Research articles

Unexpected rewards activate midbrain dopamine neurons, and this response is proposed to support learning by signaling discrepancies between actual and expected outcomes. Here the authors use optogenetic stimulation to demonstrate a causal role for temporally precise dopamine neuron signaling in cue-reward learning.

Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology.

The authors examined neuronal responses in V1 and V2 to synthetic texture stimuli that replicate higher-order statistical dependencies found in natural images. V2, but not V1, responded differentially to these textures, in both macaque (single neurons) and human (fMRI). Human detection of naturalistic structure in the same images was predicted by V2 responses, suggesting a role for V2 in representing natural image structure.

In this study, the authors use selective silencing of specific subsets of afferent neurons and stimulation with pruritogens or algogens to show that histaminergic and non-histaminergic itch is mediated by functionally distinct sets of sensory fibers. These findings provide further evidence for the labeled line theory of sensory perception.

Imaging calcium and vesicular release from thousands of synapses during contrast adaptation, Nikolaev and colleagues reveal the stratified organization of depressing and facilitating bipolar cells terminals in the zebrafish retina. The study also offers some insights into the cellular and circuit mechanisms of bidirectional gain modulation in this sensory system.

Odors evoke complex spatiotemporal patterns of activity in the olfactory bulb. The authors show that the spike rates of downstream piriform cortex neurons (PCNs) reflect the relative timing of activation. Posterior PCNs are more sensitive to input timing than anterior PCNs.

The authors identify a hemispheric asymmetry in neurogenesis in adult zebrafish. This asymmetry could be reversed by olfactory sensory deprivation or decreasing Notch signaling on the left side. Behavioral responses of fish to olfactory cues depended on the left olfactory epithelium, which may be a result of this asymmetry in neurogenesis.

Prior anatomical studies have suggested that intratelencephalic (IT) and pyramidal tract (PT) cortical neurons project to different populations of striatal spiny projection neurons (SPNs). Here, the authors find using optogenetic stimulation that both IT and PT neurons project to both direct and indirect pathway SPNs.

Here the authors report evidence for the neural correlates of confidence in the primate pulvinar, a visual thalamic nucleus. Data from electrophysiological recordings, functional silencing and theoretical modeling indicate that pulvinar activity encodes a subject's certainty of visual categorization and contributes to perceptual confidence, which potentially underlies visual awareness.

In this study, the authors show that Dscam, a gene that has been implicated in Down syndrome, is targeted by the translation suppressor and Fragile X–linked protein FMRP. Loss of FMRP or overexpression of Dscam in Drosophila led to synaptic targeting errors and an impairment in perception of mechanical stimuli.

Making informed decisions requires taking into account how reliably choices produce expected outcomes. This study shows that primate anterodorsal septal neurons encode an uncertainty signal sensitive to reward size but do not carry information about the uncertainty of punishments.

Early-life stress, acting through corticotrophin-releasing hormone (CRH) and its receptor CRHR1, can have long-lasting effects on animals' behavior. Nectin-3 is a cell adhesion molecule whose heterodimeric interaction with presynaptic nectin-1 organizes the postsynaptic afadin–actin–N-cadherin complex to shape synaptic structure and function. Here, the authors show that structural synaptic adaptation and cognitive dysfunction in adulthood following early-life stress are dependent on CRH signaling acting through Nectin-3.

In this study, the authors show that MGE-derived interneuron progenitors, when engrafted into the adult hippocampus, can migrate long distances and functionally integrate into the host tissue. In addition, if these cells are engrafted into the brain after the initiation of epilepsy, seizure frequency and behavioral deficits are reduced.

Temporal and spatial integration of synaptic inputs onto dendrites can display linear, sublinear and supralinear motifs in vitro. A study now examines this issue in vivo in mouse binocular visual cortex. It shows that dendritic integration of binocular information is sublinear, leading to a divisive form of gain control that linearizes the output of binocular neurons and enhances orientation selectivity.

Long-term exposure to glucocorticoids following chronic stress is detrimental to cognitive processes including learning and memory. Even so, short term glucocorticoid surges can facilitate cognition. Here the authors show that the circadian oscillation in circulating glucocorticoids is important for motor skill learning–induced dendritic spine remodeling. They also show that circadian glucocorticoid-mediated synaptic modification acts through non-transcriptional mechanism involving cytoskeleton remodeling and correlates with long-term memory retention.

In this study, the authors identify the ER-localized protein Meigo as a modulator of dendritic and axonal targeting of olfactory neurons. They find that Meigo is essential for maintaining protein levels and N-glycosylation of Ephrin in the ER, thereby regulating its function in axonal and dendritic refinement.

In response to the movement of its visual world, Drosophila is capable of optomotor response in head and body turning, as well as a visual fixation response. This study shows that blocking the visual pathway activity responsible for optokinetic response in flies does not affect the visual fixation response, suggesting two distinct pathways for processing each set of information. By doing so, the authors also devised a neural and behavioral hierarchy in fly visual system where fixation behavior and the neurons mediating fixation response are upstream of optokinetic response as performed by lobula plate neurons.

In this study, the authors use time-lapse in vivo two-photon imaging to elucidate the dynamics of NG2⁺ gial cells in the cortex. They find that proliferation and migration of these cells is intimately linked to the loss of neighboring cells to cell death or differentiation.

Prevailing models have suggested that grid cell firing in the entorhinal cortex for spatial navigation relies on theta rhythmic inputs from head direction cells. Here, the authors show how head direction cells can skip theta cycles in a regular and organized manner in which two head direction cells will alternate theta skipping in opposing cycles. This so-called theta skipping is dependent on the input from the septum, and these results propose a possible mechanism of spatial computation.

In primary visual cortex (V1), adaptation controls the responsiveness of individual neurons and shifts their visual selectivity. Here the authors examine adaptation at the population level. They conclude that adaptation in V1 acts as a mechanism of homeostasis, enforcing a tendency towards equality and independence in neural activity across the population.