Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1–4 s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10 s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum to spatial working memory.DOI:
http://dx.doi.org/10.7554/eLife.19507.001
Accumulation of beta-amyloid (Aβ) in the brain has been implicated as a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer's disease. Beta-amyloid may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain. This study set out to investigate whether a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase (CAT-SKL), is able to reduce the toxicity induced by intracerebroventricular injection of Aβ in the mature rat brain. Histopathological and immunohistochemical analyses were used to evaluate neuroinflammation, and neuronal loss. Spatial learning and reference memory was assessed using the Morris water maze. CAT-SKL treatment was able to reduce the pathology induced by Aβ toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aβ animals showed deficits in long-term reference memory in the Morris water maze, while Aβ animals treated with CAT-SKL did not demonstrate long-term memory impairments. This preclinical data provides support for the use of CAT-SKL in reducing neuroinflammation and long-term reference memory deficits induced by Aβ
We systematically compared the contribution of two dopaminergic and two cholinergic ascending populations to a spatial short-term memory task in rats. In ventral tegmental area dopamine (VTA-DA) and nucleus basalis cholinergic (NB-ChAT) populations, trial-by-trial fluctuations in activity during the delay period related to performance with an inverted-U, despite the fact that both populations had low activity during that time. Transient manipulations revealed that only VTA-DA neurons, and not the other three populations we examined, contributed causally and selectively to short-term memory. This contribution was most significant during the delay period, when both increases or decreases in VTA-DA activity impaired short-term memory. Our results reveal a surprising dissociation between when VTA-DA neurons are most active and when they have the biggest causal contribution to short-term memory, while also providing new types of support for classic ideas about an inverted-U relationship between neuromodulation and cognition.
Total joint replacements can be subject to the loss of polyethylene material due to wear, leading to osteolysis and decreased implant longevity. Micro-computed tomography (micro-CT) techniques have recently been developed to calculate 3D surface deviations in worn implant components. We describe a micro-CT technique to measure the volume of the surface deviations (volume of wear plus creep) within a specific region or compartment, and report its repeatability and reproducibility. Six worn polyethylene tibial inserts were scanned using a laboratory micro-CT scanner and subsequently reconstructed at 50 μm voxel spacing. A previously developed custom software application was used to quantify the 3D surface deviations between the worn tibial inserts and an unworn reference geometry. Three observers (two trained and one expert) used new custom software to manually outline the localized regions of surface deviation (three times for each of the worn inserts) and calculate the volume of the deviations. The overall intraobserver variability in the surface deviation volumes was 3.6% medially and 1.1% laterally. The overall interobserver variability was 4.8% medially and 1.7% laterally. Placement of points in outlining the region of deviation contributed the greatest variability to the measurements. Repeatability and reproducibility of the volume measurements are similar to measurements of total (nonregional) wear volume including a previous micro-CT technique (10%), fluid displacement (4.8%), and radiographic measurements (15.7%). The principles of this technique can likely be used to measure regional wear and creep volume in knee and hip joint replacement components from wear simulator, pin-on-disk, and retrieval studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.