Long‐range oscillatory Ca 2+ waves in rat spinal dorsal horn

Synchronous activity of large populations of neurons shapes neuronal networks during development. However, re‐emergence of such activity at later stages of development could severely disrupt the orderly processing of sensory information, e.g. in the spinal dorsal horn. We used Ca 2+ imaging in spinal cord slices of neonatal and young rats to assess under which conditions synchronous activity occurs in dorsal horn. No spontaneous synchronous Ca 2+ transients were detected. However, increasing neuronal excitability by application of 4‐aminopyridine after pretreatment of the slice with blockers of (RS)‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate, γ‐aminobutyric acid (GABA) A and glycine receptors evoked repetitive Ca 2+ waves in dorsal horn. These waves spread mediolaterally with a speed of 1.0 ± 0.1 mm/s and affected virtually every dorsal horn neuron. The Ca 2+ waves were associated with large depolarizing shifts of the membrane potential of participating neurons and were most likely synaptically mediated because they were abolished by blockade of action potentials or N ‐methyl‐ d ‐aspartate (NMDA) receptors. They were most pronounced in the superficial dorsal horn and absent from the ventral horn. A significant proportion of the Ca 2+ waves spread to the contralateral dorsal horn. This seemed to be enabled by disinhibition as primary afferent‐induced dorsal horn excitation crossed the midline only when GABA A and glycine receptors were blocked. Interestingly, the Ca 2+ waves occurred under conditions where AMPA/kainate receptors were blocked. Thus, superficial dorsal horn NMDA receptors are able to sustain synchronous neuronal excitation in the absence of functional AMPA/kainate receptors.