Electric activity in the neocortex of freely moving young and aged rats

Electroencephalographic activity of the neocortex was evaluated in young (5-7 months) and aged (26-28 months) rats. All animals in the aged group showed behavioral impairment in a spatial task (water maze). A neocortical electroencephalogram was derived simultaneously from 16 different neocortical locations and was subjected to spectral analysis. The frequency of occurrence and duration of high-voltage spindles was determined in two sessions, each involving a total of 30 min alert immobility. Changes in spectral characteristics and high-voltage spindles in response to scopolamine administration were also evaluated. The power of high-frequency activity (8-20 Hz) was significantly reduced in the aged subjects. This was greatest in the temporo-occipital regions, while no significant changes were seen in the mediofrontal region. Scopolamine resulted in a large power increase in all frequency bands, but the increase in the higher-frequency range (8-20 Hz) was significantly less in the aged group. The incidence of high-voltage spindles was 6 times higher and their total duration was 9 times longer in aged rats, with virtually no overlap with the young group. In young rats, scopolamine increased the incidence and total duration of high-voltage spindles, while it decreased both parameters in the aged subjects. Cholinergic neurons in the nucleus basalis appeared shrunken in the aged animals. These findings demonstrate that reliable electroencephalographic changes are present in the neocortex of the aged rat, and that some of the physiological alterations may be due to the pathological changes in the cholinergic nucleus basalis.     

Spatial learning and memory following fimbria-fornix transection and grafting of fetal septal neurons to the hippocampus

Summary The ability of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in developing cholinergic neurons, to ameliorate cognitive impairments induced by bilateral fimbria-fornix transections in rats was examined in three experiments using the Morris water-maze to test different aspects of spatial memory. Experiment 1. Rats with fimbria-fornix lesions received either septal cell suspension grafts or solid septal grafts; normal rats and rats with lesions alone were used as controls. Sixteen weeks after surgery, the rats' spatial learning and memory were tested in the water-maze using a place test, designed to investigate place navigation performance, in which rats learned to escape from the water by swimming to a platform hidden beneath the water's surface. After 5 days of training, the rats were given a spatial probe test in which the platform was removed from the tank to test spatial reference memory. Experiment 2. The same rats used in Exp. 1 were tested in a delayed-match-to-sample, working memory version of the water-maze task. The platform was located in one of two possible locations during each trial, which was composed of 2 swims. If the rat remembered the location of the platform on the 2nd swim of a trial, it should find the platform more quickly on that swim, and thereby demonstrate working memory. Experiment 3. Prior to receiving fimbria-fornix lesions, normal rats were trained in a modification of the water-maze task using alternating cue navigation and place navigation trials (i.e., with visible or non-visible escape platforms). The retention and reacquisition of the place task and the spatial probe test were examined in repeated tests up to 6 months after the lesion and intrahippocampal grafting of septal cell suspensions. The effects of central muscarinic cholinergic receptor blockade with atropine were also tested. Normal rats performed well in both the place and spatial probe tests. In contrast, rats with fimbria-fornix lesions only were unable to acquire or retain spatial information in any test. Instead, these rats adopted a random, nonspatial search strategy, whereby their latencies to find the platform decreased in the place navigation tasks. Sixty to 80% of the rats with septal suspension or solid grafts had recovered place navigation, i.e., the ability to locate the platform site in the tank, in Exp. 1 and 3, and they showed a significantly improved performance in the working memory test in Exp. 2. Atropine abolished the recovered place navigation in the grafted rats, whereas normal rats were impaired to a lesser extent. In contrast, atropine had no effect on the non-spatial strategy adopted by rats with fimbria-fornix lesions only. The results show that: (1) fimbria-fornix lesions disrupt spatial learning and memory in both naive and pretrained rats; (2) with extended training the fimbria-fornix lesioned rats develop an efficient non-spatial strategy, which enables them to reduce their escape latency to levels close to those of intact controls; (3) intrahippocampal septal grafts can restore the ability of the lesioned rats to use spatial cues in the localization of the platform site; and (4) the behavioural recovery produced by grafts is dependent upon an atropine sensitive mechanism.     

Managing the cancer risk in chronic ulcerative colitis. A decision-analytic approach

Chronic ulcerative colitis is associated with a high risk of colon cancer. The most appropriate management--prophylactic proctocolectomy or medical surveillance--is, at present, unclear. Recent reports suggest that the presence of colonic dysplasia or "precancer" on endoscopic biopsy may be a reliable predictor of concurrent or future colon cancer. To assess the value of colonic dysplasia in managing colitis patients, I applied decision analytic techniques to currently available data regarding the sensitivity and specificity of colonic dysplasia in colitis patients. Such analysis shows that management based on biopsy for colonic dysplasia, rather than prophylactic proctocolectomy for all colitis patients, will maximize 5-year survival. Sensitivity analysis suggests that management is primarily determined by the sensitivity of biopsy-diagnosed dysplasia--elective prophylactic surgery would be preferred only when sensitivity of dysplasia on biopsy is less than or equal to 0.70 at 20 years, or less than or equal to 0.85 at 30 years of colitis, and changing surgical mortality and survival benefit from early diagnosis within a range established by previous studies affects management decisions only when sensitivity of dysplasia is at the lower end of its reported range.     

The Frequency and Context of Snacking among Children: An Objective Analysis Using Wearable Cameras

Snacking is a common eating behaviour, but there is little objective data about children’s snacking. We aimed to determine the frequency and context of children’s snacking (n = 158; mean age = 12.6 years) by ethnicity, gender, socioeconomic deprivation and body mass index (BMI) children. Participants wore wearable cameras that passively captured images of their surroundings every seven seconds. Images (n = 739,162) were coded for snacking episodes, defined as eating occasions in between main meals. Contextual factors analysed included: snacking location, food source, timing, social contact and screen use. Rates of total, discretionary (not recommended for consumption) and healthful (recommended for consumption) snacking were calculated using negative binomial regression. On average, children consumed 8.2 (95%CI 7.4, 9.1) snacks per day, of which 5.2 (95%CI 4.6, 5.9) were discretionary foods/beverages. Children consumed more discretionary snacks than healthful snacks in each setting and at all times, including 15.0× more discretionary snacks in public spaces and 2.4× more discretionary snacks in schools. Most snacks (68.9%) were sourced from home. Girls consumed more total, discretionary and healthful snacks than boys, and Māori and Pacific consumed fewer healthful snacks than New Zealand (NZ) Europeans. Results show that children snack frequently, and that most snacking involves discretionary food items. Our findings suggest targeting home buying behaviour and environmental changes to support healthy snacking choices.     

Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo

We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. Weak theta-patterned stimulation, which did not produce LTP in control subjects, produced a robust and long-lasting LTP in Runners. LTP induction in both groups was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl] propanephosphonic acid. Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.     

Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles

The subgranule zone of the dentate gyrus in rats has been shown to be proliferative into adulthood and senescence. However, the connectivity of newly generated, identified neurons in the adult has not been definitively described. In the present study, 9 weeks after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU), animals received stereotaxic iontophoretic injections of Fluoro-Gold (FG) into field CA3. Three weeks after FG injections, sections were analyzed for BrdU immunoreactivity (proliferative label), FG retrograde label, and either calbindin-D28k or synaptophysin immunohistochemistry. A large proportion (up to 44%) of BrdU-labeled cells in the dentate gyrus within regions of FG retrograde label incorporated FG. All of the doubly labeled (BrdU-FG) neurons also immunolabeled with the antibody to calbindin-D28k. Many doubly labeled (BrdU-FG) cells were also surrounded in three planes by synaptophysin immunoreactivity. We conclude that newly generated neurons in the dentate gyrus have the correct immunohistochemical profile, send appropriate axonal projections to field CA3, and are surrounded by profiles containing synaptic vesicle proteins.     

State-level variation in Medicare spending

Theoretically, Medicare provides one standard benefit package to all enrollees. But because of State-level variations in populations, service supply, and local practice patterns, national policy changes may have unequal impacts on access and service utilization. Across-the-board policy changes may create hardships in one area while appropriately discouraging use in another area. In this article, the authors describe State-level variations in Medicare enrollees, their insurance coverage, 1995 Medicare and beneficiary spending patterns in aggregate, per capita, and by service, and certain spending patterns for dually eligible beneficiaries. These data are useful for considering the State-level effects of payment reform.     

Physiological and behavioral consequences of delayed septal grafts in the subcortically denervated hippocampus

The present experiments examined whether cholinergic grafts reverse the physiological and behavioral deficits of the damaged hippocampus. Fimbria-fornix lesions were performed in young rats and 3 months later half of the lesioned rats received cholinergic-rich basal forebrain transplants. Eight months after grafting we tested the animals behaviorally in the water maze. Following the behavioral experiments, the animals were implanted with chronic recording and stimulating electrodes and the electrical properties of the hippocampus, including spontaneous EEG, interictal spikes, evoked responses, long-term potentiation, and sensitivity to induced seizures were examined. Grafted rats did not show statistically reliable behavioral recovery (swim latencies, swim path lengths) and their performance was identical to the lesion-only group. Acetylcholinesterase reinnervation of the host hippocampus in grafted animals was similar to intact rats; the grafts also contained numerous parvalbumin-immunoreactive neurons. The most striking physiological change was the significant elevation of seizure threshold in the grafted group, but other physiological parameters did not improve consistently. The findings suggest that the presence of septal tissue grafts and restoration of cholinergic reinnervation in animals with previous subcortical denervation of the hippocampus are not sufficient to restore normal hippocampal electrical patterns or to improve behavioral performance.     

Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature and mature dystrophic rats

Attempts to repopulate the retina with grafted neurons have been unsuccessful, in large part because donor cells prefer not to integrate with those of the host. Here we describe the first use of neural progenitor cells in the diseased adult retina. Adult rat hippocampal progenitor cells were injected into the eyes of rats with a genetic retinal degeneration. After survival times up to 16 weeks, the retinae of 1-, 4-, and 10-week-old recipients exhibited widespread incorporation of green fluorescent protein-expressing (GFP+) donor cells into the host retina. The 18-week-old recipients showed a similar pattern, but with fewer cells. Grafted cells expressed the mature neuronal markers NF-200, MAP-5, and calbindin. GFP+ cells extended numerous neurites into the host plexiform layers and these processes were intimately associated with synaptophysin+ profiles. GFP+ neurites also extended into the host optic nerve head. These results demonstrate the differentiation of substantial numbers of new neurons within the mature dystrophic retina.