Research articles

Chronic social defeat stress induces loss of protein claudin-5, leading to abnormalities in blood vessel morphology, increased blood brain barrier permeability, infiltration of immune signals and depression-like behaviors.

Quantitative mass spectrometry was used to produce a proteomic survey of postnatal human brain regions. Compared to matched RNA-seq, protein levels showed more regional variation, especially for membrane-associated proteins in the neocortex.

The relationship of resting-state hemodynamics signals to ongoing neural activity is poorly understood. Using optical imaging, electrophysiology, and local pharmacological infusions, Winder et al. found that resting hemodynamic signals were weakly correlated with neural activity and that these hemodynamic fluctuations persisted when neural activity was silenced.

Arid1b haploinsufficiency causes autism and intellectual disability, yet the neurobiological basis of this is unknown. The authors demonstrate that Arid1b-heterozygous mice have impaired cortical interneuron development and epigenetic signatures. These mice also have cognitive and social deficits, which are reversed by treatment with a GABA^A-receptor-positive allosteric modulator.

Cerebellar right Crus I (RCrusI) has been implicated in autism spectrum disorder (ASD). RCrusI modulation altered RCrusI–inferior parietal lobule connectivity, and this connectivity was atypical in children with ASD and in a TscI mouse model of ASD. Inhibition of RCrusI in mice led to autism-related behaviors, and RCrusI activation rescued social impairments in TscI mice.

The authors show that PKC-δ-expressing neurons in the central amygdala, are essential for synaptic plasticity underlying learning in the lateral amygdala, as they convey information about unconditioned stimulus to the lateral amygdala as a teaching signal.

Suzuki et al. found that food valuation is related to beliefs about nutritive attributes. Functional MRI revealed these attribute codes in lateral orbitofrontal cortex, suggesting a mechanism by which value signals are constructed from constituent attributes.

The critical period of ocular dominance (OD) plasticity in the visual cortex is initiated by maturation of inhibition. The authors show that thalamic relay neurons in mouse dorsolateral geniculate nucleus also undergo OD plasticity. This process depends on thalamic inhibition and is required for consolidating the OD shift in visual cortex.

Animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is poorly understood. The authors reveal a core function for TRPA1 in noxious heat transduction based on sensing H₂O₂ and ROS and demonstrate its conservation from planarians to humans.

Neurons in the lateral prefrontal cortex (but not the frontal eye fields) appear to maintain working memory information when disrupted by a transient distractor, not by using an immutable persistent code but by morphing from one persistent code to another. This code-morphing may provide the lateral prefrontal cortex with cognitive flexibility.

Davis et al. report that fear memories can be critically regulated by parvalbumin-expressing interneurons in the basolateral amygdala. Silencing these interneurons following fear memory extinction caused a reemergence of fear expression that was accompanied by increased activation of fear-encoding neurons and fear-associated 3–6 Hz oscillations within a basolateral amygdala–prefrontal cortex circuit.

The authors show how predictive representations are useful for maximizing future reward, particularly in spatial domains. They develop a predictive-map model of hippocampal place cells and entorhinal grid cells that captures a wide variety of effects from human and rodent literature.

The precise underpinnings of Parkinson's disease and other disorders associated with the accumulation of α-synuclein are unclear. This study shows that PrP^C mediates α-synuclein-associated synaptic dysfunction and memory deficits. Blocking specific events in receptor biology rescued cognitive deficits in mice, suggesting new possibilities for intervention in synucleinopathies.

The mechanisms of gliotransmitter release and their impact on neuronal signaling have remained largely elusive. The authors describe two functionally non-overlapping v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites. Thus, astrocytes are able to fine-tune fast glutamatergic neurotransmission and control fundamental processes of synaptic communication.

Astrocytes differentially regulate excitatory and inhibitory synaptic transmission in the CeM, the major output nucleus of the amygdala. Astrocytes thereby reduce neuronal activity in the CeM and diminish fear expression in vivo. Therefore, astrocytes influence neural network activity and animal behavior through the regulation of specific synapses.

Dopamine has long been thought to contribute to neurodegeneration in Parkinson's disease. The authors show that dopamine-induced neuron death in the substantia nigra is dependent on α-synuclein and coincides with increased levels of α-synuclein oligomers. The results suggest a synergistic interaction between dopamine and α-synuclein that underlies neuronal vulnerability in disease.

Spinal cord injury causes life-threatening infections. The authors report that this is partially mediated by a maladaptive neuroendocrine reflex, extending from the spinal cord to the adrenal glands, where it blocks catecholamines while producing immunosuppressive corticosteroids. The effect depends on the spinal injury level, and normalization of hormones production by the adrenals rescued mice from pneumonia.

The authors identify the midcingulate cortex as a region that gates nociceptive plasticity without modulating basal nociception or the affective component of acute pain in mice. They identify a novel pathway from the midcingulate cortex to the posterior insula that recruits descending serotonergic projections to facilitate nociception.

A small population of brainstem noradrenaline neurons powerfully modulates global brain function, but how they regulate diverse—and at times opposing—functions is not clear. The authors report that a modular organization in this neuromodulatory system, coupled with context-dependent activation modes, controls the balance between opposing emotional and flexible learning states.

Esr1⁺ cells in the VMHvl are well known to influence female sexual behaviors. Here the authors find a surprising new role of this population in female aggression. They further reveal that the female VMHvl contains two molecularly and anatomically distinct subdivisions: one for aggression and one for sex.