title: Heterosynaptic long-term potentiation at GABAergic synapses of spinal lamina I neurons.
abstract: Neurons in spinal dorsal horn lamina I play a pivotal role for nociception that critically depends on a proper balance between excitatory and inhibitory inputs. Any modification in synaptic strength may challenge this delicate balance. Long-term potentiation (LTP) at glutamatergic synapses between nociceptive C-fibers and lamina I neurons is an intensively studied cellular model of pain amplification. In contrast, nothing is presently known about long-term changes of synaptic strength at inhibitory synapses in the spinal dorsal horn. Using a spinal cord-dorsal root slice preparation from rats, we show that conditioning stimulation of primary afferent fibers with a stimulating protocol that induces LTP at C-fiber synapses also triggered LTP at GABAergic synapses (LTP(GABA)). This LTP(GABA) was heterosynaptic in nature and was mediated by activation of group I metabotropic glutamate receptors. Opening of ionotropic glutamate receptor channels of the AMPA/KA or NMDA subtype was not required for LTP(GABA). Paired-pulse ratio, coefficient of variation, and miniature IPSCs analysis revealed that LTP(GABA) was expressed presynaptically. Nitric oxide as a retrograde messenger signal mediated this increase of GABA release at spinal inhibitory synapses. This novel form of synaptic plasticity in spinal nociceptive circuits may be an essential mechanism to maintain the relative balance between excitation and inhibition and to improve the signal-to-noise ratio in nociceptive pathways.
authors: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria.
authors: Henning
authors: H
authors: Fenselau
authors: Bernhard
authors: B
authors: Heinke
authors: Jürgen
authors: J
authors: Sandkühler
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid