Regionally defective colonization of the terminal bowel by the precursors of enteric neurons in lethal spotted mutant mice

In order to gain insight into the process of colonization of the bowel by the neural crest-derived precursors of enteric neurons, the development of the enteric nervous system was examined in lethal spotted mutant mice, a strain in which a segment of bowel is congenitally aganglionic. In addition, nerve fibers within the ganglionic and aganglionic zones of the gut of adult mutant mice were investigated with respect to their content of acetylcholinesterase, immunoreactive substance P, vasoactive intestinal polypeptide and serotonin, and their ability to take up [³Hserotonin. In both the fetal gut of developing mutant mice and in the mature bowel of adult animals abnormalities were limited to the terminal 2 mm of colon. The enteric nervous system in the proximal alimentary tract was indistinguishable from that of control animals for all of the parameters examined. In the terminal bowel, the normal plexiform pattern of the innervation and ganglion cell bodies were replaced by a coarse reticulum of nerve fibers that stained for acetylcholineserase and were continuous with extrinsic nerves running between the colon and the pelvic plexus. These coarse nerve bundles contained greatly reduced numbers of fibers that displayed substance P- and vasoactive intestinal polypeptide-like immunoreactivity, but a serotonergic innervation was totally missing from the aganglionic bowel. During development, acetylcholineserase and uptake of [³Hserotonin appeared in neural elements in the foregut of mutant mice on the 12th day of embryonic life (E12), about the same time these markers appeared in the forgut in normal mice. By day E14, neurons expressing one or the other marker were recognizable as far distally as about 2 mm from the anus. The appearance of neurons in segments of gut grown for 2 weeks as expiants in culture was used as an assay for the presence of neuronal progenitor cells in the segments of fetal bowel at the time of explantation. Both acetyl- cholinesterase activity and uptake of [³Hserotonin developed in neuronsin vitro in expiants of proximal bowel between days E10 and E17. At all times, however, the terminal 2mm of mutant but not normal fetal gut gave rise to aneuronal cultures. In some mutant mice rare, small, ectopically-situated pelvic ganglia were found just outside aganglionic segments of fetal colon. Uptake of [³Hserotonin, normally a marker for intrinsic enteric neurites, was found in these ganglia.The experiments suppport the hypothesis that the terminal 2 mm of the gut in lethal spotted mutant mice is intrinsically abnormal and thus cannot be colonized by the precursors of enteric neurons. The defect seems to be specific in that both cells and processes of intrinsic enteric neurons, including all serotonergic and most peptidergic neurites, seem to be excluded from the abnormal region while extrinsic nerve fibers, including sympathetic and sensory axons, are able to enter the aganglionic zones. Since examination of neural progenitor cells has failed to reveal a significant proximo-distal displacement of these cells through the enteric tube during development of the murine bowel, a defect in the migration of precursor cells down the alimentary tract to the terminal gut seems unlikely to be substantially involved in the pathogenesis of aganglionosis. This conclusion is supported by the normal enteric nervous system in proximal regions of the mutant gut and the presence of enteric type neurons outside of, but at the same level as the aganglionic region.     

Forebrain and lower brainstem participation in facilitatory and inhibitory regulation of the display of lordosis in female rats

Neural transection of the dorsal extrahypothalamic descending afferents by means of an L-shaped Halász knife at the anterior commissure (anterior roof deafferentation. ARD) markedly potentiated the display of lordosis and soliciting behaviors. Bilateral lesions of the ventromedial hypothalamus (VMH) attenuated lordotic activity in the ARD sham females but not in the ARD females. In contrast, the lesions in the pontine central gray concurrently with ARD effectively inhibited the display of lordosis but not soliciting behaviors. These results suggest that the VMH may not be a primary focus of the dorsal extrahypothalamic inhibitory influence on lordosis. The influence of this inhibitory system seems to be dominant in regulating the expression of lordosis behavior, compared to that of the hypothalamic lordosis facilitating system. Furthermore, the dorsal extrahypothalamic inhibitors influence which could be removed by ARD must be modified by the neural mechanism in the lower brain stem in which the pontine central gray may be actively involved.     

Peripheral lung carcinomas associated with central fibrosis and mixed small cell and other histologic components

Three cases of peripheral small cell lung carcinoma (SCLC) with central fibrosis are presented. Central fibrosis is usually present in adenocarcinomas. Cases 1 and 2 are combined SCLCs with components of papillary adenocar-cinoma, and case 3 is a mixed SCLC with a large cell component. Small cell Components showed intermediate cell type in ail cases. In cases 1 and 2, there was a gradual transition between small cell carcinoma and papillary ade-nocarcinoma. Small cell components showed Grimelius argyrophilia, but other neuroendocrine markers such as neuronspecific enorase, chromogranin A, Leu-7 and syn-aptophysln were negative. The chest X-ray examination of case 1 demonstrated rapid enlargement of a tumor shadow, which was present two years before, for a recent year. Central fibrosis, coexistence of small cell carcinoma and papillary adenocarcinoma, and a change of growth rate in the chest x-ray may suggest that some SCLC derive from papillary adenocarcinomas.     

NMDA receptor mediated dendritic plasticity in cortical cultures after oxygen-glucose deprivation

Dendrites and spines undergo dynamic changes in physiological and pathological conditions. Dendritic outgrowth has been observed in surviving neurons months after ischemia, which is associated with the functional compensation. It remains unclear how dendrites in surviving neurons are altered shortly after ischemia, which might reveal the mechanisms underlying neuronal survival. Using primary cortical cultures, we monitored the dendritic changes in individual neurons after oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately 30–50% cell death in 24 h. However, the total dendritic length in surviving neurons was significantly increased after OGD with a peak at 6 h after re-oxygenation. The increase of dendritic length after OGD was mainly due to the sprouting rather than the extension of the dendrites. The dendritic outgrowth after 2 h of OGD was greater than that after 4 h of OGD. Application of NMDA receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas application of AMPA receptor antagonist CNQX had no significant effects. These results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after OGD, which provides insights into the early response of surviving neurons after ischemia.     

A fluorescence histochemical and biochemical evaluation of the effect of p-chloroamphetamine on individual serotonergic nuclei in the rat brain.

The serotonin (5-hydroxytryptamine) content of eight raphe nuclei was measured 9 days after injection of p-chloroamphetamine. 5-Hydroxytryptamine levels were reduced in only the B-9 cell group.The histofluorescence of serotonergic neurons in the B-9 cell group was also studied at two time intervals after a single injection of p-chloroamphetamine. Nine days after the administration of p-chloroamphetamine there was a small decrease both in the intensity of fluorescence and in the number of yellow fluorescent serotonergic cells. After 2 months the drug caused a more marked decrease in the number of viable serotonergic cells. The results are discussed in relation to the mechanism of action of p-chloroamphetamine.It is suggested that following the administration of p-chloroamphetamine retrograde destruction may occur in the B-9 cell group, in contrast to those of the other raphe nuclei, whose cell bodies may possess a sufficient number of collateral processes to resist the slow neurotoxic destruction of their cell bodies.     

Preoptic area unit activity during sleep and wakefulness in the cat

The spontaneous discharge of 86 preoptic area (POA) neurons was recorded extracellularly in chronically prepared cats during wakefulness (W), slow-wave sleep (SWS), and REM sleep. Of these, the percentage of units exhibiting maximal discharge rates in SWS and REM sleep (84%) was significantly greater than that of those exhibiting a maximal discharge rate in W (16%). Furthermore, those neurons that discharged rapidly in sleep (fast units) generally had a reduced discharge rate in W. Sixteen of the 86 units showed a strong tendency to discharge in bursts during SWS but not during W or REM sleep. The mean coefficient of variation and the mean discharge rate for these bursting cells in SWS were significantly greater than the corresponding values for the same cells in W and REM sleep, and for the nonbursting cells in SWS. Because POA stimulation is known to initiate behavioral and electrocortical signs of sleep, it is suggested that "fast units" in SWS with reduced discharge rates in W, may be "hypnogenic" cells.     

褐云玛瑙螺中枢内支配大触角肌肉神经元的分布

实验用荧光素Ｂｂ逆行追踪方法，研究了褐云玛瑙螺支配大触角肌肉活动的神经元在中枢的分布，结果表明，Ｂｂ标记神经元大多分布于同侧脑节，少量分布于侧脑节，同侧口球节，足节和侧节，Ｂｂ标记神经元大多为中小型神经元，个别属于大型神经元。