Articles in 2014

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.

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.

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.

Extraretinal signals such as efference copy are generally thought to be critical for discounting visual image motion caused by eye movements. However, theoretical work suggests that eye rotations could be estimated directly from optic flow. Here the authors show that MT neurons use such ‘dynamic perspective’ cues to disambiguate depth.

M. Aghajan and colleagues recorded hippocampal activity in rats foraging in a two-dimensional virtual reality (VR) environment. Spatial selectivity was absent but phase precession was intact, occurring within 2-s-long hippocampal motifs. Selectivity to space and distance traveled were greatly enhanced when the rats repeatedly followed systematic paths. The results demonstrate that distal visual cues alone are insufficient to generate a robust hippocampal rate code for space but are sufficient to generate a temporal code.

In this study, the authors show that they can induce the direct conversion of fibroblasts into nociceptor neurons via the expression of only five key transcription factors. They further confirm that these induced neurons are bona fide nociceptors by demonstrating that their expression profiles resemble that of their endogenous counterparts and show that they are responsive to common nociceptor agonists.

In this study, the authors show that monkeys can learn to use non-biomimetic proprioceptive feedback, delivered via electrical microstimulation of somatosensory cortex, to guide motor movements. The monkeys also integrated this artificial feedback with vision to optimize motor performance. The results suggest new learning-based approaches both to providing sensory feedback for brain–machine interfaces and to studying the neural mechanisms of adaptive sensory integration.

In this study, the authors show that expression of Brn3a with Ngn1 or 2 can induce the direct reprogramming of mouse and human fibroblasts into peripheral sensory neurons. They further demonstrate that these neurons exhibit the expression profiles and physiological properties of mature sensory neurons and are responsive to nociceptor agonists.

Earlier work suggests that spatial phase preferences are randomly distributed throughout visual cortex. In this study, the authors present evidence towards a columnar organization for spatial phase that resembles organization for orientation preference, which suggests that this phase organization may contribute to the emergence of orientation maps.

The authors show that mice lacking Fragile X Mental Retardation Protein (FMRP) have disrupted neuronal migration during cortical development. FMRP-deficient mice also show altered excitatory-to-inhibitory balance early postnatally. They identify N-cadherin as a target of FMRP and show that re-expressing N-cadherin can rescue these phenotypes in FMRP-deficient mice.

The authors report that in mice, the cerebellum modulates the activity of the striatum via a disynaptic pathway to facilitate optimal motor control. Dysfunction of this pathway can contribute to dystonia.