Ultrasonic Songs of Male Mice

Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30–110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure. This study provides a quantitative initial description of male mouse songs, and opens the possibility of studying song production and perception in an established genetic model organism

Aberrations and their correction in light-sheet microscopy: A low-dimensional parametrization

Light sheet microscopy allows rapid imaging of three-dimensional fluorescent samples, using illumination and detection axes that are orthogonal. For imaging large samples, this often forces the objective to be tilted relative to the sample’s surface; for samples that are not precisely matched to the immersion medium index, this tilt introduces aberrations. Here we calculate the nature of these aberrations for a simple tissue model, and show that a low-dimensional parametrization of these aberrations facilitates online correction via a deformable mirror without introduction of beads or other fiducial markers. We use this approach to demonstrate improved image quality in living tissue

Image-based calibration of a deformable mirror in wide-field microscopy

Optical aberrations limit resolution in biological tissues, and their influence is particularly large for promising techniques like light-sheet microscopy. In principle, image quality might be improved by adaptive optics (AO), in which aberrations are corrected using a deformable mirror (DM). To implement AO in microscopy, one requires a method to measure wavefront aberrations, but the most commonly used methods have limitations for samples lacking point-source emitters. Here we implement an image-based wavefront-sensing technique, a variant of generalized phase-diverse imaging called multi-frame blind deconvolution, and exploit it to calibrate a DM in a light-sheet microscope. We describe two methods of parameterizing the influence of the DM on aberrations: a traditional Zernike expansion requiring 1,040 parameters, and a direct physical model of the DM requiring just 8 or 110 parameters. By randomizing voltages on all actuators, we show that the Zernike expansion successfully predicts wavefronts to an accuracy of approximately 30 nm (rms) even for large aberrations. We thus show that image-based wavefront sensing, which requires no additional optical equipment, allows for a simple but powerful method to calibrate a deformable optical element in a microscope setting

Organization of Vomeronasal Sensory Coding Revealed by Fast Volumetric Calcium Imaging

A long-standing goal in neuroscience is to perform exhaustive recording of each neuron in a functional local circuit. To achieve this goal, one promising approach is optical imaging of fluorescent calcium indicators, but typically the tens or hundreds of cells imaged simultaneously comprise only a tiny percentage of the neurons in an intact circuit. Here, we show that a recent innovation, objective-coupled planar illumination (OCPI) microscopy, permits simultaneous recording from three-dimensional volumes containing many thousand neurons. We used OCPI microscopy to record chemosensory responses in the mouse vomeronasal epithelium, for which expression of hundreds of receptor types implies high functional diversity. The implications of this diversity for sensory coding were examined using several classes of previously reported vomeronasal ligands, including sulfated steroids. A collection of just 12 sulfated steroids activated more than a quarter of the neurons in the apical vomeronasal epithelium; unexpectedly, responses were functionally organized into a modest number of classes with characteristic spatial distribution. Recording from a whole sensory system thus revealed new organizational principles

Knockout of lysosomal enzyme-targeting gene causes abnormalities in mouse pup isolation calls

Humans lacking a working copy of the GNPTAB gene suffer from the metabolic disease Mucolipidosis type II (MLII). MLII symptoms include mental retardation, skeletal deformities and cartilage defects as well as a speech delay with most subjects unable to utter single words (Otomo et al., 2009; Cathey et al., 2010; Leroy et al., 2012). Here we asked whether mice lacking a copy of Gnptab gene exhibited vocal abnormities. We recorded ultrasonic vocalizations from 5 to 8 day old mice separated from their mother and littermates. Although Gnptab(−/−) pups emitted a similar number of calls, several features of the calls were different from their wild type littermates. Gnptab(−/−) mice showed a decrease in the length of calls, an increase in the intra-bout pause duration, significantly fewer pitch jumps with smaller mean size, and an increase in the number of isolated calls. In addition, Gnptab(−/−) mice vocalizations had less power, particularly in the higher frequencies. Gnptab(+/−) mouse vocalizations did not appear to be affected. We then attempted to classify these recordings using these features to determine the genotype of the animal. We were able to correctly identify 87% of the recordings as either Gnptab(−/−) or Gnptab(+/+) pup, significantly better than chance, demonstrating that genotype is a strong predictor of vocalization phenotype. These data show that deletion of genes in the lysosomal enzyme targeting pathway affect mouse pup isolation calls

Circadian pacemaker neurons display cophasic rhythms in basal calcium level and in fast calcium fluctuations

SignificanceDaily rhythms in the molecular clock, in calcium, and in electrical activity all interact to support the functions of circadian pacemaker neurons. However, the regulatory mechanisms that unify these properties are not defined. Here, we utilize the cellular resolution of th

Sensorimotor coding of vermal granule neurons in the developing mammalian cerebellum

The vermal cerebellum is a hub of sensorimotor integration critical for postural control and locomotion, but the nature and developmental organization of afferent information to this region have remained poorly understoo