Somatotopy of digital nerve projections to the dorsal horn in the monkey

The dorsal horn projection patterns of finger nerves were investigated in four Macaca mulatta monkeys. Proper digital branches of the median nerves, serving the radial aspect of a digit on each hand, were loaded with wheatgerm agglutinin-horseradish peroxidase complex (WGA:HRP). The distribution of the lectin-enzyme complex was mapped in the right and left dorsal horns. The dorsal horn projections of the digital nerves were localized in segments C6-C8 in laminae I-VI, primarily in laminae I-IV. The wedge-shaped termination zones were somatotopically organized, in agreement with the projections of the digits in cats. The fingers are represented medially, as they are in the cat. This similarity suggests that there is a mediolateral gradient of dorsal horn organization similar to that of the cat, with distal skin represented medially and proximal skin represented laterally. The rostrocaudal trajectory of finger representation, with digit 1 most rostral and digit 5 most caudal, is also in agreement with the organization of hindlimb toe projections in the cat. There was a high degree of bilateral symmetry for homologous nerves, and little overlap of projections from nerves innervating adjacent fingers. The sample size was too small to permit us to assess interanimal variation. These results suggest a similar somatotopy of projections, and presumably of dorsal horn cell somatotopy, in monkey and cat.     

Extra-lemniscal afferent projections of dorsal spinal cord nuclei to the ventrobasal nuclear complex structure in the contralateral optic thalamus

It has been found that section of half the midbrain tegmentum in cats failed to prevent the afferent somatosensory projections from the foreleg to the ventrobasal nuclear complex of the contralateral thalamus. Specific evoked responses to the stimulation of the contralateral foreleg were recorded in this structure. These specific EP have the same latency as "lemniscal responses" (4-5 ms) and diminish the amplitude and duration of both components of the responses. Simultaneously, we have observed terminal axonal degeneration into the ventrobasal nuclear complex of the thalamus 5-7 days after the section of the contralateral midbrain tegmentum, using the electron microscopy method. All the results obtained indicate that the dorsal column nuclei have extra-lemniscal afferent connections with ventrolateral nuclear complex of the contralateral thalamus. These connections ascend in the back parts of the brainstem ipsilaterally to the corresponding pair of the dorsal column nuclei and rostrally to the midbrain on the contralateral side.     

BMP ligands act redundantly to pattern the dorsal telencephalic midline

The embryonic telencephalon is patterned into several areas that give rise to functionally distinct structures in the adult forebrain. Previous studies have shown that BMP4 and BMP2 can induce features characteristic of the telencephalic midline in cultured explants, suggesting that the normal role of BMP4 in the forebrain is to pattern the medial lateral axis of the telencephalon by promoting midline cell fates. To test this hypothesis directly in vivo, the Bmp4 gene was efficiently disrupted in the telencephalon using a CRE/loxP approach. Analysis of Bmp4-deficient telencephalons fails to reveal a defect in patterning, cell proliferation, differentiation, or apoptosis. The absence of a phenotype in the Bmp4-deficient telencephalon along with recent genetic studies establishing a role for a BMP4 receptor, BMPRIA, in telencephalic midline development, demonstrate that loss of Bmp4 function in the telencephalon can be compensated for by at least one other Bmp gene, the identity of which has not yet been determined.     

BMP signaling is required locally to pattern the dorsal telencephalic midline

BMPs have been proposed to pattern the medial-lateral axis of the telencephalon in a concentration-dependent manner, thus helping to subdivide the embryonic telencephalon into distinct forebrain regions. Using a CRE/loxP genetic approach, we tested this hypothesis by disrupting the Bmpr1a gene in the telencephalon. In mutants, BMP signaling was compromised throughout the dorsal telencephalon, but only the most dorsalmedial derivative, the choroid plexus, failed to be specified or differentiate. Choroid plexus precursors remained proliferative and did not adopt the fate of their lateral telencephalic neighbors. These results demonstrate that BMP signaling is required for the formation of the most dorsal telencephalic derivative, the choroid plexus, and that BMP signaling plays an essential role in locally patterning the dorsal midline. Our data fail to support a more global, concentration-dependent role in specifying telencephalic cell fates.     

去甲肾上腺素在脊髓背角的镇痛机制

疹髓背角浅层是传递和调制外周伤害性信息的关键部位。起源于脑干的去甲肾上腺素（NA）能纤维终止脊髓背角,它们释放的NA具有抑制初级传入末梢释放谷氨酸和P物质、增加Ⅱ层（胶状质）抑制性神经活性物质释放的作用。此外,形态学研究提示NA可能直接抑制Ⅰ/Ⅲ层向丘脑传递伤害性信息的投射神经元。NA可能通过以上途径,实现对外周伤害性信息传递的调制而发挥镇痛作用。     

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region.     

Abnormal physiology of the dorsal horn as related to the deafferentation syndrome

The spinal cord dorsal horn has been implicated in the generation of pain and dysesthesias following nerve and nerve root damage and/or avulsion, as well as following damage in adjacent spinal cord regions. Alterations in the functional properties of dorsal horn neurons occur after deafferentation and may underlie the occurrence of abnormal sensations referred to the denervated body part. Abnormal activity following deafferentation has also been noted at thalamic and cortical levels. Some of these post-denervation functional changes, determined anatomically and/or electrophysiologically, are reviewed as well as the results of behavioral studies of the deafferentation syndrome in the rat.     

Characteristics of dorsal horn neurons expressing subliminal responses to sural nerve stimulation

The present study was designed (1) to characterize the subliminal responses of dorsal horn neurons to stimulation of the sural nerve, and (2) to correlate the type of response to this stimulus with the responses to natural mechanical stimulation of the skin. To accomplish this, intracellular and extracellular recordings were carried out in L6 and L7 dorsal horn neurons in the cat. The excitatory responses of each cell to electrical stimulation of the sural nerve and to mechanical stimulation of the skin were noted. Of 35 dorsal horn cells recorded intracellularly, 11 responded with impulses to sural nerve stimulation, 9 responded with excitatory postsynaptic potentials (EPSPs) but not impulses, and 15 had no excitatory responses to this stimulus. The type of response to sural nerve stimulation was strongly correlated with receptive field modality. Most cells receiving an input from high-threshold cutaneous mechanoreceptors responded with impulses or gave no excitatory response to sural nerve stimulation, whereas most cells that had only low-threshold mechanoreceptor input responded with EPSPs only or gave no response. In cells with only low-threshold (LT) mechanoreceptive input, response to sural nerve stimulation was highly correlated with receptive field locus. Those LT cells with no excitatory responses to sural nerve stimulation had receptive fields confined to the foot and/or toes, whereas those that gave EPSPs had more proximal receptive fields. The possible significance of these data with reference to changes observed after lesions, such as increased response to sural nerve stimulation, increased receptive field size, and somatotopic reorganization, is discussed.     

Progenitor cells of the rod-free area centralis originate in the anterior dorsal optic vesicle

Background  

Nervous system development is dependent on early regional specification to create functionally distinct tissues within an initially undifferentiated zone. Within the retina, photoreceptors are topographically organized with rod free area centrales faithfully generated at the centre of gaze. How does the developing eye regulate this placement? Conventional wisdom indicates that the distal tip of the growing optic vesicle (OV) gives rise to the area centralis/fovea. Ectopic expression and ablation studies do not fully support this view, creating a controversy as to the origin of this region. In this study, the lineage of cells in the chicken OV was traced using DiI. The location of labelled cells was mapped onto the retina in relation to the rod-free zone at embryonic (E) 7 and E17.5. The ability to regenerate a rod free area after OV ablation was determined in conjunction with lineage tracing.     

Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow

Myofibroblasts play a key role in wound closure but their origin is poorly understood. To investigate whether fibrocytes contribute to myofibroblast population, we examined the phenotype of fibrocytes and myofibroblasts present in the wounded skin of BALB/c mice. During wound healing, there was a marked increase in the number of cells expressing the myofibroblast marker alpha-smooth muscle actin in the granulation tissue. Between 4 and 7 days post-wounding, more than 50% of these cells also expressed the CD13 antigen. CD13(+)/collagen I+ fibrocytes could be isolated at an early stage of the healing process from digested fragments of wounded tissue by fluorescence-activated cell sorting. Like authentic fibrocytes, these cells were also CD45(+)/CD34(+)/CD14-. Between 4 and 7 days post-injury, 61.4% of the isolated fibrocytes were found to express alpha-smooth muscle actin gene and protein. We repeated similar experiments in female mice that had received a male whole bone marrow transplant after total body irradiation. By in situ hybridization, we identified the Y chromosome in the nuclei of the majority of fibrocytes isolated from the wounded tissue of these animals. Our data indicate that circulating fibrocytes contribute to the myofibroblast population in the wounded skin and that they originate from the bone marrow.     

P2X receptor-mediated purinergic sensory pathways to the spinal cord dorsal horn

P2X receptors are expressed on different functional groups of primary afferent fibers. P2X receptor-mediated sensory inputs can be either innocuous or nociceptive, depending on which dorsal horn regions receive these inputs. We provide a brief review of P2X receptor-mediated purinergic sensory pathways to different regions in the dorsal horn. These P2X purinergic pathways are identified in normal animals, which provides insights into their physiological functions. Future studies on P2X purinergic pathways in animal models of pathological conditions may provide insights on how P2X receptors play a role in pathological pain states.     

Chronic pregabalin inhibits synaptic transmission between rat dorsal root ganglion and dorsal horn neurons in culture

In this study, we have examined the properties of synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons, placed in co-culture. We also examined the effect of the anti-hyperalgesic gabapentinoid drug pregabalin (PGB) at this pharmacologically relevant synapse. The main method used was electrophysiological recording of excitatory post synaptic currents (EPSCs) in DH neurons. Synaptic transmission between DRG and DH neurons was stimulated by capsaicin, which activates transient receptor potential vanilloid-1 (TRPV1) receptors on small diameter DRG neurons. Capsaicin (1 μM) application increased the frequency of EPSCs recorded in DH neurons in DRG-DH co-cultures, by about 3-fold, but had no effect on other measured properties of the EPSCs. There was also no effect of capsaicin in the absence of co-cultured DRGs. Application of PGB (100 μM) for 40–48 h caused a reduction in the capsaicin-induced increase in EPSC frequency by 57%. In contrast, brief preincubation of PGB had no significant effect on the capsaicin-induced increase in EPSC frequency. In conclusion, this study shows that PGB applied for 40–48 h, but not acute application inhibits excitatory synaptic transmission at DRG-DH synapses, in response to nociceptive stimulation, most likely by a presynaptic effect on neurotransmitter release from DRG presynaptic terminals.     

Chronic pregabalin inhibits synaptic transmission between rat dorsal root ganglion and dorsal horn neurons in culture

In this study, we have examined the properties of synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons, placed in co-culture. We also examined the effect of the anti-hyperalgesic gabapentinoid drug pregabalin (PGB) at this pharmacologically relevant synapse. The main method used was electrophysiological recording of excitatory post synaptic currents (EPSCs) in DH neurons. Synaptic transmission between DRG and DH neurons was stimulated by capsaicin, which activates transient receptor potential vanilloid-1 (TRPV1) receptors on small diameter DRG neurons. Capsaicin (1 μM) application increased the frequency of EPSCs recorded in DH neurons in DRG-DH co-cultures, by about 3-fold, but had no effect on other measured properties of the EPSCs. There was also no effect of capsaicin in the absence of co-cultured DRGs. Application of PGB (100 μM) for 40-48 h caused a reduction in the capsaicin-induced increase in EPSC frequency by 57%. In contrast, brief preincubation of PGB had no significant effect on the capsaicin-induced increase in EPSC frequency. In conclusion, this study shows that PGB applied for 40-48 h, but not acute application inhibits excitatory synaptic transmission at DRG-DH synapses, in response to nociceptive stimulation, most likely by a presynaptic effect on neurotransmitter release from DRG presynaptic terminals.     

Identification of the Ruffini corpuscle in human hairy skin

Summary A Ruffini corpuscle was identified in the dense reticular dermis of the human scalp from a patient with alopecia areata. The corpuscle measured approximately 50 m in diameter. One afferent myelinated axon with a diameter of 4–6 m supplies the corpuscle. Branched axon terminals and the associated Schwann cells tightly envelop parallel bundles of collagen fibrils. Axon terminals evidenced focal swellings, and small finger-like protrusions projected into the endoneural connective tissue. The terminals are characterized by the presence of abundant mitochondria, numerous vesicles, particles of glycogen and electron-opaque lipid material. A thin perineural capsule envelops the bundles of collagen fibrils and associated terminals. The present study provides the first electron-microscopic characterization of a Ruffini corpuscle in human hairy skin.This study was supported in part by the Deutsche ForschungsgemeinschaftSupported in part by U.S. Public Health Service Research Contracts NIDR72-2401 and HD4-2869 and Research Grant HD 11216