Volume 16 Issue 7, July 2013

Chaotic networks produce rich temporal dynamics that could be useful for timing, but are extremely sensitive to perturbations. Work now shows that a learning rule for the weights of a chaotic recurrent network can stabilize time-varying activity patterns. This result can be used to train output units to produce generic timed responses.

Chesi et al. use exome sequencing of trios consisting of subjects with amyotrophic lateral sclerosis and their parents to find de novo variants in 25 genes, one of which is the chromatin regulator SS18L1 (CREST).

Little is known about the molecular and cellular mechanisms underlying acute and chronic itch. A new technique for silencing peripheral itch neurons defines two independent itch circuits that transmit signals to the CNS.

Modern theories of associative learning center on a prediction error. A study finds that artificial activation of dopamine neurons can substitute for missing reward prediction errors to rescue blocked learning.

The use of patient-derived stem cells for in vitro neurodegenerative disease modeling has gained much traction in recent years. In this review, the authors examine the potential caveats and pitfalls of stem cell use and highlight insights from the literature that suggest methods for overcoming these difficulties.

Standard light microscopy techniques cannot resolve the subcellular structures of neurons: axons, presynaptic active zones, postsynaptic densities and dendritic spines. In this review, the authors discuss the use of recently developed super-resolution light microscopic techniques to resolve these structures, and how such techniques can be most effectively used in the future.

Immunogold techniques allow target proteins to be localized subcellularly quantitatively and with high precision. In this review, the authors discuss applications of these techniques, as well as limitations and possible pitfalls to be avoided in their use.

The strength and versatility of optogenetics rely not only on the diversity of the optogene toolkit but also on the ability to achieve spatially selective and temporally precise control of electrical activity in specific neural circuits, individual cells or subcellular compartments. This remains a challenge and requires sophisticated experimental designs. In this article, Packer, Roska and Häusser discuss the myriad combinations of optical, anatomical and genetic strategies that can be used to manipulate neuronal activity with light.

This review discusses recent advances in optogenetic pharmacology, discussing its potential to manipulate endogenous neuronal signaling proteins. These approaches include caged agonists and antagonists and reversibly photoswitchable ligands.

In this review article, the authors give a brief overview of the sensory capabilities of rodents and of their cortical areas devoted to sensation and decision. They also review methods of psychophysics, focusing on the technical issues that arise in their implementation in rodents.

The authors review recent work using functional connectivity in fMRI and discuss the issues that constrain the interpretation of these studies, as well as the potential uses of this analysis technique.

The authors provide an overview of the uses and limitations of noninvasive brain stimulation techniques such as transcranial magnetic stimulation and suggest ways to advance the field.

Ependymal cell cilia regulate cerebrospinal fluid flow through the cerebral ventricles. Here the authors show that the metabolic peptide melanin-concentrating hormone (MCH) increases cilia beat frequency in the third ventricle, and a lack of the MCH receptor increases ventricle size.

Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology.

Exome sequencing of 47 ALS trios (patients and their unaffected parents) identified de novo mutations, including a mutation in the neuronal chromatin remodeling complex component, SS18L1. SS18L1 interacted with the ALS protein FUS, and mutation of SS18L1 in primary neurons resulted in impaired neurite outgrowth.

The calyx of Held synapse in the auditory brainstem is an unusually large and fast synapse. Using genome-wide screening and conditional deletion in mice, Xiao and colleagues identify BMP signaling as a crucial factor in the development of the functional and structural properties of this large central synapse.

The authors show that the TNFα receptor, expressed on peripheral target tissue, can act as a ligand to induce reverse TNFα signaling in superior cervical ganglion neurons, promoting neurite growth and branching. This reverse signaling is crucial in establishing sympathetic innervation.

In this paper, Korb and colleagues find that Arc can shuttle in and out of the nucleus in an activity-dependent manner. The authors further demonstrate that the nuclear translocation of Arc participates in homeostatic plasticity by promoting the formation of PML nuclear bodies, which in turn decreases GluA1 transcription, eventually contributing to the downscaling of synaptic strength.

The authors identify a hemispheric asymmetry in neurogenesis in adult zebrafish. This asymmetry could be reversed by olfactory sensory deprivation or decreasing Notch signaling on the left side. Behavioral responses of fish to olfactory cues depended on the left olfactory epithelium, which may be a result of this asymmetry in neurogenesis.

The authors use high-throughput histology to construct three-dimensional maps of the vascular architecture throughout mouse vibrissal cortex. Modeling of the vascular networks revealed that microvessels are highly interconnected; do not form functional 'modules', as previously suggested; and lead to flow patterns that explain the origin of single vessel strokes.

In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome–causing mutations in the C-terminal domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 missense mutations exhibit severe motor phenotypes.

The authors use two-photon calcium imaging, EEG and electrophysiology to study ensemble neuronal activity in genetically altered mice that lack the Fmr1 protein: a model of Fragile X syndrome. Unanesthetized Fmr1^−/− mice showed high synchrony of neocortical network activity and higher firing rates during sleep.

In this study, the authors use selective silencing of specific subsets of afferent neurons and stimulation with pruritogens or algogens to show that histaminergic and non-histaminergic itch is mediated by functionally distinct sets of sensory fibers. These findings provide further evidence for the labeled line theory of sensory perception.

The authors show that mating-induced partner preference in monogamous prairie voles is associated with increased histone acetylation at the oxytocin and vasopressin V1a receptor promoters, and subsequent upregulation of these genes. Histone deacetylase inhibitors induced partner preference in females even in the absence of mating.

Here the authors describe a recurrent neural network model that tells time on the order of seconds and generates complex spatiotemporal motor patterns in the presence of high levels of noise. Robustness is achieved through the tuning of the recurrent connections, which produces stable patterns in the face of perturbations.

Imaging calcium and vesicular release from thousands of synapses during contrast adaptation, Nikolaev and colleagues reveal the stratified organization of depressing and facilitating bipolar cells terminals in the zebrafish retina. The study also offers some insights into the cellular and circuit mechanisms of bidirectional gain modulation in this sensory system.

Using a combination of computational modeling and electrophysiological recordings, the authors show that the dynamics of spike-frequency adaptation have the effect of temporally decorrelating incoming signals. This decorrelation makes for more energy-efficient information transfer in the CNS.

Odors evoke complex spatiotemporal patterns of activity in the olfactory bulb. The authors show that the spike rates of downstream piriform cortex neurons (PCNs) reflect the relative timing of activation. Posterior PCNs are more sensitive to input timing than anterior PCNs.

The authors use mouse behavior, electrophysiology and optogenetics to dissect the temporal interactions between whisker movement, neural activity and sensation of touch. Their results suggest that mice integrate coding of touch with movement over timescales of a whisking bout to produce perception of active touch.

Unexpected rewards activate midbrain dopamine neurons, and this response is proposed to support learning by signaling discrepancies between actual and expected outcomes. Here the authors use optogenetic stimulation to demonstrate a causal role for temporally precise dopamine neuron signaling in cue-reward learning.

The authors examined neuronal responses in V1 and V2 to synthetic texture stimuli that replicate higher-order statistical dependencies found in natural images. V2, but not V1, responded differentially to these textures, in both macaque (single neurons) and human (fMRI). Human detection of naturalistic structure in the same images was predicted by V2 responses, suggesting a role for V2 in representing natural image structure.

Technology has expanded horizons in a wide range of scientific fields and neuroscience is No. exception. In the past five years, the number of abstracts describing new methods or technology development that were presented at the annual Society for Neuroscience meeting increased by nearly 50 percent. As neuroscientists capitalize on recent technological innovations, they stand poised to make unprecedented progress. In this issue, we present an array of review articles sampling some of the most exciting recent advances in techniques used across the field of neuroscience.