Biology subjects

Kuner, T.

Publications and source records attributed to Kuner, T..

3 recordsLinked to original sources

bioRxiv2018

Similarity and strength of glomerular odor representations define neural metric of sniff-invariant discrimination time

The olfactory environment is first represented by glomerular activity patterns in the olfactory bulb. It remained unclear, how these activity patterns intersect with sampling behavior to account for the time required to discriminate odors. Using different classes of volatile stimuli, we investigated glomerular activity patterns and sniffing behavior during olfactory decision-making. Mice discriminated monomolecular odorants and binary mixtures on a fast time scale and learned to increase their breathing frequency at a fixed latency after trial initiation, independent of odor identity. Relative to the increase in breathing frequency, monomolecular odorants were discriminated within 10-40 ms while binary mixtures required an additional 60-70 ms. Intrinsic imaging of odor-evoked glomerular activity maps in anesthetized and awake mice revealed that the Euclidean distance between glomerular patterns elicited by different odors, a measure of similarity and activation strength, was anti-correlated with discrimination time. Therefore, the similarity of glomerular patterns and their activation strengths, rather than sampling behavior, define the extent of neuronal processing required for odor discrimination, establishing a neural metric to predict olfactory discrimination time.

neuroscience↗

bioRxiv2018

Secretory vesicle trafficking in awake and anesthetized mice: differential speeds in axons versus synapses

Neuronal dense core vesicles (DCVs) transport many cargo molecules like neuropeptides and neurotrophins to their release sites in dendrites or axons. The transport properties of DCVs in axons of the intact mammalian brain are unknown. We used viral expression of a DCV cargo reporter (NPY-Venus/Cherry) in the thalamus and two-photon in vivo imaging to visualize axonal DCV trafficking in thalamo-cortical projections of anesthetized and awake mice. We found an average speed of 1 m/s, maximal speeds of up to 5 m/s and a pausing fraction of ~11%. Directionality of transport differed between anesthetized and awake mice. In vivo microtubule +-end extension imaging using Macf18-GFP revealed microtubular growth at 0.12 m/s and provided positive identification of antero- and retrograde axonal transport. Consistent with previous reports, anterograde transport was faster (~2.1 m/s) than retrograde transport (~1.4 m/s). In summary, DCVs are transported with faster maximal speeds and lower pausing fraction in vivo compared to previous results obtained in vitro. Finally, we found that DCVs slowed down upon presynaptic bouton approach. We propose that this mechanism promotes synaptic localization and cargo release.\n\nKey pointsO_LIDespite their immense physiological and pathophysiological importance, we know very little about the biology of dense core vesicle (DCV) trafficking in the intact mammalian brain.\nC_LIO_LIDCVs are transported at similar average speeds in the anesthetized and awake mouse brain compared to neurons in culture, yet maximal speed and pausing fraction of transport were higher.\nC_LIO_LIMicrotubule +-end extension imaging visualized microtubular growth at 0.12 m/s and revealed that DCVs were transported faster in the anterograde direction.\nC_LIO_LIDCV transport slowed down upon presynaptic bouton approach, possibly promoting synaptic localization and cargo release.\nC_LIO_LIOur work provides a basis to extrapolate DCV transport properties determined in cultured neurons to the intact mouse brain and reveal novel features such as slowing upon bouton approach and brain state-dependent trafficking directionality.\nC_LI

neuroscience↗

bioRxiv2017

KCC2-dependent Steady-state Intracellular Chloride Concentration and pH in Cortical Layer 2/3 Neurons of Anesthetized and Awake Mice

Neuronal intracellular Cl- concentration ([Cl-]i) influences a wide range of processes such as neuronal inhibition, membrane potential dynamics, intracellular pH (pHi) or cell volume. Up to date, neuronal [Cl-]i has predominantly been studied in model systems of reduced complexity. Here, we implemented the genetically encoded ratiometric Cl- indicator Superclomeleon (SCLM) to estimate the steady-state [Cl-]i in cortical neurons from anesthetized and awake mice using 2-photon microscopy. Additionally, we implemented superecliptic pHluorin as a ratiometric sensor to estimate the intracellular steady-state pH (pHi) of mouse cortical neurons in vivo. We estimated an average resting [Cl-]i of 6 {+/-} 2 mM with no evidence of subcellular gradients in the proximal somato-dendritic domain and an average somatic pHi of 7.1 {+/-} 0.1. Neither [Cl-]i nor pHi were affected by isoflurane anesthesia. We deleted the cation-Cl- co-transporter KCC2 in single identified neurons of adult mice and found an increase of [Cl-]i to approximately 26 {+/-} 8 mM, demonstrating that under in vivo conditions KCC2 produces low [Cl-]i in adult mouse neurons. In summary, neurons of the brain of awake adult mice exhibit a low and evenly distributed [Cl-]i in the proximal somato-dendritic compartment that is independent of anesthesia and requires KCC2 expression for its maintenance.

neuroscience↗