It is shown that, particularly for terrestrial cellular telephony, the interference-suppression feature of CDMA (code division multiple access) can result in a many-fold increase in capacity over analog and even over competing digital techniques. A single-cell system, such as a hubbed satellite network, is addressed, and the basic expression for capacity is developed. The corresponding expressions for a multiple-cell system are derived. and the distribution on the number of users supportable per cell is determined. It is concluded that properly augmented and power-controlled multiple-cell CDMA promises a quantum increase in current cellular capacity. >

On the capacity of a cellular CDMA system

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

/pdf/schizophrenia-risk-from-complex-variation-of-complement-q3hqk5p1zk.pdf

Schizophrenia risk from complex variation of complement component 4

저작근 근전도에 관한 정상교합자와 ii급 부정교합자의 비교 연구

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.

Multimodal fast optical interrogation of neural circuitry

The excitability of somatic membrane of Helix lucorum neurons was studied by means of extracellular electric current of various direction (frequency 0.1 Hz). Inhomogenous excitability of somatic membrane was shown and the existence of the local low-threshold area of spike generation in the soma was demonstrated.

[Low-threshold area of action potential generation in the somatic membrane of mollusk neurons].

Decrease of effectivity of "competing" synaptic input requires protein synthesis.

Subcellular targeting of opsins in optogenetics provides new possibilities for investigating the function of nerve cells. One of the widely used motifs for central targeting of opsins is the motif of potential-dependent potassium channel Kv2.1. We have expressed construct CHR2-Venus-Kv2.1 in the layer 2/3 pyramidal neurons of the murine cerebral cortex by means of in utero electroporation. It was found that, although the majority of neurons expressing CHR2-Venus-Kv2.1 demonstrated mainly central localization of fluorescence in the soma, proximal dendrites and axon, there was also significant population of neurons with disruption of the “correct” targeting resulting in the fluorescent protein distributed uniformly throughout the entire cell surface. We have suggested that observed mislocalization was caused by overexpression of the construct. Indeed, a decrease in the plasmid concentration during the in utero electroporation procedure resulted in almost complete absence of neurons with altered targeting. Thus, the possibility of “incorrect” targeting of CHR2 by the potassium channel motif Kv2.1 should be taken into account when using this construct in optogenetic experiments.

/pdf/central-targeting-of-channelrodopsin2-by-motif-of-potassium-2xlm123ufy.pdf

Central Targeting of Channelrodopsin2 by Motif of Potassium Channel Kv2.1 Can Be Altered Due to Overexpression of Construct

Widening and deepening our understanding of how the brain works requires constant improvements not only in methods of recording neuron activity, but also improvements in experimental approaches to activating individual cells and their compartments. Optogenetic stimulation methods using finely focused light to trigger the opening of the light-activated depolarizing cation channel rhodopsin-2 (ChR2) have become widely used in recent years. Current molecular biological methods provide for the genetic expression of ChR2 in different cell types, which, along with the ability to carry out electrophysiological experiments with reproducible patterns of activation and stable levels of ChR2 expression, have developed optogenetics into an effective method for gathering physiological data previously unavailable to conventional methods. We report here the use of local activation of axons using an optogenetic stimulation method. Experiments were performed in combination with recording the electrical activity of neurons using the patch-clamp method, as well as laser scanning confocal microscopy. Experiments used the transgenic mouse strain Thy1-ChR2-YFP, in which ChR2 is expressed in only a small proportion of pyramidal cells. Direct studies of the effects of functional activity in the proximal branches of pyramidal neuron axons in layer 5 of the visual cortex and hippocampal field CA1 on the shape and generation of action potentials were carried out. We also describe methodological advances and means of solving problems encountered in the optogenetic stimulation of the axons of pyramidal neurons in the central nervous system of mammals.

Optogenetic Stimulation of the Axons of Visual Cortex and Hippocampus Pyramidal Neurons in Living Brain Slices

The search for strategies for strengthening the synaptic efficiency in Aβ25-35-treated slices is a challenge for the compensation of amyloidosis-related pathologies. Here, we used the recording of field excitatory postsynaptic potentials (fEPSPs), nitric oxide (NO) imaging, measurements of serine/threonine protein phosphatase (STPP) activity, and the detection of the functional mitochondrial parameters in suspension of brain mitochondria to study the Aβ25-35-associated signaling in the hippocampus. Aβ25-35 aggregates shifted the kinase–phosphatase balance during the long-term potentiation (LTP) induction in the enhancement of STPP activity. The PP1/PP2A inhibitor, okadaic acid, but not the PP2B blocker, cyclosporin A, prevented Aβ25-35-dependent LTP suppression for both simultaneous and delayed enzyme blockade protocols. STPP activity in the Aβ25-35-treated slices was upregulated, which is reverted relative to the control values in the presence of PP1/PP2A but not in the presence of the PP2B blocker. A selective inhibitor of stress-induced PP1α, sephin1, but not of the PP2A blocker, cantharidin, is crucial for Aβ25-35-mediated LTP suppression prevention. A mitochondrial Na+/Ca2+ exchanger (mNCX) blocker, CGP37157, also attenuated the Aβ25-35-induced LTP decline. Aβ25-35 aggregates did not change the mitochondrial transmembrane potential or reactive oxygen species (ROS) production but affected the ion transport and Ca2+-dependent swelling of organelles. The staining of hippocampal slices with NO-sensitive fluorescence dye, DAF-FM, showed stimulation of the NO production in the Aβ25-35-pretreated slices at the dendrite-containing regions of CA1 and CA3, in the dentate gyrus (DG), and in the CA1/DG somata. NO scavenger, PTIO, or nNOS blockade by selective inhibitor 3Br-7NI partly restored the Aβ25-35-induced LTP decline. Thus, hippocampal NO production could be another marker for the impairment of synaptic plasticity in amyloidosis-related states, and kinase–phosphatase balance management could be a promising strategy for the compensation of Aβ25-35-driven deteriorations.

/pdf/amyloid-ab25-35-aggregates-say-no-to-long-term-potentiation-3t7370hl.pdf

Amyloid Aβ25-35 Aggregates Say ‘NO’ to Long-Term Potentiation in the Hippocampus through Activation of Stress-Induced Phosphatase 1 and Mitochondrial Na+/Ca2+ Exchanger

Pavel M. Balaban

Papers

[Low-threshold area of action potential generation in the somatic membrane of mollusk neurons].

Decrease of effectivity of "competing" synaptic input requires protein synthesis.

Central Targeting of Channelrodopsin2 by Motif of Potassium Channel Kv2.1 Can Be Altered Due to Overexpression of Construct

Optogenetic Stimulation of the Axons of Visual Cortex and Hippocampus Pyramidal Neurons in Living Brain Slices

Amyloid Aβ25-35 Aggregates Say ‘NO’ to Long-Term Potentiation in the Hippocampus through Activation of Stress-Induced Phosphatase 1 and Mitochondrial Na+/Ca2+ Exchanger