An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice

Abstract

Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and parenting. Importantly, mice can be trained to associate novel odors with specific behavioral responses to provide insight into olfactory circuit function. This protocol details the procedure for training mice on a Go/No-Go operant learning task. In this approach, mice are trained on hundreds of automated trials daily for 2–4 weeks and can then be tested on novel Go/No-Go odor pairs to assess olfactory discrimination, or be used for studies on how odor learning alters the structure or function of the olfactory circuit. Additionally, the mouse olfactory bulb (OB) features ongoing integration of adult-born neurons. Interestingly, olfactory learning increases both the survival and synaptic connections of these adult-born neurons. Therefore, this protocol can be combined with other biochemical, electrophysiological, and imaging techniques to study learning and activity-dependent factors that mediate neuronal survival and plasticity.

Single-Cell RNA-Seq of Mouse Olfactory Bulb Reveals Cellular Heterogeneity and Activity-Dependent Molecular Census of Adult-Born Neurons

“…To block olfactory sensory input, we performed unilateral naris occlusion, with the occluded side serving as the sensory-deprived sample and the open side as the control ( Najbauer and Leon, 1995 ; Quast et al, 2017 ; Yamaguchi and Mori, 2005 ). Mice were trained to discriminate various odorants using an olfactory-cued learning paradigm ( Liu et al, 2017 ; Liu et al, 2018 ). This form of olfactory training exposed mice to several different odorants while also actively engaging the olfactory system to facilitate olfactory-discrimination learning.…”

“…The opposite side of the tube was cut beveled for insertion into the nasal cavity. For increased olfactory activity, we implemented a previously described olfactory cued learning paradigm ( Liu et al, 2017 ; Liu et al, 2018 ) where water deprived animals were trained to discriminate a water reward associated odor (S+) from a no reward associated (S−) odor. In brief, animals were trained to poke their nose into an odor delivery port to receive a water reward.…”

Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat

“…Mice were trained 5 days per week in the two-choice operant paradigm wherein one olfactory stimulus was paired with the reinforcer (Figure 3A). Odorants were used at response sites to aid in stimulus discrimination (65) and mask any odor which may be present in reinforcers, which could otherwise bias response learning (66). Reward-paired scent was randomly assigned and counterbalanced across subjects, and target location was randomized between trials to preclude locationbased learning.…”

Olfactory Detection Thresholds for Primary Aliphatic Alcohols in Mice

“…Primary aliphatic alcohols are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination, and assess odor-structure activity relationships in mice (e.g., Sato et al 1994 ; Malnic et al 1999 ; Inaki et al 2002 ; Laska et al 2008 ; Johnson et al 2009 ; Xu and Wilson 2012 ; Iurilli and Datta 2017 ; Liu et al 2018 ). The stimulus concentrations used in these studies vary widely as no systematic survey of the relative sensitivity to these odorants exists in this species.…”