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

The Disease Progression of Mecp2 Mutant Mice Is Affected by the Level of BDNF Expression

Identifying the neuronal cell types that comprise the mammalian forebrain is a central unsolved problem in neuroscience. Global gene expression profiles offer a potentially unbiased way to assess functional relationships between neurons. Here, we carried out microarray analysis of 12 populations of neurons in the adult mouse forebrain. Five of these populations were chosen from cingulate cortex and included several subtypes of GABAergic interneurons and pyramidal neurons. The remaining seven were derived from the somatosensory cortex, hippocampus, amygdala and thalamus. Using these expression profiles, we were able to construct a taxonomic tree that reflected the expected major relationships between these populations, such as the distinction between cortical interneurons and projection neurons. The taxonomic tree indicated highly heterogeneous gene expression even within a single region. This dataset should be useful for the classification of unknown neuronal subtypes, the investigation of specifically expressed genes and the genetic manipulation of specific neuronal circuit elements.

Molecular taxonomy of major neuronal classes in the adult mouse forebrain

https://vision.ustc.edu.cn/papers/Short-Term%20Depression%20at%20Thalamocortical%20Synapses%20Contributes%20to%20Rapid%20Adaptation%20of%20Cortical%20Sensory%20Responses%20In%20Vivo.pdf

Short-Term Depression at Thalamocortical Synapses Contributes to Rapid Adaptation of Cortical Sensory Responses In Vivo

https://www.cell.com/neuron/pdf/S0896-6273(00)80563-2.pdf

BDNF Has Opposite Effects on the Quantal Amplitude of Pyramidal Neuron and Interneuron Excitatory Synapses

Visual deprivation during a developmental sensitive period markedly alters visual cortical response properties, but the changes in intracortical circuitry that underlie these effects are poorly understood. Here we use a slice preparation of rat primary visual cortex to show that 2 d of prior visual deprivation early in life increases the excitability of layer 4 circuitry. Slice recordings showed that spontaneous activity of layer 4 star pyramidal neurons increased 25-fold after 2 d of visual deprivation between postnatal days (P) 15 and P17. This effect was mediated by increased net excitatory and decreased net inhibitory synaptic drive. Paired recordings showed that excitatory connections between star pyramidal neurons doubled in amplitude, whereas inhibitory connections decreased or increased depending on the interneuron class. These effects reversed when vision was restored. This dynamic adjustment of the excitation-inhibition balance may allow the networks within layer 4 to maintain stable levels of activity in the face of variable sensory input.

Sacha B. Nelson

Papers

The Disease Progression of Mecp2 Mutant Mice Is Affected by the Level of BDNF Expression

Molecular taxonomy of major neuronal classes in the adult mouse forebrain

Short-Term Depression at Thalamocortical Synapses Contributes to Rapid Adaptation of Cortical Sensory Responses In Vivo

BDNF Has Opposite Effects on the Quantal Amplitude of Pyramidal Neuron and Interneuron Excitatory Synapses

Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation.