Parvalbumin interneuron ErbB4 controls ongoing network oscillations and olfactory behaviors in mice

Abstract

AbstractParvalbumin (PV)-positive interneurons modulate the processing of odor information. However, less is known about how PV interneurons dynamically remodel neural circuit responses in the olfactory bulb (OB) and its physiological significance. This study showed that a reinforced odor discrimination task up-regulated the activity of ErbB4 kinase in mouse OB. ErbB4 knock-out in the OB impaired dishabituation of odor responses and discrimination of complex odors, whereas odor memory or adaptation had no alteration in mice. RNAscope analysis demonstrated that ErbB4-positive neurons are localized throughout the OB, whereas within the internal and external plexiform layers, ErbB4 mRNA are largely expressed in PV-positive interneurons. ErbB4 knock-out in PV interneurons disrupted odor-evoked responses of mitral/tufted cells, and led to increased power in the ongoing local field potential in awake mice. We also found a decrease in the frequency of miniature inhibitory postsynaptic currents and deficits in stimulus-evoked recurrent and lateral inhibition onto mitral cells, suggesting broad impairments in inhibitory microcircuit following PV-ErbB4 loss. Similarly, ErbB4 ablation in OB PV interneurons disrupted olfactory discrimination and dishabituation in mice. These findings provide novel insights into the role of PV-ErbB4 signaling in inhibitory microcircuit plasticity, ongoing oscillations, and OB output, which underlies normal olfactory behaviors.