Gets Inflamed

Sci. Signal.  10 Jun 2014:
Vol. 7, Issue 329, pp. ec153
DOI: 10.1126/scisignal.2005578

Long-term potentiation (LTP) of synaptic transmission between neurons is a form of cellular memory. LTP can occur at synapses involving the excitatory neurotransmitter glutamate or the generally inhibitory neurotransmitter GABA (γ-aminobutyric acid). Glycine is another inhibitory neurotransmitter that activates a ligand-gated chloride channel (GlyR), which is structurally related to the GABA receptor. Glycinergic synapses are present on neurons in the dorsal horn of the spinal cord, and glycine- or GABA-mediated inhibition of neuronal transmission can alter the perception of pain, which is also enhanced by inflammation. Chirila et al. found that the proinflammatory cytokine interleukin 1β (IL-1β) promoted LTP at glycinergic synapses. Brief exposure of cultured slices of the mouse spinal cord to IL-1β potentiated electrically evoked inhibitory postsynaptic currents from neurons receiving glycinergic, but not glutaminergic or GABAergic input. IL-1β–mediated potentiation of glycinergic synapses was persistent for the duration of the recording (~30 min) and was inhibited by simultaneous, but not subsequent, application of an IL-1 receptor antagonist. Exposure to IL-1β potentiated both the currents evoked by application of glycine and the amplitude of spontaneous miniature inhibitory postsynaptic currents, which suggested that IL-1β elicited LTP by modulating properties of the postsynaptic neuron. IL-1β–mediated glycinergic LTP was inhibited by depletion of intracellular calcium or inhibition of the kinase p38, which acts downstream of the IL-1 receptor. Inflammation induces activation of purinergic receptors on glial cells, resulting in secretion of IL-1β. Accordingly, exposing slice cultures to a purinergic receptor agonist potentiated glycinergic synapses in an IL-1β–dependent manner. Injecting formalin into the hind paw of mice, which induces inflammation, elicited hyperalgesia and allodynia, and exposure to IL-1β failed to induce glycinergic LTP in neurons in spinal cord slice cultures from these mice. Thus, inflammation induces IL-1β secretion that can induce glycinergic LTP on neurons and thereby promote pain.

A. M. Chirila, T. E. Brown, R. A. Bishop, N. W. Bellono, F. G. Pucci, J. A. Kauer, Long-term potentiation of glycinergic synapses triggered by interleukin 1β. Proc. Natl. Acad. Sci. U.S.A. 111, 8263–8268 (2014). [Abstract] [Full Text]