Controlling the behaviour of Drosophila melanogaster via smartphone optogenetics.

Invertebrates such as Drosophila melanogaster have proven to be a valuable model organism for studies of the nervous system. In order to control neuronal activity, optogenetics has evolved as a powerful technique enabling non-invasive stimulation using light. This requires light sources that can deliver patterns of light with high temporal and spatial precision.

Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination.

Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al.

Synaptic vesicles transiently dock to refill release sites.

Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must 'dock' to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation, then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone.

Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep-wake states.

Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5'-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal.

Undisturbed climbing fiber pruning in the cerebellar cortex of CX CR1-deficient mice.

Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)-to-Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning-relevant processes during early postnatal development. Until now, the role of microglia in pruning remains under intense investigation.

Extinction of cue-evoked food-seeking recruits a GABAergic interneuron ensemble in the dorsal medial prefrontal cortex of mice.

Animals must quickly adapt food-seeking strategies to locate nutrient sources in dynamically changing environments. Learned associations between food and environmental cues that predict its availability promote food-seeking behaviors. However, when such cues cease to predict food availability, animals undergo "extinction" learning, resulting in the inhibition of food-seeking responses.

The role of spreading depolarizations and electrographic seizures in early injury progression of the rat photothrombosis stroke model.

Spreading depolarization (SD) and seizures are pathophysiological events associated with cerebral ischemia. Here, we investigated their role for injury progression in the cerebral cortex. Cerebral ischemia was induced in anesthetized male Wistar rats using the photothrombosis (PT) stroke model.

Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes.

Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3). We have characterized recently generated Piccolo KO ( ) rats.

Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84.

Background: Medium-chain fatty acids and their 3-hydroxy derivatives are metabolites endogenously produced in humans, food-derived or originating from bacteria. They activate G protein-coupled receptors, including GPR84 and HCA, which regulate metabolism and immune functions. Although both receptors are coupled to G proteins, share at least one agonist and show overlapping tissue expression, GPR84 exerts pro-inflammatory effects whereas HCA is involved in anti-inflammatory responses.

Gradients in the mammalian cerebellar cortex enable Fourier-like transformation and improve storing capacity.

Cerebellar granule cells (GCs) make up the majority of all neurons in the vertebrate brain, but heterogeneities among GCs and potential functional consequences are poorly understood. Here, we identified unexpected gradients in the biophysical properties of GCs in mice. GCs closer to the white matter (inner-zone GCs) had higher firing thresholds and could sustain firing with larger current inputs than GCs closer to the Purkinje cell layer (outer-zone GCs).

Developmental Increase of Neocortical Presynaptic Efficacy Maturation of Vesicle Replenishment.

The efficacy of neocortical synapses to transmit during bursts of action potentials (APs) increases during development but the underlying mechanisms are largely unclear. We investigated synaptic efficacy at synapses between layer 5 pyramidal neurons (L5PNs) during development, using paired recordings, presynaptic two-photon Ca imaging, and numerical simulations. Our data confirm a developmental increase in paired-pulse ratios (PPRs).

UNI-EM: An Environment for Deep Neural Network-Based Automated Segmentation of Neuronal Electron Microscopic Images.

Recently, there has been rapid expansion in the field of micro-connectomics, which targets the three-dimensional (3D) reconstruction of neuronal networks from stacks of two-dimensional (2D) electron microscopy (EM) images. The spatial scale of the 3D reconstruction increases rapidly owing to deep convolutional neural networks (CNNs) that enable automated image segmentation. Several research teams have developed their own software pipelines for CNN-based segmentation.

GABA-Glycine Cotransmitting Neurons in the Ventrolateral Medulla: Development and Functional Relevance for Breathing.

Inhibitory neurons crucially contribute to shaping the breathing rhythm in the brain stem. These neurons use GABA or glycine as neurotransmitter; or co-release GABA and glycine. However, the developmental relationship between GABAergic, glycinergic and cotransmitting neurons, and the functional relevance of cotransmitting neurons has remained enigmatic.

Heterogeneity of Astrocytes in Grey and White Matter.

Astrocytes are a diverse and heterogeneous type of glial cells. The major task of grey and white matter areas in the brain are computation of information at neuronal synapses and propagation of action potentials along axons, respectively, resulting in diverse demands for astrocytes. Adapting their function to the requirements in the local environment, astrocytes differ in morphology, gene expression, metabolism, and many other properties.

Large-Scale Mapping of Axonal Arbors Using High-Density Microelectrode Arrays.

Understanding the role of axons in neuronal information processing is a fundamental task in neuroscience. Over the last years, sophisticated patch-clamp investigations have provided unexpected and exciting data on axonal phenomena and functioning, but there is still a need for methods to investigate full axonal arbors at sufficient throughput. Here, we present a new method for the simultaneous mapping of the axonal arbors of a large number of individual neurons, which relies on their extracellular signals that have been recorded with high-density microelectrode arrays (HD-MEAs).

Loss of Orai2-Mediated Capacitative Ca Entry Is Neuroprotective in Acute Ischemic Stroke.

Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed.

Relation between activity-induced intracellular sodium transients and ATP dynamics in mouse hippocampal neurons.

Key Points: Employing quantitative Na -imaging and Förster resonance energy transfer-based imaging with ATeam1.03 (ATeam), we studied the relation between activity-induced Na influx and intracellular ATP in CA1 pyramidal neurons of the mouse hippocampus. Calibration of ATeam in situ enabled a quantitative estimate of changes in intracellular ATP concentrations.

HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons.

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC 40 µM; estimated endogenous cAMP concentration 13 µM).

Implications of the null mutation for synapsin phosphorylation, longevity, climbing proficiency and behavioural plasticity in adult .

The gene of encodes a highly abundant 47 kDa synaptic vesicle-associated protein. null mutants show defects in synaptic plasticity and larval olfactory associative learning but the molecular function of Sap47 at the synapse is unknown. We demonstrate that Sap47 modulates the phosphorylation of another highly abundant conserved presynaptic protein, synapsin.

Neocortical High Probability Release Sites Are Formed by Distinct Ca Channel-to-Release Sensor Topographies during Development.

Coupling distances between Ca channels and release sensors regulate vesicular release probability (p). Tight coupling is thought to provide a framework for high p and loose coupling for high plasticity at low p. At synapses investigated during development, coupling distances decrease, thereby increasing p and transmission fidelity.

Control of Presynaptic Parallel Fiber Efficacy by Activity-Dependent Regulation of the Number of Occupied Release Sites.

Parallel fiber (PF) synapses show pronounced and lasting facilitation during bursts of high-frequency activity. They typically connect to their target neurons a single active zone (AZ), harboring few release sites (~2-8) with moderate initial vesicular release probability (~0.2-0.

Enriched Environment Shortens the Duration of Action Potentials in Cerebellar Granule Cells.

Environmental enrichment for rodents is known to enhance motor performance. Structural and molecular changes have been reported to be coupled with an enriched environment, but functional alterations of single neurons remain elusive. Here, we compared mice raised under control conditions and an enriched environment.