Biology subjects

Quilez, S.

Publications and source records attributed to Quilez, S..

3 recordsLinked to original sources

bioRxiv2021

Molecular and Structural Basis of Olfactory Sensory Neuron Coalescence by Kirrel Receptors

Projections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal IG domains is necessary and sufficient to create homodimers, and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3-/- animals. Our results provide strong evidence for Kirrel3 homodimerization controlling axonal coalescence.

neuroscience↗

bioRxiv2021

Restoration of BDNF-TrkB signaling rescues deficits in a mouse model of SCA6

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in several neurodegenerative diseases, including in post-mortem tissue from SCA6 patients. Here, we show that cerebellar BDNF levels are reduced at an early disease stage in a mouse model of SCA6 (SCA684Q/84Q). One month of voluntary exercise was sufficient to elevate BDNF expression, as well as rescue both motor coordination and cerebellar Purkinje cell firing rate deficits. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF) likewise improved motor coordination and reversed Purkinje cell firing rate deficits, suggesting that exercise acts via BDNF-TrkB signaling. Prolonged chronic 7,8-DHF administration rescued ataxia when treatment commenced near disease onset, but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.

neuroscience↗

bioRxiv2018

Environmental programming of adult foraging behavior in C. elegans

Foraging strategies must be tuned to the availability and distribution of resources in the environment. This can occur over generations and lead to genetic differences in foraging behavior, or it can occur on shorter time scales within an individuals life span. Both genetic and experience-based strategies must be implemented by neural circuits that respond to environmental cues and track internal states, and the analysis of such circuits provides insight into the neural basis of complex decision making. In C. elegans, between-strain genetic differences and within-strain plasticity in foraging has been observed. Most individual changes in foraging are short-term, based on experience over several hours. Here, we tested if developmental experience could permanently alter foraging. We found that in wild strains that are normally highly exploratory, early-life starvation leads to \"cautious\" foraging behavior in which exploration is reduced. We characterize the behavioral bases for these strategies and identify changes in the dynamics of a locomotory circuit involved in navigation. Overall, we show that some C. elegans strains exhibit adaptive tuning of their foraging behavior based on early-life experience, and this is associated with changes in a core navigation circuit.

neuroscience↗