Caracterización y estudio funcional de neuronas con actividad espontánea en el asta dorsal de la médula espinal

Resumo

The dorsal horn of the spinal cord is an important region for the processing of nociceptive information. The neurons of this area can show spontaneous activity in the absence of external stimulation, a phenomenon that has not been studied deeply enough and therefore its function is still unknown. In order to study this activity, in this work we performed extracellular recordings with multi-electrode arrays in a spinal cord preparation maintained in vitro. Additionally, we recorded the spontaneous activity of primary afferents from the dorsal roots contained in the preparation. It was found that spinal neurons showed distinct patterns of spontaneous activity, distinguishable according to regularity and burst clustering of action potentials. The activity of these neurons could originate either on the basis of synaptic input received from other elements of the circuit or by intrinsic automatism. In the latter case, we proved that the h-current and the persistent sodium current were responsible for the generation of this intrinsic firing. The spontaneous neurons established correlation relationships among themselves involving a large number of elements, forming what we called population bursts. These were closely related to the spontaneous activity recorded in the primary afferents: dorsal root potentials and dorsal root reflexes. Dorsal root reflexes allowed the identification of individual primary afferents, so we could analyze functional connectivity between dorsal horn neurons and primary afferents. For this purpose, we developed a machine learning algorithm that allowed us to identify spinal neurons that could act as presynaptic and postsynaptic elements with respect to afferents. Finally, we assessed the influence of the descending control system on this activity, finding that both noradrenaline and serotonin exert a very specific control over spontaneous activity, with synchronous events and correlated afferent activity being especially sensitive to these neurotransmitters.