Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults.

In understanding the mechanism of schizophrenia pathogenesis, a significant finding is that drug abuse of phencyclidine or its analog ketamine causes symptoms similar to schizophrenia. Such drug effects are triggered even by administration at post-adolescent stages. Both drugs are N-methyl-d-aspartate receptor (NMDAR) antagonists, leading to a major hypothesis that glutamate hypofunction underlies schizophrenia pathogenesis. The precise region that depends on NMDAR function, however, is unclear. Here, we developed a mouse strain in which NMDARs in the intralaminar thalamic nuclei (ILN) were selectively disrupted. The mutant mice exhibited various schizophrenia-like phenotypes, including deficits in working memory, long-term spatial memory, and attention, as well as impulsivity, impaired prepulse inhibition, hyperlocomotion and hyperarousal. The electroencephalography analysis revealed that the mutant mice had a significantly reduced power in a wide range of frequencies including the alpha, beta and gamma bands, both during wake and rapid eye movement (REM) sleep, and a modest decrease of gamma power during non-REM sleep. Notably, restoring NMDARs in the adult ILN rescued some of the behavioral abnormalities. These findings suggest that NMDAR dysfunction in the ILN contributes to the pathophysiology of schizophrenia-related disorders. Furthermore, the reversal of inherent schizophrenia-like phenotypes in the adult mutant mice supports that ILN is a potential target site for a therapeutic strategy.

Top-down cortical input during NREM sleep consolidates perceptual memory.

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation.

Appendicitis in De Garengeot's Hernia Presenting as a Nontender Inguinal Mass: Case Report and Review of the Literature.

Introduction. De Garengeot first described a femoral hernia containing the appendix in 1731. Appendicitis occurring in this rare clinical setting represents a challenge in diagnosis and management. Case Presentation. We present the case of a 71-year-old male with a three-day history of a nontender inguinal mass. Computed tomography (CT) suggested a femoral hernia. Intraoperatively, the hernia sac was noted to contain a perforated appendix. Discussion. This is an infrequently reported clinical scenario and only the 14th reported case in peer-reviewed literature which includes preoperative CT images. Our case adds to previously reported low sensitivity of CT for diagnosing De Garengeot's hernia. Furthermore, unlike our case the vast majority of previous reports noted a painful inguinal swelling. Conclusion. Perforated appendicitis in a femoral hernia is an extremely uncommon presentation. However, consideration should be given to De Garengeot's hernia in patients with a groin mass, even if nontender.

Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice.

To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of pairs of neurons tuned to similar spatial locations. Pairs have uncorrelated firing even if their fields overlap. These results demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the proper representation of space in the CA1 region of the hippocampus.

Observation of the reduction and reoxidation of the primary electron acceptor in photosystem I.

Femtosecond transient absorption spectroscopy has been used to investigate the primary charge separation in a photosystem II deletion mutant from the cyanobacterium Synechocystis sp. PCC 6803. These cells contain only the photosystem I reaction center and have a pigment content of approximately 100 chlorophylls per P700. Utilizing relatively high excitation intensities, the difference spectrum for the reduction of primary electron acceptor [(A0(-)-A0) difference spectrum] was obtained from experiments performed under both reducing and oxidizing conditions. Both approaches yield very similar results with the (A0(-)-A0) difference spectrum displaying a maximum bleaching at 687 nm. The shape of the difference spectrum suggests that the primary electron acceptor in photosystem I may be a chlorophyll a molecule. The observed rate of primary radical pair formation depends on the overall rate of decay of excitations in the antenna; the radical pair state forms as the antenna decays. The decay of the primary radical pair state is characterized by a 21-ps time constant. Under conditions that avoid annihilation effects, the mean lifetime for excitations in the antenna is 28 ps [Hastings, G., Kleinherenbrink, F.A.M., Lin, S., & Blankenship, R.E. (1994) Biochemistry (preceding paper in this issue)]. This indicates that the reduced acceptor decays faster than it forms. Therefore, only a low concentration of the reduced acceptor will accumulate under most conditions.