Current Biology最新文献

Neurodegeneration often starts by atrophy of the cable-like nerve fibers (axons) that wire nervous systems. Maintaining axons requires supply via motor-protein-driven transport along uninterrupted bundles of microtubules. Functional loss of motor proteins, but surprisingly also their hyperactivation, links to conditions of axonal atrophy; in both cases the underlying mechanisms are little understood. To bridge this important knowledge gap, we carried out systematic studies using 40 different genetic tools to manipulate 19 context-related genes in one standardized Drosophila primary neuron system. Starting with transport motors, we found that downregulation in at least three of them-dynein heavy chain, the kinesin family member 5 (KIF5) ortholog kinesin heavy chain (Khc), and KIF1A ortholog Unc-104-caused disintegration of axonal microtubule bundles, which we refer to as "microtubule-curling"; this damages the essential highways for life-sustaining axonal transport. To understand this phenomenon, we focused on Khc's various subfunctions. We found that abolishing Khc-mediated mitochondrial and lysosomal transport affects the homeostasis of reactive oxygen species (ROS), which in turn triggers microtubule-curling in fly and mouse neurons alike. Taking the opposite approach by using conditions where Khc is hyperactive, we observed comparable microtubule-curling, triggered by an ROS-independent mechanism likely involving excessive mechanical force generation. To assess wider relevance of our findings, we studied Unc-104, its binding partner KIF-binding protein (KIFBP), and human KIF5A. These studies suggest that functional loss and hyperactivation of other transport motors also cause ROS-dependent and -independent microtubule-curling, which could therefore represent two fundamental pathways that link transport motors to microtubule bundle decay and neurodegeneration.

Path networks defined by patterns of intersections and orientations among individual paths may contain recurrent meta-structural features that can be learned and used in spatial reasoning and navigation.¹ Posterior parietal cortex (PPC) neurons exhibit scalable tuning to progress through routes,² suggesting that PPC in rats, as in humans, may function to encode common structure among multiple routes.^3,4,5,6 PPC neurons were recorded as rats performed a spatial working memory task within a network organized by recurrence in the layout of short and long pathways and right angle intersections. The specific routes utilized provided opportunity to contrast responses of PPC sub-populations to navigational actions with more complex responses that map route progress and features of route structure. We found evidence for the presence of PPC neurons that generalize in their firing patterns across routes having the same shape but opposite action series. A separate population discriminated the same routes and exhibited activity more closely related to angular velocity. The results indicate that PPC has the capacity to generalize the mapping of route progress and meta-structural organization in parallel with encoding of navigational actions. We suggest that such encoding can form the basis for learning the meta-structural organization of a non-random path network structure, such as that commonly found in cities. Further, the findings suggest that PPC could compute relationships between higher-order spatial information and navigational action sequences.

Translocation of an effector from one soil microbe into a competitor forces the recipient to swim away using a mechanism that bypasses canonical cyclic di-GMP repression of flagellar gene biosynthesis.

During transitions to a new leader male, gelada infants face a serious risk of infanticide. New research demonstrates that mothers reduce this risk by misrepresenting their fertility status.

Drosophila sLNv clock neurons release the co-packaged neuropeptides PDF and sNPF to regulate circadian behaviors and nighttime sleep.^1,2,3,4 Many studies of membrane potential and cytoplasmic Ca²⁺ at the sLNv soma emphasized elevations late at night or in the very early morning,^5,6,7,8,9 although action potential activity and synaptic release were not quantified. Recently, exocytosis of neuropeptide-containing dense-core vesicles (DCVs) at sLNv terminals was found to peak hours later at midmorning.¹⁰ To resolve the basis of the timing mismatch between somatic measurements and terminal exocytosis, recently developed probes were used to measure daily rhythms in sLNv neuron synaptic Ca²⁺ and sNPF release. Remarkably, at midmorning after soma Ca²⁺ has dropped, both Ca²⁺ spiking and clock-dependent native neuropeptide release peak in the distal terminals of the protocerebrum. Furthermore, Ca²⁺ in the soma and terminals differ in dependence on Ca²⁺ influx. Finally, synaptic DCV exocytosis requires Ca²⁺ spike activity at terminals that is not evident at the soma. These results lead to two striking conclusions. First, soma Ca²⁺ recording, which is the focus of many circuit studies, is not indicative of presynaptic Ca²⁺ and neuropeptide release in distal sLNv terminals. Second, daily clock- and activity-dependent sLNv terminal neuropeptide release occurs many hours in advance of known sLNv neuropeptide effects on nighttime sleep and morning behavior.

Soybean (Glycine max (L.) Merr.) is one of the most economically important crops in the world, but every year, pathogens cause billions of dollars' worth of losses worldwide. The domestication of this critical crop was associated with several severe genetic bottlenecks that resulted in a dramatic loss of genetic diversity (∼50%) relative to its wild progenitor. Although domestication selected for favorable agricultural traits, it is unclear how the reduced genetic diversity affected the immunity landscape of cultivated soybean relative to its wild ancestors. We performed a comprehensive screen for effector-triggered immune (ETI) responses of both cultivated soybean (Glycine max) and wild soybean (Glycine soja) against the bacterial speck pathogen Pseudomonas syringae. We uncovered an extensive ETI landscape in both species, with 121/529 alleles (22.9%) from 32/65 effector families (49.2%) eliciting ETI in G. max and 125/529 alleles (23.6%) from 23/65 effector families (35.4%) eliciting ETI in G. soja. Interestingly, soybean recognized all three effectors encoded in the conserved effector locus (CEL) of P. syringae (AvrE, HopM, and HopAA), providing pervasive and stacked resistance against this common soybean pathogen. Finally, we demonstrate that pretreatment of soybean with the CEL effectors can immunize soybean against subsequent infection. Overall, we have defined the ETI landscape of soybean against P. syringae and demonstrated that domestication has not compromised soybean immunodiversity despite a dramatic loss in genetic diversity.

To segregate chromosomes at cell division, the spindle must maintain its structure under force. How it does so remains poorly understood. To address this question, we use microneedle manipulation to apply local force to spindle microtubule bundles, kinetochore fibers (k-fibers), inside mammalian cells. We show that local load directly fractures k-fibers and that newly created plus-ends often have arrested dynamics, resisting depolymerization. Force alone, without fracture, is sufficient for spindle microtubule stabilization, as revealed by laser ablating k-fibers under local needle force. Doublecortin, which binds a compacted microtubule lattice, is lost around the force application site, suggesting local force-induced structural remodeling. In turn, end-binding protein 1 (EB1), which recognizes guanosine triphosphate (GTP)-tubulin, is locally enriched at stabilization sites, both before and after force-induced fracture. Together, our findings support a model in which force-induced damage leads to local spindle microtubule lattice remodeling and stabilization, which we propose reinforces the spindle where it experiences critical loads.

After the Permian-Triassic mass extinction, surviving lineages recovered in different ways. A new study reveals specific recovery trajectories in three different marine groups, some of which refilled lost morphological disparity while others exploited extinction-driven opportunities to innovate.

Humans and animals learn about the world through targeted and deliberate movement of the head, eyes, hands, and other sensors. A new study demonstrates how the geometry of the rat whisker system simplifies the motor control of active sensing.

Motivation often diminishes under aversive conditions. Clinically, motivational deficits are linked to psychiatric disorders such as depression and schizophrenia, yet the neural mechanisms by which aversive contexts suppress motivation remain unclear. Although classical theories associate motivation with the expected value of outcomes, less is known about the neural circuits that govern effort-based behavioral initiation. To address this, we dissociated motivational drive from goal valuation using an approach-avoidance (Ap-Av) task, in which macaques evaluated outcomes combining reward and punishment (air puffs to the face). As a control, we employed an approach-approach (Ap-Ap) task based solely on reward. Using chemogenetic manipulation, we found that selective inhibition of the ventral striatum to ventral pallidum (VS-VP) pathway restored the motivation to initiate trials in the Ap-Av task without affecting goal valuation. No effects were observed in the Ap-Ap task. These findings provide causal evidence that the VS-VP pathway mediates motivational suppression in aversive contexts. Electrophysiological recordings revealed rapid VS responses to aversive cues and a gradual decrease in VP activity, suggesting an inhibitory interaction in which elevated VS activity dampens VP output to limit initiation. The slower VP dynamics may reflect a process by which aversive signals are gradually integrated to influence the motivational state. Together, these results identify the VS-VP pathway as a key circuit by which aversive contexts suppress effort-based behavioral initiation, highlighting it as a potential target for treating motivational deficits in depression and schizophrenia.