Neuromodulator interactions and spinal cord injury in lamprey

Neuromodulation is mediated by neurotransmitters that typically act on G-protein-coupled receptors.It can confer behavioural flexibility by modifying the functional properties of anatomically hard-wired neural circuits.Single neuromodulators generally have divergent cellular and synaptic effects（Harris-Warrick and Johnson,2010）,and different modulators,

Phylogenetic analysis of 48 gene families revealing relationships between Hagfishes, Lampreys, and Gnathostomata

It has become clear that the extant vertebrates are divided into three major groups, that is, hagfishes, lampreys, and jawed vertebrates. Morphological and molecular studies, however, have resulted in conflicting views with regard to their interrelationships. To clarify the phylogenetic relationships between them, 48 orthologous protein-coding gene families were analyzed. Even as the analysis of 34 nuclear gene families supported the monophyly of cyclostomes, the analysis of 14 mitochondrial gene families suggested a closer relationship between lampreys and gnathostomes compared to hagfishes. Lampreys were sister group of gnathostomes. The results of this study supported the cyclostomes. Choice of outgroup, tree-making methods, and software may affect the phylogenetic prediction, which may have caused much debate over the subject. Development of new methods for tackling such problems is still necessary.

The functional properties of synapses made by regenerated axons across spinal cord lesion sites in lamprey

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively,little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals.This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey,a model system for spinal injury research,in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site.Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials.They also showed the same activity-dependent depression over spike trains.However,regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude.For axons above the lesion site,the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals.However,in this case,there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains.Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery.However,the postsynaptic input was maintained at the unlesioned level using different synaptic properties.Conversely,the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger.This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs.The animal experiments were approved by the Animal Ethics Committee of Cambridge University.

Lamprey： a model for vertebrate evolutionary research

Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research.

Cloning and identification of an Ubiquitinconjugating enzyme E2 D2 gene from Japanese lamprey Lampetra japonica

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2D2 gene.Here,we report a lamprey(La UBE2D2)gene which contained 441-bp open reading frame(ORF)encoding 147 amino acids with a typical UBC domain.Real-time PCR assay showed that the highest expression of the protein in adult lamprey was in the leukocytes,the lowest expression was in the skin,kidney and liver.The high conservation in amino acid sequence of the La UBE2D2protein with the UBE2D2s from Homo sapiens,Danio rerio,Oreochromis niloticus and Takifugu rubripes,implied that it had similar function with UBE2D2proteins from other species.

Role of axon resealing in retrograde neuronal death and regeneration after spinal cord injury

Spinal cord injury leads to persistent behavioral deficits because mammalian central nervous system axons fail to regenerate. A neuron's response to axon injury results from a complex interplay of neuron-intrinsic and environmental factors. The contribution of axotomy to the death of neurons in spinal cord injury is controversial because very remote axotomy is unlikely to result in neuronal death, whereas death of neurons near an injury may reflect environmental factors such as ischemia and inflammation. In lampreys, axotomy due to spinal cord injury results in delayed apoptosis of spinal-projecting neurons in the brain, beyond the extent of these environmental factors. This retrograde apoptosis correlates with delayed resealing of the axon, and can be reversed by inducing rapid membrane resealing with polyethylene glycol. Studies in mammals also suggest that polyethylene glycol may be neuroprotective, although the mechanism(s) remain unclear. This review examines the early, mechanical, responses to axon injury in both mammals and lampreys, and the potential of polyethylene glycol to reduce injury-induced pathology. Identifying the mechanisms underlying a neuron's response to axotomy will potentially reveal new therapeutic targets to enhance regeneration and functional recovery in humans with spinal cord injury.

Heterogeneity in the regenerative abilities of central nervous system axons within species: why do some neurons regenerate better than others?

Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is an emerging consensus that neurons have different intrinsic regenerative capabilities,which theoretically could be manipulated therapeutically to improve regeneration.Population-based comparisons between"good regenerating"and"bad regenerating"neurons in the CNS and peripheral nervous system of most vertebrates yield results that are inconclusive or difficult to interpret.At least in part,this reflects the great diversity of cells in the mammalian CNS.Using mammalian nervous system imposes several methodical limitations.First,the small sizes and large numbers of neurons in the CNS make it very difficult to distinguish regenerating neurons from non-regenerating ones.Second,the lack of identifiable neurons makes it impossible to correlate biochemical changes in a neuron with axonal damage of the same neuron,and therefore,to dissect the molecular mechanisms of regeneration on the level of single neurons.This review will survey the reported responses to axon injury and the determinants of axon regeneration,emphasizing non-mammalian model organisms,which are often under-utilized,but in which the data are especially easy to interpret.

A review of potential conservation and fisheries benefits of breaching four dams in the Lower Snake River(Washington,USA)

Abundances of important and imperiled fishes of the Snake River Basin continue to decline.We assessed the rationale for breaching the four lower Snake River Basin dams to prevent complete loss of these fishes,and to maximize their likelihood of recovery.We summarize the science surrounding Sockeye Salmon(Oncorhynchus nerka),Chinook Salmon(O.tshawytscha),steelhead(O.mykiss),Bull Trout(Salvelinus confluentus),White Sturgeon(Acipenser transmontanus),and Pacific Lamprey(Entosphenus tridentatus).From this,we drew ten conclusions:(1)development of the Columbia River System(including the Snake River Basin)has converted mainstem rivers into reservoirs,altering fish behavior and survival;(2)most populations currently record their lowest abundance;(3)the Columbia River System dams reduce productivity of diadromous fishes in the highest-quality spawning grounds that could buffer against future climate dynamics;(4)past actions have done little to reduce impacts or precipitate recovery;(5)the Columbia River System constrains survival and productivity of salmon,steelhead and Bull Trout;(6)Snake River Basin salmon and steelhead remain at high extinction risk;(7)eliminating migration impediments and improving mainstem habitats are essential for maintaining genetic diversity and improving Bull Trout persistence;(8)the lower Snake River Basin dams preclude passage of adult White Sturgeon,constraining gene flow and recruitment;(9)the lower Snake River Basin dams impede dramatically passage of adult and juvenile Pacific Lamprey,and(10)Snake River Basin Pacific Lamprey is at high risk of extirpation.Breaching the four lower Snake River Basin dams is an action likely to prevent extirpation and extinction of these fishes.Lessons from the Columbia River System can inform conservation in other impounded rivers.