Updated May 26, 2020
Research Spotlight
Most people associate stroke with the elderly, but the incidence of stroke in newborns is similar to that in the elderly and leads to severe long-term neurological outcomes. Circulating immune cells and immune cells in the brain play important roles in determining how stroke injury progresses in both newborns and adults; yet, the relative contribution of these cells critically depends on brain maturation at the time of stroke. Here, in a mouse model of neonatal stroke, Rayasam et al. show that the choroid plexus (CP), a dynamic structure that controls trafficking of immune cells and nutrients between blood, CSF and brain, modulates injury by several types of immune cells that accumulate in the CP and signal to post-ischemic brain. Improved understanding of the leukocyte populations accumulated in the CP can yield novel therapeutic avenues for treating neonatal stroke.
The sensory environment around us is continuously changing. In such a probabilistic environment, our brain can infer the causes of the sensory input and continuously update expectations based on past experiences. How the prior belief of sensory events inferred from past experiences affects brain connectivity for updating future expectations remains unexplored. Combining computational modelling and fMRI, Wang et al. showed that during tactile associative learning, prior beliefs differentially modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex) depending on whether the targets were expected or unexpected. The modulatory strength of prior belief on these insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These findings suggest that the insular cortex acts as a gate to control belief updating and, hence, to guide future decision-making during probabilistic tactile learning.
Brain-Wide Mapping of Water Flow Perception in Zebrafish
Humans mainly rely on their vision and sound to navigate their surroundings, but fish have an additional sense that humans lack: they can sense the flow of water around them, complemented by their vision. Until now, our understanding of how their brains interpret water flow has been rudimentary. Using cutting edge microscopy and a novel microfluidics device, Vanwalleghem et al. captured images of larval zebrafish brain activity whilst the fish experienced water flow in their surroundings. By tracking thousands of neurons and their activity through time, the authors were able to identify the ways in which neurons respond when water flow events happen, and the functional networks they may form across the brain. This study provides a first tantalizing glimpse of the flow-sensing brain-wide network and a departure point for targeted studies of its structural and mechanistic detail.
There is increasing interest to create genetically-manipulated monkey models that bear some behavioral resemblance to neuropsychiatric conditions in humans, although the underlying circuit mechanisms remain largely unexplored and whether they are shared by human patients remains unknown. Using a group of macaque monkeys carrying extra copies of MECP2 gene, Cai et al. conducted a combination of genetic, behavioral, neurophysiological and neuroimaging investigations and found that MECP2 co-expressed genes are enriched in GABA-related signal pathways. The authors have identified that reduced beta synchronization within fronto-parieto-occipital networks was associated with elevated circular routing, while functional hyper-connectivity in prefrontal and cingulate networks was related to regressive deficits in reversal learning tasks in transgenic monkeys. Interestingly, circuit abnormalities in monkeys highly correspond to those in a stratified subgroup of autistic patients. This study not only uncovers pathophysiological circuits of transgenic monkeys, but also provides a new means to dissect the heterogeneity of patients with autism spectrum disorder.
Most-Discussed Research Published in April
Below are five Early Release articles that generated the most online discussion in April 2020, as measured by Altmetric. Altmetric data is available for all articles published in JNeurosci on the Info & Metrics tab. Learn more about how the Altmetric score is calculated.
There is little understanding about the molecular mechanisms involved in the development of depression and in severe cases, suicide. Evidence for the role of microtubule modifications in progression of depressive disorders is emerging. These postmortem data provide strong evidence for membrane tubulin modification leading to reduced efficacy of the G protein, Gsα, in depression. This study reveals a direct link between decreased tubulin acetylation in human depression and the increased localization of Gαs in lipid-raft domains responsible for attenuated cAMP signaling. The evidence presented here suggest a novel diagnostic and therapeutic locus for depression.
In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience and attention related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.
A Causal Role for Mouse Superior Colliculus in Visual Perceptual Decision-Making
The mouse superior colliculus has become a popular model for studying the circuit organization and development of the visual system. Although the SC is a fundamental component of the visual pathways in mice, its role in visual perceptual decision-making is not clear. By investigating how temporally precise SC inhibition influenced behavioral performance during a visually guided orientation change detection task, we identified a 100-ms temporal epoch of SC visual activity that is crucial for the ability of mice to detect behaviorally relevant visual changes. In addition, we found that SC inhibition also caused deficits in visual target selection. Thus, our findings highlight the importance of the SC for visual perceptual choice behavior in the mouse.
Whether STN local cells contribute to the therapeutic effects of STN DBS in PD remains unclear. We re-examined the role of STN local cells in mediating the symptom-relieving effects of STN DBS using cell type specific optogenetic stimulation with a much faster opsin, Chronos. Direct optogenetic stimulation of STN neurons was effective in treating the symptoms of parkinsonism in the 6-OHDA lesion rat. These results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation/inhibition and must be considered when employing optogenetic to study high rate neural stimulation.
Synaptic mechanisms of general anesthesia remain unidentified. In rat brainstem slices, isoflurane inhibits excitatory transmitter release by blocking presynaptic Ca2+ channels and exocytic machinery, with the latter mechanism predominating in its inhibitory effect on high-frequency transmission. Both in slice and in vivo, isoflurane preferentially inhibits spike transmission induced by high-frequency presynaptic inputs. This low-pass filtering action of isoflurane likely plays a significant role in general anesthesia.
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