An infrastructure for qualified data sharing and team science in late-stage translational spinal cord injury research.

The complex and heterogeneous nature of spinal cord injury has limited translational bench-to-bedside results. The wide variety of data, including injury parameters, biochemical, histological, and behavioral outcome measures represent a 'big data' problem, calling for modern data science solutions. There are some instances in which SCI researchers collect sensitive data that needs to remain private, such as datasets designed to meet regulatory approval, sensitive intellectual property, and non-human primate studies. For these types of data, we have developed a Private Data Commons for SCI (PDC-SCI). Our objective is to give an overview of this novel data commons, describing how this type of commons works, how it can benefit the research community, and the cases in which it would be most useful. This private infrastructure is ideal for multi-lab transdisciplinary studies that require a well-organized, scalable data commons for rapid data sharing within a closed, distributed team. As a use-case for the PDC-SCI, we demonstrate the VA Gordon Mansfield SCI Consortium, in which multimodal data from behavior, biomechanics of injury, hospital records, imaging, and histology are integrated, shared, and analyzed to facilitate insights and knowledge discovery.

Enhanced axonal transport: A novel form of "plasticity" after primate and rodent spinal cord injury.

Deficient axonal transport after injury is believed to contribute to the failure of CNS regeneration. To better elucidate neural mechanisms associated with CNS responses to injury, we transected the dominant voluntary motor system, the corticospinal tract (CST), in the dorsolateral T10 spinal cord of rhesus monkeys. Three months later, a 4.5-fold increase in the number of CST axons located in the spared ventral corticospinal tract at both the lesion site and, surprisingly, remotely in the cervical spinal cord was observed. Additional studies of increases in corticospinal axon numbers in rat and primate models demonstrated that increases were transient and attributable to enhanced axonal transport rather than axonal sprouting. Accordingly, increases in axonal transport occur after CNS injury even in the longest projecting pathways of the non-human primate, likely representing an attempted adaptive response to injury as observed in the PNS.

Dynamics of hippocampal ensemble activity realignment: time versus space.

Whether hippocampal map realignment is coupled more strongly to position or time was studied in rats trained to shuttle on a linear track. The rats were required to run from a start box and to pause at a goal location at a fixed location relative to stable distal cues (room-aligned coordinate frame). The origin of each lap was varied by shifting the start box and track as a unit (box-aligned coordinate frame) along the direction of travel. As observed by Gothard et al. (1996a), on each lap the hippocampal activity realigned from a representation that was box-aligned to one that was room-aligned. We studied the dynamics of this transition using a measure of how well the moment-by-moment ensemble activity matched the expected activity given the location of the animal in each coordinate frame. The coherency ratio, defined as the ratio of the matches for the two coordinate systems, provides a quantitative measure of the ensemble activity alignment and was used to compare four possible descriptions of the realignment process. The elapsed time since leaving the box provided a better predictor of the occurrence of the transition than any of the three spatial parameters investigated, suggesting that the shift between coordinate systems is at least partially governed by a stochastic, time-dependent process.

Independence of firing correlates of anatomically proximate hippocampal pyramidal cells.

In neocortex, neighboring neurons frequently exhibit correlated encoding properties. There is conflicting evidence whether a similar phenomenon occurs in hippocampus. To assess this quantitatively, a comparison was made of the spatial and temporal firing correlations within and between local groups of hippocampal cells, spaced 350-1400 microm apart. No evidence of clustering was found in a sample of >3000 neurons. Moreover, cells active in two environments were uniformly interspersed at a scale of <100 microm, as assessed by the activity-induced gene Arc. Independence of encoding characteristics implies uncorrelated inputs, which could enhance the capacity of the hippocampus to store arbitrary associations.

Role of temporal summation in age-related long-term potentiation-induction deficits.

Hippocampal long-term potentiation (LTP) is reduced in aged relative to young F-344 rats when peri-threshold stimulation protocols (several stimulus pulses at 100-200 Hz) are used. The present study was designed to examine the possibility that this LTP-induction deficit is caused by a reduced overlap of Schaffer-collateral inputs onto CA1 pyramidal cells (input cooperativity). This reduced input cooperativity would decrease the levels of postsynaptic depolarization during LTP induction, which might account for the age-related LTP deficit. Both behavioral data (Morris Water Maze) and electrophysiological data (intracellular recordings from hippocampal slices) were collected from adult and aged F-344 rats. To counter the effects of reduced input cooperativity, stimulus intensities were adjusted to elicit baseline excitatory postsynaptic potentials (EPSPs) of equivalent amplitude in aged and young rats. Contrary to expectations, however, an age-related LTP-induction deficit was still observed. Further evaluation of the electrophysiological data revealed that temporal summation of multiple EPSPs during high-frequency stimulation was impaired in the aged rats. Thus, despite the equalization across age groups of the baseline EPSP amplitudes, the cells of aged rats were less depolarized during the LTP-inducing stimulation than were those of young rats. This reduced total depolarization was not an artifact of the higher stimulus intensity used on aged animals, nor was it caused by a failure of aged rats' CA1 afferents to follow high-frequency stimulation. The present data therefore suggest that there is a deficit in the ability of aged rats' synapses to provide the sustained depolarization necessary to active the LTP-induction cascade.