Medial entorhinal-hippocampal desynchronization parallels the emergence of memory impairment in a mouse model of Alzheimer's disease pathology.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive impairments in episodic and spatial memory, as well as circuit and network-level dysfunction. While functional impairments in medial entorhinal cortex (MEC) and hippocampus (HPC) have been observed in patients and rodent models of AD, it remains unclear how communication between these regions breaks down in disease, and what specific physiological changes are associated with the onset of memory impairment. We used silicon probes to simultaneously record neural activity in MEC and hippocampus before or after the onset of spatial memory impairment in the 3xTg mouse model of AD pathology.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy.

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous electrophysiology in hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits.

Progressive Excitability Changes in the Medial Entorhinal Cortex in the 3xTg Mouse Model of Alzheimer's Disease Pathology.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in hippocampus, but less is known about changes in medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at 3 and 10 months of age in the 3xTg mouse model of AD pathology, using male and female mice.

Chronotate: An open-source tool for manual timestamping and quantification of animal behavior.

A core necessity to behavioral neuroscience research is the ability to accurately measure performance on behavioral assays, such as the novel object location and novel object recognition tasks. These tasks are widely used in neuroscience research and measure a rodent's instinct for investigating novel features as a proxy to test their memory of a previous experience. Automated tools for scoring behavioral videos can be cost prohibitive and often have difficulty distinguishing between active investigation of an object and simply being in close proximity to an object.

Progressive excitability changes in the medial entorhinal cortex in the 3xTg mouse model of Alzheimer's disease pathology.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in the hippocampus, but less is known about what happens in the medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured the neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at early (3 months) and late (10 months) time points in the 3xTg mouse model of AD pathology.

Breakdown of spatial coding and interneuron synchronization in epileptic mice.

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation.

ezTrack: An open-source video analysis pipeline for the investigation of animal behavior.

Tracking animal behavior by video is one of the most common tasks in the life sciences. Although commercial software exists for executing this task, they often present enormous cost to the researcher and can entail purchasing hardware that is expensive and lacks adaptability. Additionally, the underlying code is often proprietary.

Decline of prefrontal cortical-mediated executive functions but attenuated delay discounting in aged Fischer 344 × brown Norway hybrid rats.

Despite the fact that prefrontal cortex (PFC) function declines with age, aged individuals generally show an enhanced ability to delay gratification, as evident by less discounting of delayed rewards in intertemporal choice tasks. The present study was designed to evaluate relationships between 2 aspects of PFC-dependent cognition (working memory and cognitive flexibility) and intertemporal choice in young (6 months) and aged (24 months) Fischer 344 × brown Norway F1 hybrid rats. Rats were also evaluated for motivation to earn rewards using a progressive ratio task.

Broadband observations of the naked-eye gamma-ray burst GRB 080319B.

Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks.

Gastric mucosal pH as a prognostic index of mortality in critically ill patients.

Objective: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality.

Design: Prospective comparison of outcome.

Setting: General adult ICUs in two teaching hospitals.

Postoperative acute gastrointestinal tract hemorrhage and multiple-organ failure.

Acute upper gastrointestinal tract hemorrhage (AUGH) was evaluated postoperatively in 720 critically ill patients and correlated with multiple-organ failure (MOF). The AUGH incidence was 20.1%.

Regulation of the mitochondrial anabolism at low concentrations of thyroid hormones and by some of their structural analogues.

The Authors demonstrate that the in vitro stimulation of mitochondrial RNA synthesis produced by thyroid hormones takes place also at physiological levels, equal to those held in the liver cells of experimental animals. Two groups of male rats have been used: normal control animals (N) and animals surgically thyroidectomized on the 25th day of life (T). The animals were fed and kept in standard conditions and killed on the 85th day of life.