Global change in brain state during spontaneous and forced walk in is composed of combined activity patterns of different neuron classes.

Movement-correlated brain activity has been found across species and brain regions. Here, we used fast whole brain lightfield imaging in adult to investigate the relationship between walk and brain-wide neuronal activity. We observed a global change in activity that tightly correlated with spontaneous bouts of walk.

Acoustic communication: Deer mice join the chorus.

A new study has identified two distinct pup vocalizations in deer mice, showing that discrete genetic loci explain the acoustic variation between these two call types and that the calls elicit different levels of maternal responsiveness.

A lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins.

Acute lysosomal membrane damage reduces the cellular population of functional lysosomes. However, these damaged lysosomes have a remarkable recovery potential independent of lysosomal biogenesis and remain unaffected in cells depleted in TFEB and TFE3. We combined proximity-labelling-based proteomics, biochemistry and high-resolution microscopy to unravel a lysosomal membrane regeneration pathway that depends on ATG8, the lysosomal membrane protein LIMP2, the RAB7 GTPase-activating protein TBC1D15 and proteins required for autophagic lysosomal reformation, including dynamin-2, kinesin-5B and clathrin.

BDNF signaling in correlation-dependent structural plasticity in the developing visual system.

During development, patterned neural activity instructs topographic map refinement. Axons with similar patterns of neural activity converge onto target neurons and stabilize their synapses with these postsynaptic partners, restricting exploratory branch elaboration (Hebbian structural plasticity). On the other hand, non-correlated firing in inputs leads to synapse weakening and increased exploratory growth of axons (Stentian structural plasticity).

Interhemispheric competition during sleep.

Our understanding of the functions and mechanisms of sleep remains incomplete, reflecting their increasingly evident complexity. Likewise, studies of interhemispheric coordination during sleep are often hard to connect precisely to known sleep circuits and mechanisms. Here, by recording from the claustra of sleeping bearded dragons (Pogona vitticeps), we show that, although the onsets and offsets of Pogona rapid-eye-movement (REM) and slow-wave sleep are coordinated bilaterally, these two sleep states differ markedly in their inter-claustral coordination.

A multi-omics view of neuronal subcellular protein synthesis.

While it has long been known that protein synthesis is necessary for long-term memory in the brain, the logistics of neuronal protein synthesis is complicated by the extensive subcellular compartmentalization of the neuron. Local protein synthesis solves many of the logistic problems posed by the extreme complexity of dendritic and axonal arbors and the huge number of synapses. Here we review recent multi-omic and quantitative studies that elaborate a systems view of decentralized neuronal protein synthesis.

Interconnected sub-networks of the macaque monkey gustatory connectome.

Macroscopic taste processing connectivity was investigated using functional magnetic resonance imaging during the presentation of sour, salty, and sweet tastants in anesthetized macaque monkeys. This examination of taste processing affords the opportunity to study the interactions between sensory regions, central integrators, and effector areas. Here, 58 brain regions associated with gustatory processing in primates were aggregated, collectively forming the .

Genetic manipulation and targeted protein degradation in mammalian systems: practical considerations, tips and tricks for discovery research.

Gaining a mechanistic understanding of the molecular pathways underpinning cellular and organismal physiology invariably relies on the perturbation of an experimental system to infer causality. This can be achieved either by genetic manipulation or by pharmacological treatment. Generally, the former approach is applicable to a wider range of targets, is more precise, and can address more nuanced functional aspects.

Insights into the sulfur metabolism of Chlorobaculum tepidum by label-free quantitative proteomics.

Chlorobaculum tepidum is an anaerobic green sulfur bacterium which oxidizes sulfide, elemental sulfur, and thiosulfate for photosynthetic growth. It can also oxidize sulfide to produce extracellular S globules, which can be further oxidized to sulfate and used as an electron donor. Here, we performed label-free quantitative proteomics on total cell lysates prepared from different metabolic states, including a sulfur production state (10 h post-incubation [PI]), the beginning of sulfur consumption (20 h PI), and the end of sulfur consumption (40 h PI), respectively.

Rhodamine-Sensitized Two-Photon Activation of a Red Light-Absorbing BODIPY Photocage.

Two-photon (2P) activatable probes are of high value in biological and medical chemistry since near infrared (NIR) light can penetrate deeply even in blood-perfused tissue and due to the intrinsic three-dimensional activation properties. Designing two-photon chromophores is challenging. However, the two-photon absorption qualities of a photocage can be improved with an intramolecular sensitizer, which transfers the absorbed light onto the cage.

Essential protein P116 extracts cholesterol and other indispensable lipids for Mycoplasmas.

Mycoplasma pneumoniae, responsible for approximately 30% of community-acquired human pneumonia, needs to extract lipids from the host environment for survival and proliferation. Here, we report a comprehensive structural and functional analysis of the previously uncharacterized protein P116 (MPN_213). Single-particle cryo-electron microscopy of P116 reveals a homodimer presenting a previously unseen fold, forming a huge hydrophobic cavity, which is fully accessible to solvent.

Single spikes drive sequential propagation and routing of activity in a cortical network.

Single spikes can trigger repeatable firing sequences in cortical networks. The mechanisms that support reliable propagation of activity from such small events and their functional consequences remain unclear. By constraining a recurrent network model with experimental statistics from turtle cortex, we generate reliable and temporally precise sequences from single spike triggers.

Complementary and alternative medicine use in narcolepsy.

Background: Management of narcolepsy includes behavior strategies and symptomatic pharmacological treatment. In the general population, complementary and alternative medicine (CAM) use is common in Europe (30%), also in chronic neurological disorders (10-20%). The aim of our study was to evaluate frequency and characteristics of CAM use in German narcolepsy patients.

De-centralizing the Central Dogma: mRNA translation in space and time.

As our understanding of the cell interior has grown, we have come to appreciate that most cellular operations are localized, that is, they occur at discrete and identifiable locations or domains. These cellular domains contain enzymes, machines, and other components necessary to carry out and regulate these localized operations. Here, we review these features of one such operation: the localization and translation of mRNAs within subcellular compartments observed across cell types and organisms.

Inhibitory top-down projections from zona incerta mediate neocortical memory.

Top-down projections convey a family of signals encoding previous experiences and current aims to the sensory neocortex, where they converge with external bottom-up information to enable perception and memory. Whereas top-down control has been attributed to excitatory pathways, the existence, connectivity, and information content of inhibitory top-down projections remain elusive. Here, we combine synaptic two-photon calcium imaging, circuit mapping, cortex-dependent learning, and chemogenetics in mice to identify GABAergic afferents from the subthalamic zona incerta as a major source of top-down input to the neocortex.

Unbiased choice of global clustering parameters for single-molecule localization microscopy.

Single-molecule localization microscopy resolves objects below the diffraction limit of light via sparse, stochastic detection of target molecules. Single molecules appear as clustered detection events after image reconstruction. However, identification of clusters of localizations is often complicated by the spatial proximity of target molecules and by background noise.

Isolation of a novel heterodimeric PSII complex via strep-tagged PsbO.

The multi-subunit membrane protein complex photosystem II (PSII) catalyzes the light-driven oxidation of water and with this the initial step of photosynthetic electron transport in plants, algae, and cyanobacteria. Its biogenesis is coordinated by a network of auxiliary proteins that facilitate the stepwise assembly of individual subunits and cofactors, forming various intermediate complexes until fully functional mature PSII is present at the end of the process. In the current study, we purified PSII complexes from a mutant line of the thermophilic cyanobacterium Thermosynechococcus vestitus BP-1 in which the extrinsic subunit PsbO, characteristic for active PSII, was fused with an N-terminal Twin-Strep-tag.

Protocol for making an animal model of "blindsight" in macaque monkeys.

Patients with damage to the primary visual cortex (V1) can respond correctly to visual stimuli in their lesion-affected visual field above the chance level, an ability named blindsight. Here, we present a protocol for making an animal model of blindsight in macaque monkeys. We describe the steps to perform pre-lesion training of monkeys on a visual task, followed by lesion surgery, post-lesion training, and evaluation of blindsight.

Nonlinear EEG signatures of mind wandering during breath focus meditation.

In meditation practices that involve focused attention to a specific object, novice practitioners often experience moments of distraction (i.e., mind wandering).

Stability and learning in excitatory synapses by nonlinear inhibitory plasticity.

Synaptic changes are hypothesized to underlie learning and memory formation in the brain. But Hebbian synaptic plasticity of excitatory synapses on its own is unstable, leading to either unlimited growth of synaptic strengths or silencing of neuronal activity without additional homeostatic mechanisms. To control excitatory synaptic strengths, we propose a novel form of synaptic plasticity at inhibitory synapses.

Adaptation of larva foraging in response to changes in food resources.

All animals face the challenge of finding nutritious resources in a changing environment. To maximize lifetime fitness, the exploratory behavior has to be flexible, but which behavioral elements adapt and what triggers those changes remain elusive. Using experiments and modeling, we characterized extensively how larvae foraging adapts to different food quality and distribution and how the foraging genetic background influences this adaptation.

Probing top-down information in neocortical layer 1.

Accurate perception of the environment is a constructive process that requires integration of external bottom-up sensory signals with internally generated top-down information. Decades of work have elucidated how sensory neocortex processes physical stimulus features. By contrast, examining how top-down information is encoded and integrated with bottom-up signals has been challenging using traditional neuroscience methods.

Conformational changes in mitochondrial complex I of the thermophilic eukaryote .

Mitochondrial complex I is a redox-driven proton pump that generates proton-motive force across the inner mitochondrial membrane, powering oxidative phosphorylation and ATP synthesis in eukaryotes. We report the structure of complex I from the thermophilic fungus , determined by cryoEM up to 2.4-Å resolution.

Regulation of circuit organization and function through inhibitory synaptic plasticity.

Diverse inhibitory neurons in the mammalian brain shape circuit connectivity and dynamics through mechanisms of synaptic plasticity. Inhibitory plasticity can establish excitation/inhibition (E/I) balance, control neuronal firing, and affect local calcium concentration, hence regulating neuronal activity at the network, single neuron, and dendritic level. Computational models can synthesize multiple experimental results and provide insight into how inhibitory plasticity controls circuit dynamics and sculpts connectivity by identifying phenomenological learning rules amenable to mathematical analysis.

Logistics of neuronal protein turnover: Numbers and mechanisms.

Research in the past twenty years or so has revealed that neurons synthesize and degrade proteins at their synapses to enable synaptic proteome remodelling on demand and in real-time. Here we provide a quantitative overview of the decentralized neuronal protein-turnover logistics. We first analyse the huge neuronal protein turnover demand that arises from subcellular compartments outside the cell body, followed by an overview of key quantities and modulation strategies in neuronal protein turnover logistics.