Inactivation of Medial Prefrontal Cortex Impairs Time Interval Discrimination in Rats

Several lines of evidence suggest the involvement of prefrontal cortex in time interval estimation. The underlying neural processes are poorly understood, however, in part because of the paucity of physiological studies. The goal of this study was to establish an interval timing task for physiological recordings in rats, and test the requirement of intact medial prefrontal cortex (mPFC) for performing the task. We established a temporal bisection procedure using six different time intervals ranging from 3018 to 4784 ms that needed to be discriminated as either long or short. Bilateral infusions of muscimol (GABAA receptor agonist) into the mPFC significantly impaired animal's performance in this task, even when the animals were required to discriminate between only the longest and shortest time intervals. These results show the requirement of intact mPFC in rats for time interval discrimination in the range of a few seconds

Functional Relationships between the Hippocampus and Dorsomedial Striatum in Learning a Visual Scene-Based Memory Task in Rats

The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies

Epigallocatechin-3-gallate protects toluene diisocyanate-induced airway inflammation in a murine model of asthma

AbstractEpigallocatechin-3-gallate (EGCG), a major form of tea catechin, has anti-allergic properties. To elucidate the anti-allergic mechanisms of EGCG, we investigated its regulation of matrix metalloproteinase (MMP-9) expression in toluene diisocyanate (TDI)-inhalation lung tissues as well as TNF-α and Th2 cytokine (IL-5) production in BAL fluid. Compared with untreated asthmatic mice those administrated with EGCG had significantly reduced asthmatic reaction. Also, increased reactive oxygen species (ROS) generation by TDI inhalation was diminished by administration of EGCG in BAL fluid. These results suggest that EGCG regulates inflammatory cell migration possibly by suppressing MMP-9 production and ROS generation, and indicate that EGCG may be useful as an adjuvant therapy for bronchial asthma

Effects of Methamphetamine on Single Unit Activity in Rat Medial Prefrontal Cortex In Vivo

To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA) administration. Systemic MA injection (4 mg/kg, IP) induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min) elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms

Complexity of Atherosclerotic Coronary Artery Disease and Long-Term Outcomes in Patients With Unprotected Left Main Disease Treated With Drug-Eluting Stents or Coronary Artery Bypass Grafting

ObjectivesThe aim of this study was to compare treatment effects of drug-eluting stents (DES) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease according to the complexity of atherosclerotic disease burden.BackgroundLimited information is available on the relationships between the extent of coronary atherosclerosis and very long-term outcomes of surgical or percutaneous LMCA revascularization.MethodsA total of 1,146 patients with unprotected LMCA disease who received DES (n = 645) or underwent CABG (n = 501) were evaluated. The extent of atherosclerotic disease burden was measured using the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score; a low-risk score was defined as ≤22, an intermediate-risk score as 23 to 32, and a high-risk score as ≥33.ResultsAfter multivariate adjustment with the inverse-probability-of-treatment weighting method, the 5-year risks for death (6.1% for DES vs. 16.2% for CABG; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.21 to 1.28; p = 0.15) and the composite of death, Q-wave myocardial infarction, or stroke (6.4% vs. 16.2%; HR: 0.54; 95% CI: 0.22 to 1.34; p = 0.18) favored DES in patients with low-risk SYNTAX scores; in contrast, the 5-year risks for death (26.9% vs. 17.8%; HR: 1.46; 95% CI: 0.92 to 2.30; p = 0.11) and the composite outcome (27.6% vs. 19.5%; HR: 1.36; 95% CI: 0.87 to 2.12; p = 0.18) favored CABG in patients with high-risk SYNTAX scores (interaction p = 0.047 for death, interaction p = 0.08 for composite outcome). Patients undergoing CABG consistently had lower rates of target vessel revascularization.ConclusionsAccording to the complexity of concomitant coronary disease, there were differential treatment effects on long-term mortality in patients with unprotected LMCA disease who received DES or underwent CABG

PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β

PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD