Recent advances in enteric neurobiology: mechanosensitive interneurons

Until recently, it was generally assumed that the only intrinsic sensory neuron, or primary afferent neuron, in the gut was the after-hyperpolarizing AH/Type II neuron. AH neurons excited by local chemical and mechanical stimulation of the mucosa appear to be necessary for activating the peristaltic reflex (oral excitation and anal inhibition of the muscle layers) and anally propagating ring like contractions (peristaltic waves) that depend upon smooth muscle tone. However, our recent findings in the guinea-pig distal colon suggest that different neurochemical classes of interneuron in the colon are also mechanosensitive in that they respond directly to changes in muscle length, rather than muscle tone or tension. These interneurons have electrophysiological properties consistent with myenteric S-neurons. Ascending and descending interneurons respond directly to circumferential stretch by generating an ongoing polarized peristaltic reflex activity (oral excitatory and anal inhibitory junction potentials) in the muscle for as long as the stimulus is maintained. Some descending (nitric oxide synthase +ve) interneurons, on the other hand, appear to respond directly to longitudinal stretch and are involved in accommodation and slow transit of faecal pellets down the colon. This review will present recent evidence that suggests some myenteric S interneurons, in addition to AH neurons, behave as intrinsic sensory neurons.     

Inferior olivary hypertrophy is uncommon in progressive supranuclear palsy

Inferior olivary hypertrophy (IOH) is an uncommon disorder attributed to transsynaptic degeneration and characterized clinically by palatal myoclonus and histopathologically by swollen, fenestrated neurons and bizarre astrocytic gliosis. IOH is usually associated with the interruption of the dentato-olivary tract, most often from cerebrovascular lesions in the dentate nucleus or red nucleus. In progressive supranuclear palsy (PSP), the dentato-olivary tract is consistently affected, and there are reports suggesting that IOH may be relatively common in PSP. To address this issue, the frequency of IOH was investigated in 264 PSP brains. To determine if there was a relationship between IOH and neurofibrillary degeneration in the dentato-olivary pathway, the severity of neurofibrillary degeneration was assessed in the inferior olivary nucleus, cerebellar dentate nucleus and red nucleus in PSP cases with and without IOH. IOH was uncommon in PSP, being found in only 4 of 264 (1.5%) brains, which was not significantly different from the frequency in non-PSP controls (8 of 862; 0.9%). In all non-PSP cases IOH was associated with cerebrovascular lesions, but not in any of the PSP cases with IOH. The severity of neurofibrillary degeneration in the inferior olivary nucleus was significantly greater in PSP cases with IOH than in PSP cases without IOH, whereas there were no significant differences in the cerebellar dentate nucleus and red nucleus. These findings suggest that direct neurofibrillary degeneration in the inferior olivary nucleus may be related to IOH in PSP rather than transsynaptic degeneration.