Volume 19 Issue 8, August 2016

Injured mouse retinal ganglion cells, upon a combination of treatments, can regrow their axons along the entire optic pathway and re-establish connections with their correct brain targets. This can partially restore function.

Orientation selectivity in visual cortex is not simply the result of linear input summation. Instead, selectivity is enhanced by nonlinear dendritic transformation of spatially clustered, cotuned synaptic inputs.

In the twenty-first century, microglia came of age. Their remarkable ontogeny, unique functions and gene expression profile, process motility, and disease relevance have all been highlighted. Neuroscientists interested in microglia encounter an obsolete concept, M1/M2 polarization, suggesting experimental strategies that produce neither conceptual nor technical advances. Ransohoff's Perspective argues against applying this flawed paradigm.

Prefrontal–hippocampal communication has been implicated in memory, but the temporal dynamics of information flow are not fully understood. In this study, the authors demonstrate that information flows between hippocampus and prefrontal cortex in different directions depending on the behavioral phase of a spatial-context-guided object discrimination task.

Safaiyan et al. demonstrate that myelin fragments progressively pinch off from aged myelin sheaths and are taken up and cleared by microglia. Age-associated myelin breakdown is substantial and saturates the degradative capacities of microglia, leading to lysosomal storage and an immune activation in microglia with time.

Feeding is controlled by hedonic cues that may override the homeostatic needs to eat, causing obesity. Labouèbe et al. have identified hypoglycemia-activated neurons in the paraventricular thalamus that increase motivated sucrose-seeking behavior. As their activity is not suppressed by fructose or sweeteners, these cells may contribute to sugar overconsumption and diabetes.

In this study, Wilson et al. find that dendritic spines on neurons in the visual cortex cluster according to orientation preference. The degree of clustering on single neurons strongly predicts somatic orientation selectivity and the prevalence of local dendritic signals in the dendritic field, suggesting a role for dendritic computation in shaping orientation selectivity.

Neurotransmission is regulated by glial cells; however, the underlying mechanisms are not fully understood. Sun and colleagues provide evidence that Lrp4 in astrocytes facilitates glutamatergic transmission by controlling ATP release. Their results provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.

The vesicular transporter VGAT controls GABA vesicle filling at inhibitory terminals. Here Meye et al. show that cocaine withdrawal reduces VGAT at synapses from pallidum to lateral habenula, thereby decreasing inhibitory transmission. This GABAergic synaptic plasticity is crucial for behaviors modeling cocaine-evoked aversive states and stress-induced relapse.

The authors show how dopamine neurons operate in the context of cholinergic transmission and find that the afferents originating from two functionally distinct (motor and limbic) cholinergic nuclei of the brainstem selectively modulate subsets of neurons in the ventral tegmental area.

The authors mapped thalamocortical connectivity in local networks of excitatory neurons in mouse visual cortex. They found that interconnected neurons in layer 4 and translaminar pairs of connected L4–L2/3 neurons receive common inputs from the thalamus.

Human intracranial amygdala recordings reveal fast-latency responses to broad and low, but not high, spatial frequency components of fearful, but not happy or neutral, faces, which are not observed with unpleasant scenes. Amygdala fearful face responses are faster than in fusiform cortex, supporting a phylogenetically old, subcortical pathway to human amygdala.

By studying a severe neuropathy in mice, Quintes, Brinkmann et al. demonstrate that the nuclear zinc-finger protein Zeb2 (Sip1) is essential for Schwann cell differentiation and myelin synthesis. Since Zeb2-deficient Schwann cells continuously express repressors of lineage progression, ‘inhibiting the inhibitors’ emerges as a new principle of peripheral myelination control.

This study shows that the transcriptional regulator Zeb2 is required for the onset of peripheral myelination and remyelination. Zeb2 recruits HDAC1–HDAC2–NuRD co-repressor complexes to antagonize inhibitory effectors including Notch, while activating promyelinogenic factors. A Mowat-Wilson syndrome–associated ZEB2 mutation disrupting HDAC–NuRD interaction abolishes Zeb2 activity for Schwann cell differentiation.

A combination of increased neural activity, induced by visual stimulation or using chemogenetics, and increasing mTOR signaling promotes retinal ganglion cell axon regeneration and partial recovery of visual behaviors after injury.

The authors show that tau can be released by neurons and transferred to other neurons via the extracellular space. Moreover, they show that enhancing neuronal activity accelerates transneuronal tau propagation and exacerbates tau pathology.

RNA sequences are generally considered to be a mirror of DNA sequences. However, that dogma has become challenged as RNA editing is increasingly recognized. This study explored the global landscape of RNA editing in human brain development and revealed its dynamic aspects, providing insight into epitranscriptional regulation of sequence diversity.

Hintiryan, Foster et al. present an online mouse cortico-striatal projectome describing projections from the entire cortex to dorsal striatum. Computational neuroanatomic analysis of these projections identified 29 distinct striatal domains. This connectomics approach was applied to characterize circuit-specific cortico-striatal connectopathies in a mouse model of Huntington disease and in monoamine oxidase (MAO) A/B knockout mice.