Biology subjects

Pouille, F.

Publications and source records attributed to Pouille, F..

2 recordsLinked to original sources

bioRxiv2025

Connexin 36-mediated gap junctions contribute to fine odor discrimination and excitation of mitral cells in the mouse olfactory bulb

Key PointsO_LIThe output MCs of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioral and physiological relevance of these gap junctions is not well understood. C_LIO_LIIn studies conducted in Cx36 knock-out (KO) mice, we found that the mice displayed reduced fine odor discrimination capabilities versus wild-type mice in a go/no-go associative learning task. These results provide the first evidence to date of olfactory behavioral deficits in Cx36 KO mice. C_LIO_LIIn OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, especially during latter stages of the response. C_LIO_LIWe suggest that KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations. C_LI The output mitral cells (MCs) and tufted cells (TCs) of the mammalian olfactory bulb (OB) are coupled through both chemical mechanisms as well as gap junctions that are mediated by connexin 36 (Cx36). Here we tested both behavioral and physiological effects of eliminating gap junctions in knockout (KO) mice with homozygous deletions of Cx36. In a go/no-go associative learning task, Cx36 KO mice were found to display reduced discrimination capabilities when presented with pairs of stimuli that included a monomolecular odor and mixtures that had the same monomolecular odor and a small amount of a structurally similar odor. The impairments did not occur for less similar odor pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odor discrimination. In physiological recordings in OB slices from Cx36 KO mice, MCs displayed reduced excitation in response to electrical stimulation of sensory afferents, both single stimulus pulses as well as a theta burst pattern designed to mimic sniffing. The reduction in MC excitatory current was most prominent for late portions of their response, 300 ms after single stimulus pulses or following all theta bursts that came after the first. More global local field potentials recorded in OB glomeruli were largely unaffected by Cx36 KO. We suggest that the KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations.

neuroscience↗

bioRxiv2023

Hyperexcitability in the olfactory bulb and impaired fine odor discrimination in the Fmr1 KO mouse model of fragile X syndrome

Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders in humans. FXS is caused by loss of expression of the Fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here we conducted experiments in wild-type and Fmr1 KO (Fmr1-/y) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) in Fmr1 KO mice displayed greatly enhanced excitation, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of LLDs did not appear to reflect changes in inhibitory connections onto MCs but rather enhanced spontaneous excitation of external tufted cells (eTCs) that provide feedforward excitation onto MCs within glomeruli. In addition, in a go/no-go operant discrimination paradigm, we found that Fmr1 KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the higher excitability of MCs in Fmr1 KO mice may impair fine odor discrimination by broadening odor tuning curves of MCs and/or altering synchronized oscillations through changes in transient inhibition. Significance StatementFragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-used Fmr1 knockout (KO) mouse model of FXS. Our studies indicate that Fmr1 KO alters the local excitation/inhibition balance in the bulb - similar to what Fmr1 KO does in other brain circuits - but through a novel mechanism that involves enhanced feedforward excitatory drive. Furthermore, Fmr1 KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by enhanced neural excitability.

neuroscience↗