Articles in 2014

A meeting of the academic and industry minds may help fuel the development of a new generation of CNS drugs.

The retina encodes visual information and sends it to the brain. We now learn that this neural code varies strongly with light adaptation. Does this mean a change in the message or a change in the way that the message is coded?

Loss of the receptor tyrosine kinase ErbB4 in somatostatin (SOM) inhibitory neurons of the thalamic reticular nucleus (TRN) enhances top-down cortical feedback, improving feature detection at the cost of reduced ability to switch attention. The study furthers our understanding of the circuit mechanisms underlying TRN function.

Single-unit recording in primate cortical area MT shows surprising sensitivity to depth defined by dynamical perspective cues. Depth might then be computed through recurrent circuits involving signals downstream of MT.

A study finds that formation of a cognitive map for a virtual reality environment demands associating specific movement trajectories with views to the constellation of peripheral landmarks.

In this technical report, Khodagholy and colleagues find that NeuroGrid, a planar, scalable and highly conformable electrode array, allows recordings of local-field potentials and stable single-unit activity from the surface of the rat cortex or hippocampus. The authors also validate NeuroGrid across species by showing that that it can capture LFP-modulated spiking activity intraoperatively in surgical patients, thus demonstrating its utility as tool for fundamental research on the human brain and in the clinic.

Autism spectrum disorders (ASDs) are characterized by both phenotypic and genetic heterogeneity. Here the authors find that ASD functional genetic networks are enriched for genes expressed in deep layer cortical neurons, that mutations in females impact more highly expressed genes as compared to males and that intellectual scores reflect the severity of mutations.

Anxiety symptoms may arise from an overgeneralization of negative memories to include more neutral ones. Here the authors show that the tuning of amygdala neurons for a conditioned stimulus broadens and matches the behavioral generalization to innocuous stimuli.

Wang and colleagues find that weakening hippocampal theta in a familiar environment reduces the performance of rats in a spatial memory task, decreases the number of theta sequences and degrades internally generated hippocampal episode cell firing, while leaving place cell firing intact. The same weakening of theta also prevents the formation of a precise spatial representation in a novel environment unless proximal cues are present. Together these results suggest that the mechanisms underlying internally generated hippocampal sequences of activity are crucial for episodic memory.

Here, the authors imaged calcium response in the mouse olfactory bulb in vivo to show that the calcium transients in astrocytic processes—but not cell bodies—are tightly coupled to neuronal activity and precede functional hyperemia.

Drosophila optic lobe neurons are generated from the outer and inner proliferation centers (IPC). The authors show a new mode of neurogenesis in which progenitors in one IPC domain migrate to a second domain where they mature into neural stem cells/neuroblasts. They also identify several genes that regulate this process.

Brain transcriptomics is limited by existing annotations of expressed gene products. Here the authors identify differentially expressed regions of the genome across development and aging in the human brain. These transcripts were developmentally conserved across the human and mouse and enriched for genetic variants associated with neurodevelopmental disorders.

The authors show that mice lacking the gene Erbb4 in somatostatin-expressing (SOM) neurons of the thalamic reticular nucleus (TRN) show selective behavioral deficits in tasks involving switching attention between cues of different sensory modalities. Slice recordings also showed enhanced cortical drive in Erbb4-deficient TRN SOM neurons.

The inhibitory neurotransmitter GABA can lead to neuronal depolarization during early brain development caused by a shift in intracellular chloride concentration. Here Deidda et al. show that a brief alteration in depolarizing GABA during early development can modulate critical-period plasticity in the visual cortex later in development, and this effect is mediated by perinatal BDNF signaling.

Combining patch-clamp recordings and subsequent STORM imaging of individual cells, the authors show that the axon terminals of perisomatically- and dendritically-projecting GABAergic interneurons show differences in CB₁ receptor number, active zone complexity, and receptor:effector ratio. Chronic exposure to THC evoked a dose-dependent and long-lasting downregulation of CB₁ at these synapses.

Light increments and decrements are encoded in the retina by ON and OFF ganglion cells. The polarity of these cells' responses is thought to be fixed, but Tikidji-Hamburyan and colleagues now demonstrate in mouse and pig retina that they can change depending on ambient illuminance. For instance, an OFF cell can gain or lose an ON response at different light levels. Such changes in response polarity propagate to higher visual centers in vivo.

Here the authors find that PlexinA1, a well-known Semaphorin receptor, is also a receptor for Slits. Utilizing phenotypic analysis of mouse models, they define an in vivo contribution of Plexin-Slit signaling during commissural axon guidance and demonstrate the role of the Slit C-terminal fragment in this process.

Sensory stimuli fluctuate on many timescales but short-term plasticity causes synapses to act as temporal filters, limiting the range of frequencies they can transmit. Here, the authors show how the interaction of multiple synaptic and circuit mechanisms can reduce synaptic depression to promote faithful coding of both fast and slow stimuli.

The authors used human embryonic stem cells or induced pluripotent stem cells to derive sensory neurons that have biochemical and electrophysiological properties similar to touch receptors, including the ability to transduce mechanical stimuli into electrical activity. Using CRISPR/Cas9 gene targeting technology, they also show that the mechanosensitivity of these cells relies entirely on the expression of PIEZO2.

By recording neural activity in the lateral amygdala in awake and behaving rats, Ghosh and Chattarji show that neural encoding of fear generalization involves reduction of specific response to fear-associated cues at the single-neuron level. The study also shows that increasing neuronal excitability in the lateral amygdala can promote fear generalization and that the auditory cortex is not involved when fear-inducing conditioning stimulus is based on sound.