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.

/pdf/a-robust-and-high-throughput-cre-reporting-and-4ytqviywww.pdf

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.

/pdf/genome-wide-atlas-of-gene-expression-in-the-adult-mouse-2j5ql1rdgm.pdf

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.

/pdf/the-free-energy-principle-a-unified-brain-theory-3vz1twg7nv.pdf

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...

/pdf/short-term-synaptic-plasticity-5d4dx79319.pdf

Short-Term Synaptic Plasticity

Clonidine and cortical plasticity: possible evidence for noradrenergic involvement.

Author response: Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain

Intracortical synapses exhibit several forms of short-term plasticity that cause synaptic efficacy at any given time to depend on the previous history of presynaptic activity. We have measured synaptic transmission between layer 4 and layer 2/3 in slices of rat visual cortex and used the data to construct an accurate mathematical description of intracortical short-term synaptic plasticity. These data show rapid synaptic facilitation and three forms of synaptic depression differing in their rates of onset and recovery. The dominant effect seen is overall synaptic depression that causes steady-state synaptic efficacy to decrease as a function of presynaptic firing rate. At high rates, the steady-state efficacy is inversely proportional to firing rate which implies that cortical synapses do not convey information about the magnitude of sustained high firing rates. However, this same dependence means that, for transient signals, synapses convey information about fractional rather than absolute changes in presynaptic firing rates. We explore the functional significance of this result including its implications for spike-rate adaptation and mechanisms that produce directional selectivity in visually responsive neurons.

Functional signatificance of synaptic depression between cortical neurons

In a brainstem auditory nucleus, excitatory synapses from the same presynaptic neuron are shown to cause opposing forms of spike timing–dependent plasticity in projection neurons and GABAergic interneurons at low frequencies, but to cause the same form of plasticity at high frequencies. The net effect is to enhance activation of the projection neurons by relevant stimuli.

Hebb and anti-Hebb meet in the brainstem.

Provided herein are approaches for the detection, identification, and/or selective amplification of specific target species or target variants of nucleic acid sequences, even within an excess of unwanted similar sequences or variants. These approaches include methods, assays, and kits for suppression PCR that require, in part, DNA polymerase that lacks 5′-3′ exonuclease activity, and a PCR primer, termed a forward selective primer or a nunchaku primer. The methods, assays, and kits provided herein are useful for a wide variety of applications, including cancer screening assays and kits, personalized screening assays, SNP (single nucleotide polymorphism) genotyping and identification, and downstream applications such as next generation high-throughput genomic sequencing and library construction.

Sacha B. Nelson

Papers

Clonidine and cortical plasticity: possible evidence for noradrenergic involvement.

Author response: Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain

Functional signatificance of synaptic depression between cortical neurons

Hebb and anti-Hebb meet in the brainstem.

Methods for suppression pcr