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Urban, N. N.

Publications and source records attributed to Urban, N. N..

4 recordsLinked to original sources

Fast-spiking interneuron detonation drives high-fidelity inhibition in the olfactory bulb

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection cells, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition.

neuroscience↗

Cell and circuit origins of fast network oscillations in the mammalian main olfactory bulb

Neural synchrony generates fast network oscillations throughout the brain, including the main olfactory bulb (MOB), the first processing station of the olfactory system. Identifying the mechanisms synchronizing neurons in the MOB will be key to understanding how network oscillations support the coding of a high-dimensional sensory space. Here, using paired recordings and optogenetic activation of glomerular sensory inputs in MOB slices, we uncovered profound differences in principal mitral cell (MC) vs. tufted cell (TC) spike-time synchrony: TCs robustly synchronized across fast- and slow-gamma frequencies, while MC synchrony was weaker and concentrated in slow-gamma frequencies. Synchrony among both cell types was enhanced by shared glomerular input but was independent of intraglomerular lateral excitation. Cell-type differences in synchrony could also not be traced to any difference in the synchronization of synaptic inhibition. Instead, greater TC than MC synchrony paralleled the more periodic firing among resonant TCs than MCs and emerged in patterns consistent with densely synchronous network oscillations. Collectively, our results thus reveal a mechanism for parallel processing of sensory information in the MOB via differential TC vs. MC synchrony, and further contrast mechanisms driving fast network oscillations in the MOB from those driving the sparse synchronization of irregularly-firing principal cells throughout cortex.

neuroscience↗

Lateralized decrease of parvalbumin+ cells in the somatosensory cortex of ASD models is correlatedwith unilateral tactile hypersensitivity

Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin expressing (PV+) basket cells (BC) are a major player in maintaining the balance between excitation (E) and inhibition (I) in the cortex. Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorders (ASD) and may contribute to sensory alterations seen in ASD. Here, we report a lateralized decrease in the number of PV+ BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of adult Shank3-/- and Cntnap2-/- mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animals dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (i.e., VVA) showed that the number of BCs was not different but rather, some BCs did not express detectable levels of PV (PV-), resulting in an elevated number of PV- VVA+ basket cells. This lateralized reduction was not observed in the number of interneurons from the other two major groups that express somatostatin or the serotonergic receptor 5HT3a. Finally, we showed that dominant hind paws had higher mechanical sensitivity (i.e., lower mechanical thresholds measured with von Frey test) but no difference in thermal sensitivity (measured with Hargreaves test) when compared to the other hind paw. This mechanical hypersensitivity in the dominant paw correlated with the decrease in the number of PV+ interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the sensory hypersensitivity in ASD could be due to decreased inhibitory inputs to the dominant somatosensory cortex.

neuroscience↗

Mice follow odor trials using stereo olfactory cues and rapid sniff to sniff comparisons

Animals use the distribution of chemicals in their environment to guide behaviors essential for life, including finding food and mates, and avoiding predators. The presence of this general class of behavior is extremely widespread, even though the olfactory sensory apparatus and strategies used may vary between animals. The strategies and cues used by mammals to localize and track odor sources have recently become of interest to neuroscientists, but are still poorly understand. In order to study how mice localize odors, we trained mice to perform a trail following task using a novel behavioral paradigm and behavioral monitoring setup. We find that mice, in order to follow an odor trail, use both sniff by sniff odor concentration comparisons and internares comparisons to guide their behavior. Furthermore, they employ olfactory information to guide adaptive behaviors with remarkably short latencies of approximately 80ms. This study and its findings establish a rich, quantifiable olfactory localization behavior in mice that is amenable to physiological investigations and motivates investigation into the neural substrates of the identified olfactory cues.\n\nSignificanceMany animals, like rodents, rely heavily on their sense smell to guide them as they navigate their environment, to find food and mates and to avoid predators. Yet, in mammals, this function of the olfactory system is much less well studied than odor identification. We created a behavioral task where mice had to follow odor trails in order to efficiently find food and then tracked their movements around those trails. We found that they respond to sniff-by-sniff changes in odor intensity, using those changes to guide movements in less than one tenth of a second and also confirm that they use stereo cues to guide behavior. These results lay the groundwork for determining the brain circuits underlying olfactory navigation.

animal behavior and cognition↗