Mitral/tufted cell activity is attenuated and becomes uncoupled from respiration following naris closure.

Patterned neural activity helps to establish neuronal connectivity, produce coding of sensory information, and shape synaptic strengths. Here we demonstrate that normal olfactory bulb development might rely on spatial and temporal patterns of afferent neural activity. Neonatal naris occlusion profoundly impacts the development of the ipsilateral olfactory bulb, including reduced bulb volume, decreased protein synthesis, and increased cell death. Relatively few morphologic changes occur if closure is performed postweaning. We examined the immediate electrophysiological consequences of occlusion across this developmentally sensitive period by recording spontaneous and odor-driven mitral/tufted cell responses while the naris was open, closed, and then reopened. In 1-week-old animals, occlusion severely attenuated spontaneous activity, and presentation of the broad-spectrum odorant amyl acetate failed to evoke responses. In 2- and 4-week old rats, spontaneous activity was also reduced by naris closure. However, some cells remained responsive to concentrated odors, even in animals with transected anterior commissures, suggesting passage of odors across the septal window or retronasal pathways. In all age groups, cellular activity became uncoupled from the respiratory cycle. Approximately 47% (18 of 38) of the mitral/tufted cells exhibited activity that was correlated with respiration in the open-naris state, while only 5% (2 of 38) were coupled during naris closure. These data (a) indicate that naris closure reduces both spontaneous and odor-evoked responses, and (b) provide an electrophysiological correlate to a sensitive period in bulb development. The loss of respiration-related synchrony and the reduced activity of mitral/tufted cells may synergistically contribute to the diverse consequences of naris closure on bulb development.