Subthreshold membrane potential oscillations as a neuronal disease mechanism: implications from sensory receptors, nociceptive neurons and limbic neurons

Many neurons of the peripheral and central nervous system exhibit oscillations in membrane potential that operate close to the spike threshold. Such neurons are e.g. found in the amygdala, the entorhinal cortex, in nociceptice dorsal root ganglion (DRG) cells and peripheral sensory receptors. In the latter, the oscillations are used for sensitive and differential sensory stimulus encoding and in the cortex the oscillations are presumably used for collective neuronal rhythms (e.g. limbic theta rhythm) and neuronal synchronization and resonance behaviors. In nocieptive DRG cells, these oscillation occur as result to nerve injury and are discussed as a necessary mechanisms for ectopic spike generation and hence neuropathic pain. We were interested to assess the principal mechanisms underlying such oscillations and their resulting modulatory abilities from the perspective of a disease mechanism. In doing so we made use of existing computational models for subthreshold oscillatory neurons and simulated the responses in dependence on (i) synaptic depolarisation (ii) noise, (iii) ionic conductances and (iv) temperature. Our results agree very well with the experimental findings and point to a potential role of subthreshold oscillations in disease states such as neuropathic pain and also within context of pathology involving the amygdala or entorhinal cortex.

Supported by the EU 6th framework program: Network of Excellence BioSim (RA5WP10).