Selective plasticity of layer 2/3 inputs onto distal forelimb controlling layer 5 corticospinal neurons with skilled grasp motor training.

Layer 5 neurons of the neocortex receive their principal inputs from layer 2/3 neurons. We seek to identify the nature and extent of the plasticity of these projections with motor learning. Using optogenetic and viral intersectional tools to selectively stimulate distinct neuronal subsets in rat primary motor cortex, we simultaneously record from pairs of corticospinal neurons associated with distinct features of motor output control: distal forelimb vs. proximal forelimb. Activation of Channelrhodopsin2-expressing layer 2/3 afferents onto layer 5 in untrained animals produces greater monosynaptic excitation of neurons controlling the proximal forelimb. Following skilled grasp training, layer 2/3 inputs onto corticospinal neurons controlling the distal forelimb associated with skilled grasping become significantly stronger. Moreover, peak excitatory response amplitude nearly doubles while latency shortens, and excitatory-to-inhibitory latencies become significantly prolonged. These findings demonstrate distinct, highly segregated, and cell-specific plasticity of layer 2/3 projections during skilled grasp motor learning.

Relationship between the Residual Cesium Body Contents and Individual Behaviors among Evacuees from Municipalities near the Fukushima Daiichi Nuclear Power Plant.

ABSTRACT: To support estimations of early individual internal doses to residents who suffered from the 2011 accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), we have sought to use whole-body counter (WBC) measurement results of subjects who lived in municipalities neighboring the FDNPP at the time of the accident. These WBC measurements started several months after the accident; the targeted radionuclides were 134Cs and 137Cs. Our previous study had analyzed the relationship between the residual Cs contents of individuals and evacuation behaviors in the period immediately after the accident for residents of Namie-town, one of the most radiologically affected municipalities. Those results suggested that the first major release event at the FDNPP on 12 March 2011 caused significant exposure, particularly to those who delayed evacuation on that day. The present study expanded its scope to include subjects from four towns neighboring the FDNPP (Namie, Futaba, Okuma, and Tomioka) to gather additional evidence of the exposure that took place on 12 March 2011. Additionally, we investigated the relationship between individual cesium doses and subjects' destinations following the largest release event on 15 March 2011. The study population was 1,145 adults. We first divided the subjects into two evacuation groups depending on the distance from the FDNPP and their evacuation whereabouts (25-km boundary) as of 15:00 on 12 March 2011: the G1 group (≥25 km) and the G2 group (<25 km). We further divided these two subject groups into seven subgroups based on the subjects' destinations as of 0:00 on 16 March 2011. Our four main findings are as follows. (1) The 137Cs detection rate was significantly different between the G1 and G2 groups of Namie-town and Futaba-town but not for those of Okuma-town and Tomioka-town. This result corresponds to the plume passage (flowing toward the northwest to the north) in the afternoon of 12 March 2011 and supports our previous study. (2) The upper-percentile committed effective doses (CEDs) of the G2 groups were higher than those of the G1 groups for all four towns, although the between-group difference varied with the town. The highest CEDs were found in the G2 group of Futaba-town, and the lowest CEDs were in the Namie-town G1 group: 0.16 mSv and 0.04 mSv at the 90th percentile, respectively. The CEDs for both the G1 and G2 groups were relatively high for Okuma-town and Tomioka-town compared to those of the G1 group of Namie-town, although the former subjects were expected to be less exposed on 12 March 2011 and then evacuated to remote places, as did the residents of the other towns. (3) The CEDs of the G1 subgroup that evacuated outside Fukushima Prefecture were extremely low, suggesting that these subjects were little exposed on both 12 and 15 March 2011. However, the CEDs of the same G1 subgroup were rather higher than those of the corresponding G2 subgroup for Futaba-town and Okuma-town. We thus speculate that the WBC measurements were likely to have been affected by the contamination occurring in the second-round temporary re-entry (except for the Namie-town residents). (4) The analyses of the Namie-town evacuees indicated that the area including the middle and northern parts of Fukushima Prefecture was relatively more affected by the major release event on 15 March 2011. In conclusion, the early cesium intake due to the FDNPP accident remained detectable in the WBC measurements of certain present subjects; however, further analyses of the available data are necessary for a full understanding of the WBC measurement results.

Screening levels of TCS-172 NaI(Tl) survey meters used for direct thyroid measurements in nuclear disasters.

It is a challenging task to establish a feasible and robust method for the population monitoring of individuals' thyroid exposure following an accidental intake of radioiodines in a nuclear emergency, because of the time restriction. The authors previously proposed a method for such monitoring to obtain as many reliable human data as possible and one of the components is simplified measurements by conventional NaI(Tl) survey meters that are intended to be used for the initial triage to identify significantly exposed individuals and get an overall picture of the exposure levels in a target population in a timely manner. This study determined screening levels (SLs) for a conventional NaI(Tl) survey meter (model TCS-172, Hitachi, Japan) using the conversion factor (131I kBq in the thyroid per µSv h-1) that were obtained from experiments and simulations with age-specific phantoms. The results demonstrated that the derived SLs for 100 mSv thyroid equivalent dose were as follows: 0.2 µSv h-1 (SL1) for the age group ≤ 5-y-olds, 0.5 µSv h-1 (SL2) for the 10- and 15-y-old age groups and 1.0 µSv h-1 (SL3) for adults. These SLs would be reasonably available within 1 week after the intake of 131I on the safe side.

A preliminary report on retrospective dose assessment by FISH translocation assay in FDNPP Nuclear Emergency Worker Study (NEWS).

In Japan, a national project of longitudinal health care and epidemiological research (NEWS) was developed in 2014 to analyse the effects of radiation on human health for workers who responded to the Fukushima Dai-ichi nuclear emergency in 2011. In 2018, peripheral blood for chromosome translocation analysis was collected from 62 workers. Retrospective dose assessment was performed with fluorescence in situ hybridisation translocation (FISH-Tr) assay. The range of estimated doses by FISH-Tr assay was 0-635 mGy, in which 22 workers had estimated doses of more than 189 mGy. Biological dose estimates were five times higher in workers with physically measured total exposure recordings above 70 mGy. It is likely that smoking and medical exposure caused the discrepancy between estimated biological and physical total exposure doses. Thus, there is a possibility that retrospective biodosimetry assessment might over-estimate occupational exposures to workers exposed to chronic radiation during nuclear emergency work.

Fact-finding survey on the competencies and literacy of radiological technologists regarding radiation disasters.

BACKGROUND: Radiological technologists serve as risk communicators who aim to lessen patients' anxiety about radiation exposure, in addition to performing radiological examinations. OBJECTIVE: We conducted a fact-finding survey on knowledge and awareness of radiation disasters among the radiological technologists to reveal their literacy and competencies regarding radiation disasters. METHODS: A paper questionnaire was distributed to 1,835 radiological technologists at 166 National Hospital Organization facilities in Japan. The 28-item questionnaire covered knowledge and awareness of radiation protection and radiation disasters. Radiological technologists were divided into 2 groups by regionality: areas where a nuclear power station was present/nearby (NPS areas) and non-NPS areas. RESULTS: Completed questionnaires were returned from 148 facilities with a facility response rate of 89.2% and from 1,391 radiological technologists with a response rate of 75.8%. There were 1,290 valid responses with a valid response rate of 70.3%. The correct answer rate for knowledge of radiation protection and radiation disasters was high in the 24 NPS areas. There were no differences in awareness of radiation disasters between NPS and non-NPS areas. CONCLUSIONS: Establishing a nationwide, region-independent training system can be expected to improve literacy regarding radiation disasters among radiological technologists. Willingness to assist during disasters was high among radiological technologists irrespective of area, indicating that the competencies of radiological technologists represent a competency model for radiation disaster assistance.

Rhesus macaque versus rat divergence in the corticospinal projectome.

We used viral intersectional tools to map the entire projectome of corticospinal neurons associated with fine distal forelimb control in Fischer 344 rats and rhesus macaques. In rats, we found an extraordinarily diverse set of collateral projections from corticospinal neurons to 23 different brain and spinal regions. Remarkably, the vast weighting of this "motor" projection was to sensory systems in both the brain and spinal cord, confirmed by optogenetic and transsynaptic viral intersectional tools. In contrast, rhesus macaques exhibited far heavier and narrower weighting of corticospinal outputs toward spinal and brainstem motor systems. Thus, corticospinal systems in macaques primarily constitute a final output system for fine motor control, whereas this projection in rats exerts a multi-modal integrative role that accesses far broader CNS regions. Unique structural-functional correlations can be achieved by mapping and quantifying a single neuronal system's total axonal output and its relative weighting across CNS targets.

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury.

Neural stem/progenitor cell (NSPC) grafts can integrate into sites of spinal cord injury (SCI) and generate neuronal relays across lesions that can provide functional benefit. To determine if and how grafts become synaptically organized and connect with host systems, we performed calcium imaging of NSPC grafts in SCI sites in vivo and in adult spinal cord slices. NSPC grafts organize into localized and spontaneously active synaptic networks. Optogenetic stimulation of host corticospinal tract axons regenerating into grafts elicited distinct and segregated neuronal network responses throughout the graft. Moreover, optogenetic stimulation of graft-derived axons extending from the graft into the denervated spinal cord also triggered local host neuronal network responses. In vivo imaging revealed that behavioral stimulation likewise elicited focal synaptic responses within grafts. Thus neural progenitor grafts can form functional synaptic subnetworks whose activity patterns resemble intact spinal cord.

Correction to: Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking.

The author reports that data for electrophysiology findings reported in Figs. 4 and 5 for control group and Meth Rst group have been published previously (Galinato MH et al., J Neurosci. 2018 Feb 21; 38(8):2029-2042.

Reorganization of Recurrent Layer 5 Corticospinal Networks Following Adult Motor Training.

Recurrent synaptic connections between neighboring neurons are a key feature of mammalian cortex, accounting for the vast majority of cortical inputs. Although computational models indicate that reorganization of recurrent connectivity is a primary driver of experience-dependent cortical tuning, the true biological features of recurrent network plasticity are not well identified. Indeed, whether rewiring of connections between cortical neurons occurs during behavioral training, as is widely predicted, remains unknown. Here, we probe M1 recurrent circuits following motor training in adult male rats and find robust synaptic reorganization among functionally related layer 5 neurons, resulting in a 2.5-fold increase in recurrent connection probability. This reorganization is specific to the neuronal subpopulation most relevant for executing the trained motor skill, and behavioral performance was impaired following targeted molecular inhibition of this subpopulation. In contrast, recurrent connectivity is unaffected among neighboring layer 5 neurons largely unrelated to the trained behavior. Training-related corticospinal cells also express increased excitability following training. These findings establish the presence of selective modifications in recurrent cortical networks in adulthood following training.SIGNIFICANCE STATEMENT Recurrent synaptic connections between neighboring neurons are characteristic of cortical architecture, and modifications to these circuits are thought to underlie in part learning in the adult brain. We now show that there are robust changes in recurrent connections in the rat motor cortex upon training on a novel motor task. Motor training results in a 2.5-fold increase in recurrent connectivity, but only within the neuronal subpopulation most relevant for executing the new motor behavior; recurrent connectivity is unaffected among adjoining neurons that do not execute the trained behavior. These findings demonstrate selective reorganization of recurrent synaptic connections in the adult neocortex following novel motor experience, and illuminate fundamental properties of cortical function and plasticity.

Sex Differences in Context-Driven Reinstatement of Methamphetamine Seeking is Associated with Distinct Neuroadaptations in the Dentate Gyrus.

The present study examined differences in operant responses in adult male and female rats during distinct phases of addiction. Males and females demonstrated escalation in methamphetamine (0.05 mg/kg, i.v.) intake with females showing enhanced latency to escalate, and bingeing. Following protracted abstinence, females show reduced responses during extinction, and have greater latency to extinguish compared with males, indicating reduced craving. Females demonstrated lower context-driven reinstatement compared to males, indicating that females have less motivational significance to the context associated with methamphetamine. Whole-cell patch-clamp recordings on dentate gyrus (DG) granule cell neurons (GCNs) were performed in acute brain slices from controls and methamphetamine experienced male and female rats, and neuronal excitability was evaluated from GCNs. Reinstatement of methamphetamine seeking reduced spiking in males, and increased spiking in females compared to controls, demonstrating distinct neuroadaptations in intrinsic excitability of GCNs in males and females. Reduced excitability of GCNs in males was associated with enhanced levels of neural progenitor cells, expression of plasticity-related proteins including CaMKII, and choline acetyltransferase in the DG. Enhanced excitability in females was associated with an increased GluN2A/2B ratio, indicating changes in postsynaptic GluN subunit composition in the DG. Altered intrinsic excitability of GCNs was associated with reduced mossy fiber terminals in the hilus and pyramidal projections, demonstrating compromised neuroplasticity in the DG in both sexes. The alterations in excitability, plasticity-related proteins, and mossy fiber density were correlated with enhanced activation of microglial cells in the hilus, indicating neuroimmune responses in both sexes. Together, the present results indicate sexually dimorphic adaptive biochemical changes in excitatory neurotransmitter systems in the DG and highlight the importance of including sex as a biological variable in exploring neuroplasticity and neuroimmune changes that predict enhanced relapse to methamphetamine-seeking behaviors.

The role of hippocampal adult neurogenesis in methamphetamine addiction.

One of the consequences of chronic methamphetamine (Meth) abuse and Meth addiction is impaired hippocampal function which plays a critical role in enhanced propensity for relapse. This impairment is predicted by alterations in hippocampal neurogenesis, structural- and functional-plasticity of granule cell neurons (GCNs), and expression of plasticity-related proteins in the dentate gyrus. This review will elaborate on the effects of Meth in animal models during different stages of addiction-like behavior on proliferation, differentiation, maturation, and survival of newly born neural progenitor cells. We will then discuss evidence for the contribution of adult neurogenesis in context-driven Meth-seeking behavior in animal models. These findings from interdisciplinary studies suggest that a subset of newly born GCNs contribute to context-driven Meth-seeking in Meth addicted animals.

Generation and post-injury integration of human spinal cord neural stem cells.

Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for 'replacement' strategies in several spinal cord disorders.

New Neurons in the Dentate Gyrus Promote Reinstatement of Methamphetamine Seeking.

Addictive drugs effect the brain reward circuitry by altering functional plasticity of neurons governing the circuits. Relapse is an inherent problem in addicted subjects and is associated with neuroplasticity changes in several brain regions including the hippocampus. Recent studies have begun to determine the functional significance of adult neurogenesis in the dentate gyrus of the hippocampus, where new neurons in the granule cell layer are continuously generated to replace dying or diseased cells. One of the many negative consequences of chronic methamphetamine (METH) abuse and METH addiction in rodent and nonhuman primate models is a decrease in neural progenitor cells in the dentate gyrus and reduced neurogenesis in the granule cell layer during METH exposure. However, the number of progenitors rebound during withdrawal and abstinence from METH and the functional significance of enhanced survival of the progenitors during abstinence on the propensity for relapse was recently investigated by Galinato et al. A rat model of METH addiction in concert with a pharmacogenetic approach of ablating neural progenitor cells revealed that neurogenesis during abstinence promoted a relapse to METH-seeking behavior. Biochemical and electrophysiology studies demonstrated that an increase in neurogenesis during abstinence correlated with increases in plasticity-related proteins associated with learning and memory in the dentate gyrus and enhanced spontaneous activity and reduced neuronal excitability of granule cell neurons. Based on these findings, we discuss the putative molecular mechanisms that could drive aberrant neurogenesis during abstinence. We also indicate forebrain-dentate gyrus circuits that could assist with aberrant neurogenesis and drive a relapse into METH-seeking behavior in METH-addicted animals.

TrpM8-mediated somatosensation in mouse neocortex.

Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well-defined somatosensory modality, cool sensation mediated by peripheral TrpM8-receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor-expressing neurons, we identify candidate neocortical areas responsive for cool sensation. Initially, we optimized TrpM8 stimulation and determined that menthol, a selective TrpM8 agonist, was more effective than cool stimulation at inducing expression of the immediate-early gene c-fos in the spinal cord. We developed a broad-scale brain survey method for identification of activated brain areas, using automated methods to quantify c-fos immunoreactivity (fos-IR) across animals. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos-IR after menthol stimulation, in contrast to weaker activation in primary somatosensory cortex (S1). In addition, menthol exposure triggered fos-IR in piriform cortex, the amygdala, and the hypothalamus. Menthol-mediated activation was absent in TrpM8-knock-out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1. These findings are consistent with data from humans indicating that the posterior insula is specialized for somatosensory information encoding temperature, pain, and gentle touch.

Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking.

Abstinence from unregulated methamphetamine self-administration increases hippocampal dependent, context-driven reinstatement of methamphetamine seeking. The current study tested the hypothesis that alterations in the functional properties of granule cell neurons (GCNs) in the dentate gyrus (DG) of the hippocampus in concert with altered expression of synaptic plasticity-related proteins and ultrastructural changes in the DG are associated with enhanced context-driven methamphetamine-seeking behavior. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naïve (controls) and methamphetamine experienced animals (during acute withdrawal, during abstinence, after extinction and after reinstatement). Spontaneous excitatory postsynaptic currents (sEPSCs) and intrinsic excitability were recorded from GCNs. Reinstatement of methamphetamine seeking increased sEPSC frequency and produced larger amplitude responses in GCNs compared to controls and all other groups. Reinstatement of methamphetamine seeking reduced spiking capability in GCNs compared to controls, and all other groups, as indicated by reduced intrinsic spiking elicited by increasing current injections, membrane resistance and fast after hyperpolarization. In rats that reinstated methamphetamine seeking, these altered electrophysiological properties of GCNs were associated with enhanced expression of Fos, GluN2A subunits and PSD95 and reduced expression of GABAA subunits in the DG and enhanced expression of synaptic PSD in the molecular layer. The alterations in functional properties of GCNs and plasticity related proteins in the DG paralleled with no changes in structure of microglial cells in the DG. Taken together, our results demonstrate that enhanced reinstatement of methamphetamine seeking results in alterations in intrinsic spiking and spontaneous glutamatergic synaptic transmission in the GCNs and concomitant increases in neuronal activation of GCNs, and expression of GluNs and decreases in GABAA subunits that may contribute to the altered synaptic connectivity-neuronal circuitry-and activity in the hippocampus, and enhance propensity for relapse.

Neurogenesis during Abstinence Is Necessary for Context-Driven Methamphetamine-Related Memory.

Abstinence from methamphetamine addiction enhances proliferation and differentiation of neural progenitors and increases adult neurogenesis in the dentate gyrus (DG). We hypothesized that neurogenesis during abstinence contributes to context-driven drug-seeking behaviors. To test this hypothesis, the pharmacogenetic rat model (GFAP-TK rats) was used to conditionally and specifically ablate neurogenesis in the DG. Male GFAP-TK rats were trained to self-administer methamphetamine or sucrose and were administered the antiviral drug valganciclovir (Valcyte) to produce apoptosis of actively dividing GFAP type 1 stem-like cells to inhibit neurogenesis during abstinence. Hippocampus tissue was stained for Ki-67, NeuroD, and DCX to measure levels of neural progenitors and immature neurons, and was stained for synaptoporin to determine alterations in mossy fiber tracts. DG-enriched tissue punches were probed for CaMKII to measure alterations in plasticity-related proteins. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naive (controls) and methamphetamine experienced animals (+/-Valcyte). Spontaneous EPSCs and intrinsic excitability were recorded from granule cell neurons (GCNs). Reinstatement of methamphetamine seeking enhanced autophosphorylation of CaMKII, reduced mossy fiber density, and induced hyperexcitability of GCNs. Inhibition of neurogenesis during abstinence prevented context-driven methamphetamine seeking, and these effects correlated with reduced autophosphorylation of CaMKII, increased mossy fiber density, and reduced the excitability of GCNs. Context-driven sucrose seeking was unaffected. Together, the loss-of-neurogenesis data demonstrate that neurogenesis during abstinence assists with methamphetamine context-driven memory in rats, and that neurogenesis during abstinence is essential for the expression of synaptic proteins and plasticity promoting context-driven drug memory.SIGNIFICANCE STATEMENT Our work uncovers a mechanistic relationship between neurogenesis in the dentate gyrus and drug seeking. We report that the suppression of excessive neurogenesis during abstinence from methamphetamine addiction by a confirmed phamacogenetic approach blocked context-driven methamphetamine reinstatement and prevented maladaptive changes in expression and activation of synaptic proteins and basal synaptic function associated with learning and memory in the dentate gyrus. Our study is the first to demonstrate an interesting and dysfunctional role of adult hippocampal neurogenesis during abstinence to drug-seeking behavior in animals self-administering escalating amounts of methamphetamine. Together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.

Low 134Cs/137Cs ratio anomaly in the north-northwest direction from the Fukushima Dai-ichi Nuclear Power Station.

A low 134Cs/137Cs ratio anomaly in the north-northwest (NNW) direction from the Fukushima Dai-ichi Nuclear Power Station (FDNPS) is identified by a new analysis of the 134Cs/137Cs ratio dataset which we had obtained in 2011-2015 by a series of car-borne surveys that employed a germanium gamma-ray spectrometer. We found that the 134Cs/137Cs ratio is slightly lower (0.95, decay-corrected to March 11, 2011) in an area with a length of about 15 km and a width of about 3 km in the NNW direction from the FDNPS than in other directions from the station. Furthermore, the area of this lower 134Cs/137Cs ratio anomaly corresponds to a narrow contamination band that runs NNW from the FDNPS and it is nearly parallel with the major and heaviest contamination band in the west-northwest. The plume trace with a low 134Cs/137Cs ratio previously found by other researchers within the 3-km radius of the FDNPS is in a part of the area with the lower 134Cs/137Cs ratio anomaly that we found. Our result suggests that this lower 134Cs/137Cs ratio anomaly is the area which was contaminated before March 13, 2011 (UTC) in association with the hydrogen explosion of Unit 1 on March 12, 2011 at 06:36 (UTC) and it was less influenced by later subsequent plumes.

Thalamocortical Projections onto Behaviorally Relevant Neurons Exhibit Plasticity during Adult Motor Learning.

Layer 5 neurons of the neocortex receive direct and relatively strong input from the thalamus. However, the intralaminar distribution of these inputs and their capacity for plasticity in adult animals are largely unknown. In slices of the primary motor cortex (M1), we simultaneously recorded from pairs of corticospinal neurons associated with control of distinct motor outputs: distal forelimb versus proximal forelimb. Activation of ChR2-expressing thalamocortical afferents in M1 before motor learning produced equivalent responses in monosynaptic excitation of neurons controlling the distal and proximal forelimb, suggesting balanced thalamic input at baseline. Following skilled grasp training, however, thalamocortical input shifted to bias activation of corticospinal neurons associated with control of the distal forelimb. This increase was associated with a cell-specific increase in mEPSC amplitude but not presynaptic release probability. These findings demonstrate distinct and highly segregated plasticity of thalamocortical projections during adult learning.

Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration.

The corticospinal tract (CST) is the most important motor system in humans, yet robust regeneration of this projection after spinal cord injury (SCI) has not been accomplished. In murine models of SCI, we report robust corticospinal axon regeneration, functional synapse formation and improved skilled forelimb function after grafting multipotent neural progenitor cells into sites of SCI. Corticospinal regeneration requires grafts to be driven toward caudalized (spinal cord), rather than rostralized, fates. Fully mature caudalized neural grafts also support corticospinal regeneration. Moreover, corticospinal axons can emerge from neural grafts and regenerate beyond the lesion, a process that is potentially related to the attenuation of the glial scar. Rat corticospinal axons also regenerate into human donor grafts of caudal spinal cord identity. Collectively, these findings indicate that spinal cord 'replacement' with homologous neural stem cells enables robust regeneration of the corticospinal projection within and beyond spinal cord lesion sites, achieving a major unmet goal of SCI research and offering new possibilities for clinical translation.

Radioactive contamination mapping of northeastern and eastern Japan by a car-borne survey system, Radi-Probe.

We constructed a new car-borne survey system called Radi-Probe with a portable germanium gamma-ray spectrometer onboard a cargo truck, to identify radionuclides and quantify surface contamination from the accident at Fukushima Dai-ichi Nuclear Power Station. The system can quickly survey a large area and obtain ambient dose equivalent rates and gamma-ray energy spectra with good energy resolution. We also developed a new calibration method for the system to deal with an actual nuclear disaster, and quantitative surface deposition densities of radionuclides, such as (134)Cs and (137)Cs, and kerma rates of each radionuclide can be calculated. We carried out car-borne survey over northeastern and eastern Japan (Tohoku and Kanto regions of Honshu) from 25 September through 7 October 2012. We discuss results of the distribution of ambient dose equivalent rate H(∗)(10), (134)Cs and (137)Cs surface deposition densities, spatial variation of (134)Cs/(137)Cs ratio, and the relationship between surface deposition densities of (134)Cs/(137)Cs and H(∗)(10). The ratio of (134)Cs/(137)Cs was nearly constant within our measurement precision, with average 1.06 ± 0.04 in northeastern and eastern Japan (decay-corrected to 11 March, 2011), although small variations from the average were observed.