Calcium Dynamics in Basal Dendrites of Layer 5A and 5B Pyramidal Neurons Is Tuned to the Cell-Type Specific Physiological Action Potential Discharge

Layer 5 (L5) is a major neocortical output layer containing L5A slender-tufted (L5A-st) and L5B thick-tufted (L5B-tt) pyramidal neurons. These neuron types differ in their in vivo firing patterns, connectivity and dendritic morphology amongst other features, reflecting their specific functional role within the neocortical circuits. Here, we asked whether the active properties of the basal dendrites that receive the great majority of synaptic inputs within L5 differ between these two pyramidal neuron classes. To quantify their active properties, we measured the efficacy with which action potential (AP) firing patterns backpropagate along the basal dendrites by measuring the accompanying calcium transients using two-photon laser scanning microscopy in rat somatosensory cortex slices. For these measurements we used both “artificial” three-AP patterns and more complex physiological AP patterns that were previously recorded in anesthetized rats in L5A-st and L5B-tt neurons in response to whisker stimulation. We show that AP patterns with relatively few APs (3APs) evoke a calcium response in L5B-tt, but not L5A-st, that is dependent on the temporal pattern of the three APs. With more complex in vivo recorded AP patterns, the average calcium response was similar in the proximal dendrites but with a decay along dendrites (measured up to 100 μm) of L5B-tt but not L5A-st neurons. Interestingly however, the whisker evoked AP patterns—although very different for the two cell types—evoke similar calcium responses. In conclusion, although the effectiveness with which different AP patterns evoke calcium transients vary between L5A-st and L5B-tt cell, the calcium influx appears to be tuned such that whisker-evoked calcium transients are within the same dynamic range for both cell types

The impact of neuron morphology on cortical network architecture

The neurons in the cerebral cortex are not randomly interconnected. This specificity in wiring can result from synapse formation mechanisms that connect neurons, depending on their electrical activity and genetically defined identity. Here, we report that the morphological properties of the neurons provide an additional prominent source by which wiring specificity emerges in cortical networks. This morphologically determined wiring specificity reflects similarities between the neurons’ axo-dendritic projections patterns, the packing density, and the cellular diversity of the neuropil. The higher these three factors are, the more recurrent is the topology of the network. Conversely, the lower these factors are, the more feedforward is the network’s topology. These principles predict the empirically observed occurrences of clusters of synapses, cell type-specific connectivity patterns, and nonrandom network motifs. Thus, we demonstrate that wiring specificity emerges in the cerebral cortex at subcellular, cellular, and network scales from the specific morphological properties of its neuronal constituents

former title: A theory for the emergence of neocortical network architecture

Developmental programs that guide neurons and their neurites into specific subvolumes of the mammalian neocortex give rise to lifelong constraints for the formation of synaptic connections. To what degree do these constraints affect cortical wiring diagrams? Here we introduce an inverse modeling approach to show how cortical networks would appear if they were solely due to the spatial distributions of neurons and neurites. We find that neurite packing density and morphological diversity will inevitably translate into non-random pairwise and higher-order connectivity statistics. More importantly, we show that these non-random wiring properties are not arbitrary, but instead reflect the specific structural organization of the underlying neuropil. Our predictions are consistent with the empirically observed wiring specificity from subcellular to network scales. Thus, independent from learning and genetically encoded wiring rules, many of the properties that define the neocortex’ characteristic network architecture may emerge as a result of neuron and neurite development

Synthesis of triazole-linked 2-trichloromethylquinazolines and exploration of their efficacy against P. falciparum

Using 2-trichloromethylquinazoline as scaffold, seven novel triazole-linked compounds have been synthesized using CuAAC chemistry. The in vitrobiological activity of four of the compounds on the Plasmodium falciparumchloroquine-sensitive strain NF54 was then determined. The compounds which were tested showed moderate activity with 1.45 /iM as the lowest inhibitory concentration

Nuclear medium modifications of the NN interaction via quasielastic (p⃗,p⃗′\vec p,\vec p ') and (p⃗,n⃗\vec{p},\vec{n}) scattering

Within the relativistic PWIA, spin observables have been recalculated for quasielastic ($\vec p,\vec p '$) and ($\vec p,\vec n$) reactions on a $^{40}$Ca target. The incident proton energy ranges from 135 to 300 MeV while the transferred momentum is kept fixed at 1.97 fm^{-1}. In the present calculations, new Horowitz-Love--Franey relativistic NN amplitudes have been generated in order to yield improved and more quantitative spin observable values than before. The sensitivities of the various spin observables to the NN interaction parameters, such as (1) the presence of the surrounding nuclear medium, (2) a pseudoscalar versus a pseudovector interaction term, and (3) exchange effects, point to spin observables which should preferably be measured at certain laboratory proton energies, in order to test current nuclear models. This study also shows that nuclear medium effects become more important at lower proton energies ($\leq$ 200 MeV). A comparison to the limited available data indicates that the relativistic parametrization of the NN scattering amplitudes in terms of only the five Fermi invariants (the SVPAT form) is questionable.Comment: 10 pages, 6 Postscript figures, uses psfig.sty and article.sty, submitted to Phys. Rev.

Boson-fermion mapping and dynamical supersymmetry in fermion models

We show that a dynamical supersymmetry can appear in a purely fermionic system. This ``supersymmetry without bosons" is constructed by application of a recently introduced boson-fermion Dyson mapping from a fermion space to a space comprised of collective bosons and ideal fermions. In some algebraic fermion models of nuclear structure, particular Hamiltonians may lead to collective spectra of even and odd nuclei that can be unified using the dynamical supersymmetry concept with Pauli correlations exactly taken into account.Comment: 20 pages. Revtex. One PostScript figure available on request from P

Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain

Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.5 mV, interquartile range 0.4–1.0 mV) with most variability associated with the cell-type specific connection studied (min 0.1–max 1.4 mV), (2) synaptic function cannot be generalized across human and rodent, which we exemplify by discussing the differences in anatomical and functional properties of pyramidal-to-pyramidal connections within human and rodent cortical layers 2 and 3. With only a handful of studies available on synaptic transmission in human, it is obvious that much remains unknown to date. Uncovering the shared and divergent principles of synaptic transmission across species however, will almost certainly be a pivotal step toward understanding human cognitive ability and brain function in health and disease

The development of a toxicity database using freshwater macroinvertebrates, and its application to the protection of South African water resources

There is a growing international trend towards the protection of freshwater resources from pollution by imposing instream guidelines and specified waste-discharge conditions. Current methods for devising freshwater quality guidelines are based on species sensitivity distributions (SSDs) that are used to identify pollutant concentrations, ensuring the protection of a modelled percentage of species (95% protection is a common goal). SSDs are derived from the toxicity test results of as many taxa as possible for each polluting substance. Waste-discharge licences can be for single substances, specified in terms of chemical concentrations, and derived in conjunction with instream guidelines; or for complex mixtures, specified in terms of toxic units. In both cases toxicity test results are the core data used. The emphasis on SSDs calls into question the species constituting the test populations. It is likely that SSDs based in part on the responses of local organisms will achieve superior site-specific ecological protection. Until the early 1990s, there were very few data on the tolerances of South African freshwater organisms. In the intervening decade, the Unilever Centre for Environmental Water Quality at Rhodes University has developed a toxicity database that, to date, records the responses of 21 South African freshwater taxa to 26 single-substance pollutants or mixtures. This is the most comprehensive database of South African toxicity responses available and has been used in the drawing up of methods and guidelines to protect water resources. This paper aims to make these data available and to describe applications of the data using selected case studies