Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex.

Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex

Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

In early Alzheimer's disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks

Synthesis of satellite (MODIS), aircraft (ICARTT), and surface (IMPROVE, EPA-AQS, AERONET) aerosol observations over eastern North America to improve MODIS aerosol retrievals and constrain surface aerosol concentrations and sources

We use an ensemble of satellite (MODIS), aircraft, and ground-based aerosol observations during the ICARTT field campaign over eastern North America in summer 2004 to (1) examine the consistency between different aerosol measurements, (2) evaluate a new retrieval of aerosol optical depths (AODs) and inferred surface aerosol concentrations (PM2.5) from the MODIS satellite instrument, and (3) apply this collective information to improve our understanding of aerosol sources. The GEOS-Chem global chemical transport model (CTM) provides a transfer platform between the different data sets, allowing us to evaluate the consistency between different aerosol parameters observed at different times and locations. We use an improved MODIS AOD retrieval based on locally derived visible surface reflectances and aerosol properties calculated from GEOS-Chem. Use of GEOS-Chem aerosol optical properties in the MODIS retrieval not only results in an improved AOD product but also allows quantitative evaluation of model aerosol mass from the comparison of simulated and observed AODs. The aircraft measurements show narrower aerosol size distributions than those usually assumed in models, and this has important implications for AOD retrievals. Our MODIS AOD retrieval compares well to the ground-based AERONET data (R = 0.84, slope = 1.02), significantly improving on the MODIS c005 operational product. Inference of surface PM2.5 from our MODIS AOD retrieval shows good correlation to the EPA-AQS data (R = 0.78) but a high regression slope (slope = 1.48). The high slope is seen in all AOD-inferred PM2.5 concentrations (AERONET: slope = 2.04; MODIS c005: slope = 1.51) and could reflect a clear-sky bias in the AOD observations. The ensemble of MODIS, aircraft, and surface data are consistent in pointing to a model overestimate of sulfate in the mid-Atlantic and an underestimate of organic and dust aerosol in the southeastern United States. The sulfate overestimate could reflect an excessive contribution from aqueous-phase production in clouds, while the organic carbon underestimate could possibly be resolved by a new secondary pathway involving dicarbonyls

Experience-dependent firing rate remapping generates directional selectivity in hippocampal place cells

When rodents engage in irregular foraging in an open-field environment, hippocampal principal cells exhibit place-specific firing that is statistically independent of the direction of traverse through the place field. When the path is restricted to a track, however, in-field rates differ substantially in opposite directions. Frequently, the representations of the track in the two directions are essentially orthogonal. We show that this directionally selective firing is not hard-wired, but develops through experience-dependent plasticity. During the rats' first pass in each direction, place fields were highly directionally symmetric, whereas over subsequent laps, the firing rates in the two directions gradually but substantially diverged. We conclude that, even on a restricted track, place cell firing is initially determined by allocentric position, and only later, the within-field firing rates change in response to differential sensory information or behavioral cues in the two directions. In agreement with previous data, place fields near local cues, such as textures on the track, developed less directionality than place fields on a uniform part of the track, possibly because the local cues reduced the net difference in sensory input at a given point. Directionality also developed in an open environment without physical restriction of the animal's path, when rats learned to run along a specified path. In this case, directionality developed later than on the running track, only after the rats began to run in a stereotyped manner. Although the average population firing rates exhibited little if any change over laps in either direction, the direction-specific firing rates in a given place field were up-or down-regulated with about equal probability and magnitude, which was independent in the two directions, suggesting some form of competitive mechanism (e.g., LTP/LTD) acting coherently on the set of synapses conveying external information to each cell

Rathat: A self-targeting printable brain implant system

There has not been a major change in how neuroscientists approach stereotaxic methods in decades. Here, we present a new stereotaxic method that provides an alternative approach to a traditional u-frame stereotaxic device and reduces costs, surgical time, and aids repeatability. The RatHat brain implantation system is a 3Dprintable stereotaxic device for rats that is fabricated prior to surgery and fits to the shape of the skull. RatHat builds are directly implanted into the brain without the need for head-leveling or coordinate-mapping during surgery. The RatHat can be used in conjunction with the traditional u-frame stereotaxic device, but does not require the use of a micromanipulator for successful implantations. Each RatHat contains several primary components including the implant for mounting intracranial components, the surgical stencil for targeting drill sites, and the protective cap for preventing damage from impacts and debris. Each component serves a unique function and can be used together or separately. We demonstrate the feasibility of the RatHat in four different proof-of-principle experiments: (1) a three-pole cannula apparatus, (2) an optrode-electrode assembly, (3) a fixed-electrode array, and (4) a tetrode hyperdrive. Implants were successful, durable, and long-lasting (up to nine months). RatHat print files are easily created, can be modified in computer aided design (CAD) software for a variety of applications, and are easily shared, contributing to open science goals and replications. The RatHat has been adapted to multiple experimental paradigms in our lab and should be a useful new way to conduct stereotaxic implant surgeries in rodents

Emergency department utilization, admissions, and revisits in the United States (New York), Canada (Ontario), and New Zealand: A retrospective cross-sectional analysis.

BACKGROUND: Emergency department (ED) utilization is a significant concern in many countries, but few population-based studies have compared ED use. Our objective was to compare ED utilization in New York (United States), Ontario (Canada), and New Zealand (NZ). METHODS: A retrospective cross-sectional analysis of all ED visits between January 1, 2016, and September 30, 2017, for adults ≥18 years using data from the State Emergency Department and Inpatient Databases (New York), the National Ambulatory Care Reporting System and Discharge Abstract Data (Ontario), and the National Non-Admitted Patient Collection and the National Minimum Data Set (New Zealand). Outcomes included age- and sex-standardized per-capita ED utilization (overall and stratified by neighborhood income), ED disposition, and ED revisit and hospitalization within 30 days of ED discharge. RESULTS: There were 10,998,371 ED visits in New York, 8,754,751 in Ontario, and 1,547,801 in New Zealand. Patients were older in Ontario (mean age 51.1 years) compared to New Zealand (50.3) and New York (48.7). Annual sex- and age-standardized per-capita ED utilization was higher in Ontario than New York or New Zealand (443.2 vs. 404.0 or 248.4 visits per 1000 population/year, respectively). In all countries, ED utilization was highest for residents of the lowest income quintile neighborhoods. The proportion of ED visits resulting in hospitalization was higher in New Zealand (34.5%) compared to New York (20.8%) and Ontario (12.8%). Thirty-day ED revisits were higher in Ontario (27.0%) than New Zealand (18.6%) or New York (21.4%). CONCLUSIONS: Patterns of ED utilization differed widely across three high-income countries. These differences highlight the varying approaches that our countries take with respect to urgent visits, suggest opportunities for shared learning through international comparisons, and raise important questions about optimal approaches for all countries

Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy

Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy

Long-term recordings improve the detection of weak excitatory-excitatory connections in rat prefrontal cortex

Sherpa Romeo yellow journal. Open access article. Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported License (CC BY-NC-SA 3.0) applies.Characterization of synaptic connectivity is essential to understanding neural circuit dynamics. For extracellularly recorded spike trains, indirect evidence for connectivity can be inferred from short-latency peaks in the correlogram between two neurons. Despite their predominance in cortex, however, significant interactions between excitatory neurons (E) have been hard to detect because of their intrinsic weakness. By taking advantage of long duration recordings, up to 25 h, from rat prefrontal cortex, we found that 7.6% of the recorded pyramidal neurons are connected. This corresponds to 70% of the local E–E connection probability that has been reported by paired intracellular recordings(11.6%). This value is significantly higher than previous reports from extracellular recordings, but still a substantial underestimate. Our analysis showed that long recording times and strict significance thresholds are necessary to detect weak connections while avoiding false-positive results, but will likely still leave many excitatory connections undetected. In addition, we found that hyper-reciprocity of connections in prefrontal cortex that was shown previously by paired intracellular recordings was only present in short-distance, but not in long distance (300 micrometers or more) interactions. As hyper-reciprocity is restricted to local clusters, it might be a mini columnar effect. Given the current surge of interest in very high-density neural spike recording (e.g., NIH BRAIN Project) it is of paramount importance that we have statistically reliable methods for estimating connectivity from cross-correlation analysis available. We provide an important step in this direction.Ye