Ablation of microRNAs in VIP⁺ interneurons impairs olfactory discrimination and decreases neural activity in the olfactory bulb

Abstract

Aim: MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP + ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP + interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP + miRNA affects olfactory

Does miRNA ablation in VIP+ interneurons of the olfactory bulb impair olfaction?

“…Moreover, tetrode single unit recordings from the M/T layer after Dicer ablation in VIP+ INs in awake head‐fixed mice demonstrated decreased odour‐evoked firing in M/Ts. Finally, Wu et al 1 showed that Dicer ablation restricted to the OB produced similar results.…”

“…This is an interesting and relevant topic related to how genes affect brain circuits and behaviour in health and disease. In the present volume of Acta Physiologica , Wu et al 1 addressed this question using a multi‐technique approach.…”

“…Wu et al 1 ablated Dicer, an RNase III protein that cleaves double‐stranded RNAs into miRNAs, to disrupt miRNA expression in postmitotic VIP+ INs and performed a sequence of experiments to assess the behavioural and circuit consequences of this cell‐specific miRNA ablation. Both odour detection in a food‐seeking task and odorant discrimination in a go‐no‐go associative learning task were disrupted by miRNA ablation.…”

The Response Dynamics and Function of Cholinergic and GABAergic Neurons in the Basal Forebrain During Olfactory Learning

“…The animal training and behavioral tasks were carried out using methods similar to our previous studies (Wang et al, 2022 ; Wu et al, 2022 ). For fiber photometry recordings, head-fixed mice were trained on an air-supported free-floating Styrofoam ball which allowed the mice to maneuver.…”

“…To explore the influence of cholinergic neurons' inactivation on odor discrimination, we conducted an odor discrimination assay that lasted for 9 days, including the training period (2 days), the easy task (3 days), and the difficult task (4 days) in freely moving mice. As in our previous study (Sun et al, 2019;Wang et al, 2022;Wu et al, 2022), mice were first trained to undergo a go/go task, then the mice were trained to perform a go/no-go task, including the easy task (S+: isoamyl acetate; S−: 2-heptanone) and a difficult task (S+: isoamyl acetate: 2-heptanone = 6:4; S−: 2-heptanone: isoamyl acetate = 6:4; Figure 7E). The percent correct rate during the go/no-go task was compared between experimental (Gi + CNO) and control (Gi + saline, mCherry + CNO) animals.…”