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

Abstract

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.