Twister3: a simple and fast microwire twister.

OBJECTIVE: Twisted wire probes (TWPs, e.g. stereotrodes and tetrodes) provide a cheap and reliable method for obtaining high quality, multiple single-unit neural recordings in freely moving animals. Despite their ubiquity, TWPs are constructed using a tedious procedure consisting of manually folding, turning, and fusing microwire. This imposes a significant labor burden on research personnel who use TWPs in their experiments. APPROACH: To address this issue, we created Twister3, an open-source microwire twisting machine. This machine features a quick-draw wire feeder that eliminates manual wire folding, an auto-aligning motor attachment mechanism which results in consistently straight probes, and a high speed motor for rapid probe turning. MAIN RESULTS: Twister3 greatly increases the speed and repeatability of constructing twisted microwire probes compared to existing options. Users with less than one hour of experience using the device were able to make ~70 tetrodes per hour, on average. It is cheap, well documented, and all associated designs and source code are open-source. SIGNIFICANCE: Twister3 significantly reduces the labor burden of creating high-quality TWPs so electrophysiologists can spend more of their time performing recordings rather than making probes. Therefore, this device is of interest to any lab performing TWP neural recordings, for example, using microdrives.

Social Control of Hypothalamus-Mediated Male Aggression.

How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression.

Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors.

Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how Notch signaling regulates the quiescent, proliferative or differentiation behaviors of pancreatic progenitors at the single-cell level remains unclear. Here, using single-cell genetic analyses and a new transgenic system that allows dynamic assessment of Notch signaling, we address how discrete levels of Notch signaling regulate the behavior of endocrine progenitors in the zebrafish intrapancreatic duct. We find that these progenitors experience different levels of Notch signaling, which in turn regulate distinct cellular outcomes. High levels of Notch signaling induce quiescence, whereas lower levels promote progenitor amplification. The sustained downregulation of Notch signaling triggers a multistep process that includes cell cycle entry and progenitor amplification prior to endocrine differentiation. Importantly, progenitor amplification and differentiation can be uncoupled by modulating the duration and/or extent of Notch signaling downregulation, indicating that these processes are triggered by distinct levels of Notch signaling. These data show that different levels of Notch signaling drive distinct behaviors in a progenitor population.