Neural Population Structures and Consequences for Neural Coding

Researchers studying neural coding have speculated that populations of neurons would more effectively represent the stimulus if the neurons "cooperated:" by interacting through lateral connections, the neurons would process and represent information better than if they functioned independently. We apply our new theory of information processing to determine the fidelity limits of simple population structures to encode stimulus features. We focus on noncooperative populations, which have no lateral connections. We show that they always exhibit positively correlated responses and that as population size increases, they perfectly represent the information conveyed by their inputs regardless of the individual neuron's coding scheme. Cooperative populations, which do have lateral connections, can, depending on the nature of the connections, perform better or worse than their noncooperative counterparts. We further show that common notions of synergy fail to capture the level of cooperation and to reflect the information processing properties of populations.     

Information-Theoretic Analysis of Neural Coding

We describe an approach to analyzing single- and multiunit (ensemble) discharge patterns based on information-theoretic distance measures and on empirical theories derived from work in universal signal processing. In this approach, we quantify the difference between response patterns, whether time-varying or not, using information-theoretic distance measures. We apply these techniques to single- and multiple-unit processing of sound amplitude and sound location. These examples illustrate that neurons can simultaneously represent at least two kinds of information with different levels of fidelity. The fidelity can persist through a transient and a subsequent steady-state response, indicating that it is possible for an evolving neural code to represent information with constant fidelity.     

Diversity in ABC transporters: Type I,II and III importers

Abstract

ATP-binding cassette transporters are multi-subunit membrane pumps that transport substrates across membranes. While significant in the transport process, transporter architecture exhibits a range of diversity that we are only beginning to recognize. This divergence may provide insight into the mechanisms of substrate transport and homeostasis. Until recently, ABC importers have been classified into two types, but with the emergence of energy-coupling factor (ECF) transporters there are potentially three types of ABC importers. In this review, we summarize an expansive body of research on the three types of importers with an emphasis on the basics that underlie ABC importers, such as structure, subunit composition and mechanism.     

Role of mitochondrial DNA in diabetes Mellitus Type I and Type II

Morbidity and mortality from diabetes mellitus and associated illnesses is a major problem across the globe. Anti-diabetic medicines must be improved despite existing breakthroughs in treatment approaches. Diabetes has been linked to mitochondrial dysfunction. As a result, particular mitochondrial diabetes kinds like MIDD (maternally inherited diabetes & deafness) and DAD (diabetic autonomic dysfunction) have been identified and studied (diabetes and Deafness). Some mutations as in mitochondrial DNA (mtDNA), that encodes for a significant portion of mitochondrial proteins as well as mitochondrial tRNA essential for mitochondrial protein biosynthesis, are responsible for hereditary mitochondrial diseases. Tissue-specificity and heteroplasmy have a role in the harmful phenotype of mtDNA mutations, making it difficult to generalise findings from one study to another. There are a huge increase in the number for mtDNA mutations related with human illnesses that have been identified using current sequencing technologies. In this study, we make a list on mtDNA mutations linked with diseases and diabetic illnesses and explore the methods by which they contribute to the pathology's emergence.     

神经元放电阈值的可变性及其意义

神经元能够将不同时空模式的突触输入转化为时序精确的动作电位输出，这种灵活、可靠的信息编码方式是神经集群在动态环境或特定任务下产生所需活动模式的重要基础。动作电位的产生遵循全或无规律，只有当细胞膜电压达到放电阈值时，神经元才产生动作电位。放电阈值在细胞内和细胞间具有高度可变性，具体动态依赖于刺激输入和放电历史。特别是，放电阈值对动作电位起始前的膜电压变化十分敏感，这种状态依赖性产生的生物物理根源包括Na⁺失活和K⁺激活。在绝大多数神经元中，动作电位的触发位置是轴突起始端，这个位置处的阈值可变性是决定神经元对时空输入转化规律的关键因素。但是，电生理实验中动作电位的记录位置却通常是胞体或近端树突，此处的阈值可变性高于轴突起始端，而其产生的重要根源是轴突动作电位的反向传播。基于胞体测量的相关研究显示，放电阈值动态能够增强神经元的时间编码、特征选择、增益调控和同时侦测能力。本文首先介绍放电阈值的概念及量化方法，然后详细梳理近年来国内外关于放电阈值可变性及产生根源的研究进展，在此基础上归纳总结放电阈值可变性对神经元编码的重要性，最后对未来放电阈值的研究方向进行展望。     

Distribution of carotid body type I cells and other periadventitial type I cells in the carotid bifurcation regions of the rabbit

Summary The distribution of carotid body type I and periadventitial type I cells in the carotid bifurcation regions was investigated unilaterally in seven and bilaterally in two New Zealand White rabbits. Carotid body type I cells occurred in close proximity to the wall of the internal carotid artery immediately rostral to the carotid bifurcation, within a division of connective tissue with defineable but irregular borders. Caudally, and separate from the main mass of carotid body type I cells, isolated groups of periadventitial type I cells lay freely in the connective tissue around the internal carotid artery and alongside the carotid bifurcation and common carotid artery. A overall picture of the carotid body in the rabbit was reconstructed and the occurrence and significance of periadventitial type I cells discussed.The authors are indebted to Mr. Stephen Jones of the Department of Histopathology, St Bartholomew's Hospital, for expert assistance in the preparation of the material, and to Mr. A.J. Aldrich of the Department of Anatomy for photography. This work was supported by a grant from the Wellcome Trust to one of us (M. de B.D.)     

Dendritic Integration in Olfactory Sensory Neurons: A Steady-State Analysis of How the Neuron Structure and Neuron Environment Influence the Coding of Odor Intensity

Response properties of the receptor potential at steady state were analyzed in a biophysical model of an olfactory sensory neuron embedded in a multicell environment. The neuron structure was described as a set of several identical dendrites (or cilia) bearing the transduction mechanisms, joined to a nonsensory part—dendritic knob, soma, and axon. The different ionic compositions of the media surrounding the neuron sensory and nonsensory parts and the extraneuronal voltage sources, which both result from the presence of auxiliary cells, were also taken into account. Analytical solutions were found to describe how the receptor potential at the nonsensory part responds to a uniform change in the odorant-dependent conductance resulting from odorant stimulation of the sensory dendrites. We investigated the influence of various geometrical and electrical parameters on the receptor-potential response in the classical model neuron within a homogeneous environment and in the model neuron surrounded with auxiliary cells. First, it was found that the maximum amplitude of the receptor potential is independent of the neuron structure in the absence of auxiliary cells but not in their presence. In the latter case, the amplitude decreases with the length and number of sensory dendrites and with the input resistance of the nonsensory part. Second, the sensitivity (as measured by the increase in membrane conductance at half-maximum response) of the neuron model in the absence of auxiliary cells is higher, but its dynamic range is narrower than in their presence. The dynamic range is wide and the sensitivity low when the input resistance of the nonsensory part is small and the sensory dendrite is unbranched. Both sensitivity and dynamic range are higher for a longer dendrite. These results help understand the morphology of insect olfactory sensilla and can be generalized to other neuron types.     

SK channel subtypes enable parallel optimized coding of behaviorally relevant stimulus attributes: A review

Ion channels play essential roles toward determining how neurons respond to sensory input to mediate perception and behavior. Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and have been extensively characterized both molecularly and physiologically in terms of structure and function. It is clear that SK channels are key determinants of neural excitability as they mediate important neuronal response properties such as spike frequency adaptation. However, the functional roles of the different known SK channel subtypes are not well understood. Here we review recent evidence from the electrosensory system of weakly electric fish suggesting that the function of different SK channel subtypes is to optimize the processing of independent but behaviorally relevant stimulus attributes. Indeed, natural sensory stimuli frequently consist of a fast time-varying waveform (i.e., the carrier) whose amplitude (i.e., the envelope) varies slowly and independently. We first review evidence showing how somatic SK2 channels mediate tuning and responses to carrier waveforms. We then review evidence showing how dendritic SK1 channels instead determine tuning and optimize responses to envelope waveforms based on their statistics as found in the organism's natural environment in an independent fashion. The high degree of functional homology between SK channels in electric fish and their mammalian orthologs, as well as the many important parallels between the electrosensory system and the mammalian visual, auditory, and vestibular systems, suggest that these functional roles are conserved across systems and species.     

Membrane Resonance and Stochastic Resonance Modulate Firing Patterns of Thalamocortical Neurons

We examined the interactions of subthreshold membrane resonance and stochastic resonance using whole-cell patch clamp recordings in thalamocortical neurons of rat brain slices, as well as with a Hodgkin-Huxley-type mathematical model of thalamocortical neurons. The neurons exhibited the subthreshold resonance when stimulated with small amplitude sine wave currents of varying frequency, and stochastic resonance when noise was added to sine wave inputs. Stochastic resonance was manifest as a maximum in signal-to-noise ratio of output response to subthreshold periodic input combined with noise. Stochastic resonance in conjunction with subthreshold resonance resulted in action potential patterns that showed frequency selectivity for periodic inputs. Stochastic resonance was maximal near subthreshold resonance frequency and a high noise level was required for detection of high frequency signals. We speculate that combined membrane and stochastic resonances have physiological utility in coupling synaptic activity to preferred firing frequency and in network synchronization under noise.     

Distribution of excitation energy among photosystem I and photosystem II in red algae. I. Action spectra of light reactions I and II

Action spectra of light reaction I and light reaction II from red algae (marine members of Florideae and Bangiales) were measured with 550 nm (light 2) or 699 nm (light 1) background light, using a Teflon-covered platinum electrode for O₂ measurement. Care was taken to ensure that maximum enhancement was reached by the background light.The action spectra of light reaction I, we found under these conditions, are very similar to the thallus absorption, whilst the action spectra of light reaction II show, besides strong bands of the phycobilins, only minor bands of chlorophyll a, which account for only 10–20% of the total chlorophyll.The spectra are discussed on the basis of two main types of models of energy distribution over both photosynthetic systems. If this distribution is considered to be invariable (models 1a and b), one has to assume that almost exactly half of the total chlorophyll is not involved in the supply of the non-cyclic electron transport with excitation energy. This part, however, has to be thought of as incorporated in the thylakoid membrane in a similar manner to the chlorophyll in photosystem I. However, if one supposes an almost complete equilibration in the energy distribution over both systems as long as the primary absorption in photosystem II prevails (models 2a and b), there is no need for the assumption of such photosynthetically ‘inactive’ or less active chlorophyll. Some evidence is shown that strongly supports model 2.     

The crystal and molecular structures of cellulose I and II

The paper describes molecular dynamics (MD) simulations on the crystal structures of the Iβ and II phases of cellulose. Structural proposals for each of these were made in the 1970s on the basis of X-ray diffraction data. However, due to the limited resolution of these data some controversies remained and details on hydrogen bonding could not be directly obtained. In contrast to structure factor amplitudes in X-ray diffraction, energies, as obtained from MD simulations, are very sensitive to the positions of the hydroxyl hydrogen atoms. Therefore the latter technique is very suitable for obtaining such structural details. MD simulations of the Iβ phase clearly shows preference for one of the two possible models in which the chains are packed in a parallel orientation. Only the parallel-down mode (in the definition of Gardner and Blackwell (1974) J Biopolym 13: 1975-2001) presents a stable structure. The hydrogen bonding consists of two intramolecular hydrogen bonds parallel to the glycosidic linkage for both chains, and two intralayer hydrogen bonds. The layers are packed hydrophobically. All hydroxymethyl group are positioned in the tg conformation. For the cellulose II form it was found that, in contrast to what seemed to emerge from the X-ray fibre diffraction data, both independent chains had the gt conformation. This idea already existed because of elastic moduli calculations and 13C-solid state NMR data. Recently, the structure of cellotetraose was determined. There appear to be a striking similarity between the structure obtained from the MD simulations and this cellotetraose structure in terms of packing of the two independent molecules, the hydrogen bonding network and the conformations of the hydroxymethyl group, which were also gt for both molecules. The structure forms a 3D hydrogen bonded network, and the contribution from electrostatics to the packing is more pronounced than in case of the Iβ structure. In contrast to what is expected, in view of the irreversible transition of the cellulose I to II form, the energies of the Iβ form is found to be lower than that of II by 1 kcal mol-1 per cellobiose. This revised version was published online in November 2006 with corrections to the Cover Date.     

Power, precaution, Type II error and sampling design in assessment of environmental impacts

Increasingly, environmental managers attempt to incorporate precautionary principles into decision making. In any quantitative analysis of impacts, precaution is closely related to the power of the analysis to detect an impact. Designs of sampling to detect impacts are, however, complex because of natural spatial and temporal variability and the intrinsic nature of the statistical interactions which define impacts. Here, pulse and press responses and impacts that affect time courses (temporal variance) were modelled to determine the influences of increasing temporal replication—sampling more times in each of several longer periods before and again after an impact.Increasing the number of control or reference locations and number of replicate sample units at each time and place of sampling investigated the influence of spatial replication on power. From numerous scenarios of impacts, with or without natural spatial and temporal interactions (i.e. not caused by an impact), general recommendations are possible. Detecting press impacts requires maximal numbers of control locations. Shorter-term pulse impacts are best detected when the number of periods sampled is maximized. Impacts causing changes in temporal variance are most likely to be detected by sampling with the greatest possible number of periods or times within periods.To allow precautionary decision making, the type of predicted impact should be specified with its magnitude and duration. Only then can sampling be designed to be powerful, thereby allowing precautionary concepts to be invoked.     

Immunochemical Analysis of Discoidins I and II at the Cell Surface in Wild Type and Aggregation-Defective Mutants of Dictyostelium discoideum

The endogenous lectins discoidins I and II are believed to be primary components of the morphogenetic cell cohesion system of D discoideum. We have developed two immunochemical methods to analyze the association of the discoidins with the cell surface. One method is a two-stage specific antibody binding assay in which intact cells are incubated on ice with rabbit serum (either control serum or antidiscoidin I and II), washed, then incubated with ¹²⁵I-Protein A. Specific antibody binding is defined as the difference between percent radioactivity bound with antidiscoidin versus control serum during the first stage. Substantial specific binding was observed with developed A3 cells but not with vegetative cells, and nearly all of the activity could be removed by pread-sorption of the antiserum with discoidin-Sepharose. As a complementary method, quantitative immunoadsorption analysis was performed in which we tested the ability of intact cells to remove antibodies reactive with purified ¹²⁵I-discoidin I or II. Developed cells, but not vegetative cells, were capable of adsorbing antibodies reactive with discoidin I as well as those reactive with discoidin II. This represents the first demonstration that both lectins are present on the surface of cohesive cells. These procedures, coupled with other methods to analyze soluble discoidin in cell extracts, were used to study discoidin expression in wild type cells and in two newly isolated aggregation-defective mutants. Strain EB-32 fails to aggregate and displays little or no discoidin in cell extracts or at the cell surface. On the other hand, strain EB-18 forms loose amorphous mounds, and expresses substantial quantities of the discoidins, both in cell extracts and at the cell surface. These mutants should prove valuable in studying the organization and regulation of discoidins I and II at the surface of aggregating cells.     

Presence of neurophysins I and II in the human pineal gland: Comparison with the content of neurohypophyseal hormones

We have previously measured the individual content of immunoreactive vasopressin (AVP), oxytocin (OT) and vasotocin (AVT) in 155 human pineal glands, and report here identification and measurement of the neurophysin (Np) content of the same glands, using specific homologous human neurophysin I (HNp I) and neurophysin II (HNp II) radioimmunoassays. Median values for HNp I were for men 47 ng/gland (range, 5 to 1360) and for women 24 ng/gland (range, 5 to 1000); median values for HNp II were respectively 7 ng/gland (range, 2 to 191) and 15 ng/gland (range, 2 to 356) with no significant difference between men and women for HNp I and HNp II but a significant difference (p<0.001) between HNp I and HNp II for both sexes. Gel filtration showed that pineal neurophysins were eluted at the same volume as both standard Np and Np from human posthypophyses used as controls. HNp I correlated both with AVP (r_s=0.54 for men and 0.55 for women) and OT (r_s=0.86 for men and 0.57 for women) but not with AVT, while HNp II correlated with AVP (r_s=0.52 for men and 0.53 for women) and OT (r_s=0.92 for men and 0.50 for women) but not with AVT. This study thus confirms the presence of two neurophysins in the human pineal gland and further indicates that they are related to AVP and OT concentrations in the same gland. The results also imply, however, that the presence of immunoreactive AVT (more probably a closely related peptide) is independent of the neurophysins.     

Comparison of the changes in mushroom (Agaricus bisporus) compost during windrow and bunker stages of phase I and II

The changes in thermophilic fungi and biochemical characteristics, during windrow and bunker stages of phase I and phase II composts, were compared in this investigation. Composts prepared by the two phase I systems differed in a number of key parameters including mean straw length, population of Scytalidium thermophilum, dry matter, conductivity, nitrogen dry matter, ammonia, fibre content and ash. S. thermophilum populations in phase I composts were significantly higher in windrow compared to bunker‐composted materials as a result of the larger high temperature (65‐80°C) core in bunker treatment, which inhibited microbial activity. Assessment of the composts for loss of matter during composting has revealed that the bunker system can conserve fresh matter better than the windrow production system, possibly due to lower microbial activities during bunker composting. The productivity of the phase II composts prepared from windrow and bunker systems was compared in trials using commercial growers.     

Functional interactions between the noncovalently associated N- and C-terminal halves of mammalian Type I hexokinase

The 100 kDa Type I isozyme of mammalian hexokinase has evolved by duplication and fusion of a gene encoding an ancestral 50 kDa hexokinase. Although the N- and C-terminal halves are similar in sequence, they differ in function, catalytic activity being associated only with the C-terminal half while the N-terminal half serves a regulatory role. The N- and C-terminal halves of rat Type I hexokinase have been coexpressed in M + R 42 cells. The halves associate noncovalently to produce a 100 kDa form that exhibits characteristics seen with the intact Type I isozyme but not with the isolated catalytic C-terminal half, i.e., characteristics that are influenced by interactions between the halves. These include a decreased K(m) for the substrate ATP and the ability of P(i) to antagonize inhibition by Glc-6-P or its analog, 1-5-anhydroglucitol-6-P. Thus, functional interactions between the N- and C-terminal halves do not require their covalent linkage.     

Type II restriction modification systems of Prevotella bryantii TC1-1 and Prevotella ruminicola 23 strains and their effect on the efficiency of DNA introduction via electroporation

The restriction endonucleases PbrTI and Pru2I, isoschizomers of Sau3AI and HaeIII, were partially purified and characterized from anaerobic rumen bacteria Prevotella bryantii TC1-1 and Prevotella ruminicola 23, respectively. These are the first type II restriction endonucleases discovered in strains of the genus Prevotella, and they represent one of the barriers hindering gene transfer in these microorganisms. Heterologous DNA was protected against the action of the PbrTI or Pru2I by incubation in a cell-free extract of the respective strain which contained 20 mM EDTA. This led to the development of a protocol enabling successful electrotransformation of the P. bryantii TC1-1 strain with a pRH3 Bacteroides--Escherichia coli shuttle vector containing up to 7-kb long DNA inserts. Plasmid DNA isolated from the transformed strain facilitated the transfer with further increased efficiency and made possible the introduction of ligation reaction products directly to P. bryantii TC1-1 without passing them first through E. coli.     

Regulation of MHC class I and II gene transcription: differences and similarities

Major histocompatibility complex (MHC) molecules serve as peptide receptors. These peptides are derived from processed cellular or extra-cellular antigens. The MHC gene complex encodes two major classes of molecules, MHC class I and class II, whose function is to present peptides to CD8⁺ (cytotoxic) and CD4⁺ (helper) T cells, respectively. The genes encoding both classes of MHC molecules seem to originate from a common ancestral gene. One of the hallmarks of the MHC is its extensive polymorphism which displays locus and allele-specific characteristics among the various MHC class I and class II genes. Because of its central role in immunosurveillance and in various disease states, the MHC is one of the best studied genetic systems. This review addresses several aspects of MHC class I and class II gene regulation in human and in particular, the contribution to the constitutive and cytokine-induced expression of MHC class I and II genes of MHC class-specific regulatory elements and regulatory elements which apparently are shared by the promoters of MHC class I and class II genes. Received: 12 January 1998     

Effects of dopaminergic compounds on carbonic anhydrase isozymes I,II, and VI

Studies on carbonic anhydrase (CA, EC 4.2.1.1) inhibitors have increased due to several therapeutic applications while there are few investigations on activators. Here we investigated CA inhibitory and activatory capacities of a series of dopaminergic compounds on human carbonic anhydrase (hCA) isozymes I, II, and VI. 2-Amino-1,2,3,4-tetrahydronaphthalene-6,7-diol hydrobromide and 2-amino-1,2,3,4-tetrahydronaphthalene-5,6-diol hydrobromide were found to show effective inhibitory action on hCA I and II whereas 2-amino-5,6-dibromoindan hydrobromide and 2-amino-5-bromoindan hydrobromide exhibited only moderate inhibition against both isoforms, being more effective inhibitors of hCA VI. K_i values of the molecules 3–6 were in the range of 41.12–363 μM against hCA I, of 0.381–470 μM against hCA II and of 0.578–1.152 μM against hCA VI, respectively. Compound 7 behaved as a CA activator with K_A values of 27.3 μM against hCA I, of 18.4 μM against hCA II and of 8.73 μM against hCA VI, respectively.