大鼠前庭神经核群向腰髓投射特征——BDA法逆行研究

目的　研究大鼠前庭神经核群向脊髓的投射纤维特征。方法　在 7例SD大鼠采用结合生物素的葡聚糖胺(BDA)逆行法观察大鼠前庭核群向脊髓的投射。结果　除前庭神经上核 (SVN)外的其余各前庭核均有向大鼠腰髓的投射 ,单侧注射的实验动物中 ,前庭神经内侧核 (MVN)、外侧核 (LVN)和降核 (DVN)的标记神经元可见于双侧 ,其中MVN和LVN的标记神经元以注射同侧占优势 ,而DVN标记神经元两侧数量基本一致。结论　大鼠前庭脊髓尾侧束发出纤维投向脊髓腰段     

Brachydactyly type A3 is caused by a novel 13 bp HOXD13 frameshift deletion in a Chinese family

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1‐4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants of HOXD13 could be associated with BDA3 and BDA4. Here, we report a Chinese autosomal dominant BDA3 pedigree with a novel HOXD13 mutation. The affected individuals presented with an obviously shorter fifth middle phalanx. The radial side of the middle phalanx was shorter than the ulnar side, and the terminal phalanx of the fifth finger inclined radially and formed classical clinodactyly. Interestingly, the index finger was normal. The initial diagnosis was BDA3. However, the distal third and fourth middle phalanges were also slightly affected, resulting in mild radial clinodactyly. Both feet showed shortening of the middle phalanges, which were fused to the distal phalanges of the second to the fifth toes, as reported in BDA4. Therefore, this pedigree had combined BDA3 and atypical BDA4. By direct sequencing, a 13 bp deletion within exon 1 of HOXD13 (NM_000523.4: c.708_720del13; NP_000514.2: p.Gly237fs) was identified. The 13 bp deletion resulted in a frameshift and premature termination of HOXD13. This study provides further evidences that variants in HOXD13 cause BDA3‐BDA4 phenotypes.     

Sprouting and regeneration after pyramidotomy and blockade of the myelin-associated neurite growth inhibitors NI 35/250 in adult rats

After a selective unilateral lesion of the corticospinal tract (CST) at the level of the brainstem (pyramidotomy) and neutralization of the myelin associated neurite growth inhibitors NI-35/250 with the monoclonal antibody (mAb) IN-1, we had previously observed a strong behavioural recovery in parallel with an enhanced structural plasticity of the lesioned as well as the unlesioned CST. The present study focuses on the regenerative response of the cut CST axons at the lesion site in these adult rats. The results show a strong enhancement of regenerative sprouting of CST fibres by treatment with the mAb IN-1. Successful elongation of these sprouts through the pyramidal decussation and into the cervical spinal cord was also dependent on the presence of this antibody. In the spinal cord, regenerating fibres were rarely found in the position of the former CST; most of the fibres were distributed seemingly randomly over the entire lateral extent of the spinal cord.     

Thalamocortical and the dual pattern of corticothalamic projections of the posterior parietal cortex in macaque monkeys

The corticothalamic projection includes a main, modulatory projection from cortical layer VI terminating with small endings whereas a less numerous, driving projection from layer V forms giant endings. Such dual pattern of corticothalamic projections is well established in rodents and cats for many cortical areas. In non-human primates (monkeys), it has been reported for the primary sensory cortices (A1, V1, S1), the motor and premotor cortical areas and, in the parietal lobe, also for area 7. The present study aimed first at refining the cytoarchitecture parcellation of area 5 into the sub-areas PE and PEa and, second, establishing whether area 5 also exhibits this dual pattern of corticothalamic projection and what is its precise topography. To this aim, the tracer biotinylated dextran amine (BDA) was injected in area PE in one monkey and in area PEa in a second monkey. Area PE sends a major projection terminating with small endings to the thalamic lateral posterior nucleus (LP), ventral posterior lateral nucleus (VPL), medial pulvinar (PuM) and, but fewer, to ventral lateral posterior nucleus, dorsal division (VLpd), central lateral nucleus (CL) and center median nucleus (CM), whereas giant endings formed restricted terminal fields in LP, VPL and PuM. For area PEa, the corticothalamic projection formed by small endings was found mainly in LP, VPL, anterior pulvinar (PuA), lateral pulvinar (PuL), PuM and, to a lesser extent, in ventral posterior inferior nucleus (VPI), CL, mediodorsal nucleus (MD) and CM. Giant endings originating from area PEa formed restricted terminal fields in LP, VPL, PuA, PuM, MD and PuL. Furthermore, the origin of the thalamocortical projections to areas PE and PEa was established, exhibiting clusters of neurons in the same thalamic nuclei as above, in other words predominantly in the caudal thalamus. Via the giant endings CT projection, areas PE and PEa may send feedforward, transthalamic projections to remote cortical areas in the parietal, temporal and frontal lobes contributing to polysensory and sensorimotor integration, relevant for visual guidance of reaching movements for instance.     

Socio-economic Status and Membership of the British Diabetic Association in Scotland

Socio-economic status is an important predictor of mortality and morbidity in the diabetic and non-diabetic population. Improving the representation of people from deprived areas in vocal pressure groups may foster practical ideas which would improve health outcome. The general public may be represented through a variety of local and national organizations. The British Diabetic Association (BDA) represents people with diabetes mellitus, their relatives, and their health care professionals. Assuming a uniform diabetes prevalence of 1.5 %, there would be 75 484 diabetic people in Scotland, of which only 5649 (7.5 %) are currently members of the BDA. Using area based codes of socio-economic status, it was calculated that the odds ratios of BDA membership in the most affluent category (1) to the most deprived category (7) were 1.00, 0.81, 0.68, 0.57, 0.45, 0.43 and 0.21, respectively (p < 0.00001). Studies reporting on patient cohorts derived from the BDA membership files will include a higher proportion of patients from the most affluent categories, thus, these studies may underestimate overall morbidity and mortality. By promoting membership in the deprived categories it may be possible to develop a clearer picture of diabetes mellitus and new ideas which would help to narrow the health divide.     

生物素化葡聚糖胺逆行标记检测嗅鞘细胞移植对视神经损伤后视网膜神经节细胞存活的影响

目的通过生物素化葡聚糖胺(biopinylated dextan amine,BDA)逆行标记的方法,检测移植嗅鞘细胞对视神经损伤后视网膜神经节细胞(retinal ganglion cell,RGCs)存活的影响;观察BDA逆行标记RGCs效果。方法培养纯化嗅鞘细胞(olfactory ensheathing cells,OECs),并进行活性鉴定。取纯度为95%活性最高OECs种植于10只成年SD大鼠(雌雄不限)视神经吸断处,另设10只行单纯吸断伤作为对照,两组均于术后存活4W,做视网膜铺片,记数各象限同一视野下BDA荧光标记RGCs数。结果各视野下,移植OECs组荧光标记RGCs数均显著高于对照组(P<0.01);RGCs胞体及轴突轮廓清晰。结论OECs可有效保护RGCs,减缓其凋亡速率;BDA逆行标记RGCs效果理想,可进一步推广应用。     

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20 ms and 33 ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cells.     

Fiber connections of the diencephalic nucleus tuberis anterior in the weakly electric fish, Gymnotus cf. carapo: an in vivo tract-tracing study

Transport of biotinylated dextran amine shows the spatial segregation of mechanosensory afferents in the nucleus tuberis anterior (TA) of a gymnotiform fish, Gymnotus cf. carapo. Only the intermediate subdivision of this nucleus receives projections from the lateral region of the ventral torus semicircularis (TSv), which represents the principal midbrain center for mechanosensory information processing, and from the ventral nucleus praeeminentialis, which receives collaterals of ascending second order mechanosensory fibers that emerge from the mechanosensory lateral line lobe. Considering this aspect, a rostrocaudal subdivision of the TA is proposed. The TA also receives input from regions subserving other sensory modalities, suggesting a role in multisensory interaction. Another important finding of this work consisted in the demonstration of reciprocal connections between the TA and the inferior lobe of the hypothalamus, which is known to receive gustatory, visual, and electrosensory input and is therefore considered a multisensory integration center involved in feeding and aggressive behavior. Furthermore, reciprocal connections between the TA and the preelectromotor central-posterior/prepacemaker complex may provide an access for the processed mechanosensory information to interact with the transient modulations of the electric organ discharge that accompany different behaviors.     

Rehabilitative training following unilateral pyramidotomy in adult rats improves forelimb function in a non-task-specific way

Spontaneous functional recovery following injury to the adult central nervous system can be enhanced with increased and focused activity, either through altered behaviour (skill learning, exercise or training) or by artificial stimulation (magnetic or electrical). In terms of training, the choice of paradigm plays a key role in the recovered behaviour. Here we show that task-specific training leads to improved forelimb function that can be translated to a novel forelimb task. Adult Long–Evans rats received a unilateral pyramidotomy and we studied the effects of different post-lesion training paradigms for their ability to recover function in the impaired limb. We trained rats on either the single pellet grasping or the horizontal ladder task. Rats were tested on both tasks regardless of the training paradigm and also on a related, but novel forelimb task, the Staircase. Horizontal ladder training led to full recovery of this task, and also limited recovery on the familiar but untrained single pellet grasping task. In comparison, single pellet grasping training led to a smaller improvement on the horizontal ladder, but interestingly the same degree of recovery on the single pellet grasping task as horizontal ladder trained animals. Both training groups performed equally well on a novel, untrained forelimb grasping task. These results show that task-specific forelimb training can lead to functional recovery also in non-trained, complex, forelimb movements. Anatomically, only single pellet grasping training was associated with enhanced sprouting of the intact corticospinal tract across the cervical spinal cord midline to innervate the denervated side of the spinal cord.