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

Abstract: 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 behavioural 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 odour and mixtures that had the same monomolecular odour and a small amount of a structurally similar odour. The impairments did not occur for less similar odour pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odour 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 odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations. (Figure presented.). Key points: The output mitral cells (MCs) of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioural and physiological relevance of these gap junctions is not well understood. In studies conducted in Cx36 knockout (KO) mice, we found impaired odour discrimination vs. wild-type mice in a go/no-go associative learning task, although deficits only occurred with the most difficult tasks involving odour mixtures. These results provide the first evidence to date of olfactory behavioural deficits in Cx36 KO mice. In OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, but only during latter stages of the response. We suggest that KO-induced impairments in fine odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations.