Recognition Memory Induces Natural LTP-like Hippocampal Synaptic Excitation and Inhibition

Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3–CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABA_A-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3–CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.     

Prolonged administration of oral etoposide alone or with intravenous carboplatin in stage IV non-small cell lung cancer: a randomized trial

Alzheimer's disease (AD) is characterized by neuronal cell death and two kinds of deposits, neurofibrillary tangles (NFT) and senile plaques. The main component of NFT is paired helical filaments (PHF), which mainly consist of hyperphosphorylated tau protein. Tau protein kinases I and II were found as candidate enzymes responsible for hyperphosphorylation of tau to induce the formation of PHF. Since prior phosphorylation of tau by TPKII strongly enhanced the action of TPKI, it was thought that TPKII was involved in the formation of PHF-tau in concert with TPKI. After cloning, TPKI was found to be identical with glycogen synthase kinase 3 beta (GSK3 beta), while TPKII consists of a novel 23 kDa protein activator and a catalytic subunit that is identical with cyclin-dependent kinase 5 (CDK5). The phosphorylation sites on tau by TPKI and TPKII could account for the most, but not all, of the major phosphorylation sites of fetal tau and PHF-tau. An antibody for a site specifically phosphorylated by TPKI (Ser413) could identify all three neurofibrillary lesions in the AD brain, and double staining for either TPKI or TPKII and NFT in the brain of Down's syndrome patients clearly demonstrated that TPKI and TPKII are both associated with NFT in vivo, suggesting that the level of TPKI or TPKII is elevated in AD brain by some mechanism. On the other hand, the levels of both TPKs change developmentally, being high in the neonatal period when the phosphorylation of fetal tau proceeds actively, suggesting that the TPKI/TPKII cooperative system has an important physiological role in the formation of neural networks. In AD brain, aberrant accumulation of amyloid-beta protein (A beta) occurs ahead of the accumulation of PHF in NFT. When a primary culture of embryonic rat hippocampus was treated with 20 microM A beta, induction of TPKI, extensive phosphorylation of tau and then programmed cell death were observed, indicating that TPKI induced by A beta phosphorylates tau, followed by disruption of axonal transportation and finally cell death. By using a yeast two hybrid system, TPKI was found to interact with pyruvate dehydrogenase (PDH), which is a key enzyme in the glycolytic pathway. PDH was phosphorylated in vitro by TPKI to reduce the activity converting pyruvate into acetyl-CoA, which is required for acetylcholine synthesis. In a primary culture of rat hippocampal cells treated with A beta, PDH was inactivated in inverse relation to the activation of TPKI, resulting in accumulation of pyruvate or lactate, energy failure induced by the disturbance of glucose metabolism, and a shortage of acetylcholine owing to deficiency of acetyl-CoA, all of which are characteristic of AD brain. In cholinergic neurons such as those of the septum, non-aggregated A beta, specifically A beta (1-42), not A beta (1-40), caused a shortage of acetylcholine by activation of TPKI and inactivation of PDH without cell death.     

The influence of heat treatment on the sliding wear behavior of a ZA-27 alloy

The effects of heat treatment, involving solutionizing at temperature of 370 °C for a relatively short period of time (3 or 5 h), followed by quenching in water, on tribological behavior of ZA-27 alloys were examined.Dry sliding wear tests were conducted on as-cast and heat-treated ZA-27 samples using block-on-disk machine over a wide range of applied loads. To determine the wear mechanisms, the worn surfaces of the samples were examined by scanning electron microscopy (SEM). The tribological results were related to the microstructure and mechanical properties.The heat treatment resulted in reduction in the hardness and tensile strength but increase in elongation. The heat-treated alloy samples attained improved tribological behavior over the as-cast ones, both from the aspects of friction and wear. The improved tribological behavior of the heat-treated alloys, in spite of reduced hardness, could be the result of breaking the dendrite structure, when the fraction of interdendrite regions was considerably decreased and a very fine α and η mixture was formed at the same time. The wear response of the samples has been corroborated through characteristics of worn surfaces and dominant wear mechanisms.     

OFDM channel estimation in the presence of interference

We develop a frequency-domain channel estimation algorithm for single-user multiantenna orthogonal frequency division multiplexing (OFDM) wireless systems in the presence of synchronous interference. In this case, the synchronous interferer's signal on each OFDM subcarrier is correlated in space with a rank one spatial covariance matrix. In addition, the interferer's spatial covariance matrix is correlated in frequency based on the delay spread of the interferer's channel. To reduce the number of unknown parameters we develop a structured covariance model that accounts for the structure resulting from the synchronous interference. To further reduce the number of unknown parameters, we model the covariance matrix using a priori known set of frequency-dependent functions of joint (global) parameters. We estimate the interference covariance parameters using a residual method of moments (RMM) estimator and the channel parameters by maximum likelihood (ML) estimation. Since our RMM estimates are invariant to the mean, this approach yields simple noniterative estimates of the covariance parameters while having optimal statistical efficiency. Hence, our algorithm outperforms existing channel estimators that do not account for the interference, and at the same time requires smaller number of pilots than the MANOVA method and thus has smaller overhead. Numerical results illustrate the applicability of the proposed algorithm.