Research articles

Coupling distances between synaptic vesicles and Ca²⁺ channels determine the efficacy of neurotransmission. Böhme et al. find that presynaptic scaffold complexes spatiotemporally control Unc13 isoforms to establish two independent release pathways at subsynaptic active zones: Unc13B defines nascent, loosely coupled synapses whereas Unc13A facilitates release at mature synapses by tight coupling between Ca²⁺ channels and synaptic vesicles.

The authors find that the portion of rat somatosensory cortex representing the trident whiskers—a set of whiskers specialized for ground contact during exploration—encodes information about speed and acceleration of the animal. Microstimulation of this area alters running speed, consistent with the idea that trident whiskers and their neural representation could serve as a tactile speedometer.

Before children can read, their brains have yet to develop selective responses to words. This study demonstrates that a child's connectivity pattern at age 5 can predict where their own word-selective cortex will later develop. This suggests that connectivity lays the groundwork for later functional development of cortex.

In this study, the authors show that LTP lacks synapse specificity in hippocampi of aged (21–28 months) mice, possibly resulting from diminished levels of the K⁺/Cl⁻ cotransporter KCC2 and depolarizing GABA_A receptors. The KCC2 enhancer CLP257 restored synapse specificity of LTP, providing a possible new target for repairing memory loss in senescence.

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.

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.

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.

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.

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 analyzed the exome sequences of 2,104 intellectual disability patients and their parents. They identified 10 novel candidate genes associated with specific clinical phenotypes.

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.

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.

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.

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.

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.

Autism spectrum disorder is a complex disease with a strong genetic basis that remains under-characterized by current genetics studies. Here, the authors use a computational approach based on a human brain-specific gene network to predict autism-associated genes across the genome and further delineate their functional and developmental characteristics.

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.

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.

Using in vivo spinal cord two-photon calcium imaging, the authors provide the first comprehensive characterization of the representations of temperature in the spinal cord and reveal that spinal neurons encode temperature change for cold and absolute temperature for heat.