Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.

Complex brain networks: graph theoretical analysis of structural and functional systems

The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.

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A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

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Genome-wide atlas of gene expression in the adult mouse brain

A free-energy principle has been proposed recently that accounts for action, perception and learning. This Review looks at some key brain theories in the biological (for example, neural Darwinism) and physical (for example, information theory and optimal control theory) sciences from the free-energy perspective. Crucially, one key theme runs through each of these theories — optimization. Furthermore, if we look closely at what is optimized, the same quantity keeps emerging, namely value (expected reward, expected utility) or its complement, surprise (prediction error, expected cost). This is the quantity that is optimized under the free-energy principle, which suggests that several global brain theories might be unified within a free-energy framework.

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The free-energy principle: a unified brain theory?

▪ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca2+]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases...

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Short-Term Synaptic Plasticity

1 We studied the effect of varying excitatory and inhibitory drive on the N-methyl-D-aspartate (NMDA) receptor-mediated component of the visual responses of neurons in the cat dorsal lateral geniculate nucleus (dLGN) by varying the contrast and size of stimuli presented to the receptive fields of these cells 2 Cells were classified as either on- or off-center, X or Y, and lagged or nonlagged Stimulus contrast, and hence the amount of excitatory drive, was varied by changing the brightness of a spot, whose size and location matched the cell's receptive field center, relative to a fixed background luminance Responses to varying contrast were collected from each cell before, during, and after iontophoretic application of D-2-amino-5-phosphonovaleric acid (D-APV), a specific NMDA receptor antagonist From each contrast-response plot, a sigmoidal curve fit yielded five parameters on which we examined the effect of D-APV: the threshold contrast, saturation contrast, contrast at half saturation (C50), slope (gain) at C50, and saturation response 3 In most cells, application of D-APV reduced both the saturation response and the gain of the contrast-response curve, but did not reduce or change significantly the threshold contrast, saturation contrast, or C50 4 Cells varied in their sensitivity to D-APV, but for any given cell, the D-APV-sensitive component was nearly always a linear function of the control visual response level Thus, for a spot of optimal size, there was a constant proportion of the visual response attributable to NMDA receptors, regardless of the amplitude of the response 5 When the effect of D-APV on the visual responses to an optimal spot at varying contrasts was compared among different classes of dLGN cells, the visual responses of lagged X cells were reduced to a greater extent than those of either nonlagged X cells or the combined population of nonlagged X and Y cells 6 Stimulus size (spot diameter) was also varied systematically at a fixed contrast to vary the inhibitory drive to dLGN cells As stimulus size was increased, the response first increased because of increased stimulation of the receptive field center and then decreased because of increasing amounts of surround inhibition 7 The D-APV-sensitive component of individual cell responses was greater when the stimulus spot was less than or equal to optimal size than when the spot was larger Thus the contribution of NMDA receptors to the visual response decreased with increasing surround inhibition(ABSTRACT TRUNCATED AT 400 WORDS)

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Effect of stimulus contrast and size on NMDA receptor activity in cat lateral geniculate nucleus.

In the cerebral cortex of mammals, horizontal connections link cells up to several millimeters apart. In primary visual cortex (V1) of mammals with orientation maps, horizontal connections ramify in periodic patches across the cortical surface, connecting cells with similar orientation preferences. Rodents have orientation-selective cells but lack orientation maps, raising questions about relationships of horizontal connections to functional maps and receptive field properties. To address these questions, we studied anatomy of horizontal connections and characterized horizontal functional interactions in V1 of the gray squirrel, a highly visual rodent. Long-range intrinsic connections in squirrel V1 extended 1-2 mm but were not patchy or periodic. This result suggests that periodic and patchy connectivity is not a universal organizing principle of cortex, and the existence of patchy and periodic connectivity and functional maps may be linked. In multielectrode and intracellular recordings, we found evidence of unselective local interactions among cells, similar to pinwheel centers of carnivores. These data suggest that, in mammals with and without orientation maps, local connections link near neighbors without regard to orientation selectivity. In single-unit recordings, we found length-summing and end-stopped cells that were similar to those in other mammals. Length-summing cell surrounds were orientation selective, whereas surrounds of end-stopped cells were not. Receptive field response classes are quite similar across mammals, and therefore patchy and columnar connectivity may not be essential for these properties.

https://www.jneurosci.org/content/jneuro/26/29/7680.full.pdf

Lack of Patchy Horizontal Connectivity in Primary Visual Cortex of a Mammal without Orientation Maps

As first clearly demonstrated by the experiments of Wiesel and Hubel, the developing visual cortex is exquisitely sensitive to sensory deprivation. Temporary closure of one eye of a kitten during a critical period that extends from 3 weeks to 3 months of age results in a dramatic cortical reorganization such that most neurones, originally binocularly driven, are dominated exclusively by the open eye. Recently, attention has been directed to chemical factors which may influence the degree of plasticity during the critical period. The work of Kasamatsu and pettigrew suggests that cortical catecholamines, especially noradrenaline (NA), are essential for the normal plastic response to visual deprivation. In an effort to clarify the role of NA in visual cortical plasticity, we have monocularly deprived kittens whose cortex had been depleted of catecholamines by the neurotoxin 6-hydroxydopamine (6-OHDA). We used two strategies to deplete cortical NA: the first, pioneered by Kasamatsu el al., utilized osmotic minipumps to deliver 6-OHDA to visual cortex; the second involved systemic neonatal injections of 6-OHDA, a technique which has proved effective in rodents. We found, using high-pressure liquid chromatography (HPLC), that both techniques produced a substantial reduction in the level of cortical NA. However, single unit recording in area 17 revealed that the plastic response to monocular deprivation (MD) was only diminished in the kittens depleted by minipump.

Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity.

The gray squirrel (Sciurus carolinensis) is a diurnal highly visual rodent with a cone-rich retina. To determine which features of visual cortex are common to highly visual mammals and which are re...

https://www.physiology.org/doi/pdf/10.1152/jn.00106.2005

Sacha B. Nelson

Papers

Effect of stimulus contrast and size on NMDA receptor activity in cat lateral geniculate nucleus.

Lack of Patchy Horizontal Connectivity in Primary Visual Cortex of a Mammal without Orientation Maps

Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity.

Laminar Organization of Response Properties in Primary Visual Cortex of the Gray Squirrel (Sciurus carolinensis)

Cortical microcircuits: diverse or canonical?