Learning-Dependent and -Independent Enhancement of Mitral/Tufted Cell Glomerular Odor Responses Following Olfactory Fear Conditioning in Awake Mice

Abstract

Associative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected male and female mice expressing the fluorescent calcium indicator GCaMP3 in olfactory bulb mitral and tufted cells to a classical olfactory fear conditioning paradigm. We then used awake, calcium imaging to quantify learning-induced changes in glomerular odor responses, which constitute the first site of olfactory processing in the brain. The results demonstrate that odor-shock pairing nonspecifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and nonconditioned odors, potentially priming the system toward generalization of learned fear. Additionally, CS-specific glomerular enhancements remain even when associative learning is blocked, suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings. In the olfactory bulb (OB), odors are uniquely coded in a spatial map that represents odor identity, making the OB a unique model system for investigating how learned fear alters sensory processing. Classical fear conditioning causes fear of the conditioned stimulus (CS) and of neutral stimuli, known as generalization. Combining fear conditioning with fluorescent calcium imaging of OB glomeruli, we found enhanced glomerular responses of the CS as well as neutral stimuli in awake mice, which mirrors fear generalization. We report that CS and neutral stimuli enhancements are, respectively, learning-independent and learning-dependent. Together, these results reveal distinct mechanisms leading to enhanced OB processing of fear-inducing stimuli and provide important implications for altered sensory processing in fear generalization.

Complex neural representation of odour information in the olfactory bulb

“…Both spatial and temporal coding strategies face the challenge that odour perception is dynamic and varies under different brain states. Wakefulness, attention, experience, metabolism status and the value of the odour for the subject are important factors that can change the perception of the same odour . The underlying mechanisms by which the OB represents odour information precisely under different brain and behavioural states remain elusive, although recent studies have provided relevant data and some hypotheses have been established .…”

Aversive learning-induced plasticity throughout the adult mammalian olfactory system: insights across development

“…Olfactory aversive learning induces changes in sensory coding in the adult mammalian olfactory pathway, a fact we have known for several decades (Bressler 1988;Coopersmith et al 1986;Freeman and Schneider 1982;Pager and Royet 1976), yet we have barely begun to scratch the surface as to the mechanisms underlying neural plasticity responsible for such changes. In recent years, altered coding has been reported across all stages of the adult olfactory pathway including olfactory sensory neurons (OSN) (Kass et al 2013), olfactory bulb (OB) cells (Fletcher 2012;Kass and McGann 2017;Ross and Fletcher 2018), and piriform cortex (PCx) cells (Chen et al 2011;Sevelinges et al 2004); however, extensive investigation of electrophysiological or molecular mechanisms or widespread network alterations underlying the observed coding changes is still lacking in adults. Instead, much of the work regarding mechanisms of olfactory associative learning comes from neonates; however, most of this information regarding odor learning in pups comes from a time point before which the brain or olfactory system is fully developed.…”

The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application

“…The features on the sensory neuron side are, for example, the number of olfactory neurons that carry the specific olfactory receptor for the detection of a specific type of odor. The features that produce individual differences are, for example, previous experiences with the odor in past generations [36,37] and during the individual's life [38,39]. Physiological conditions, such as estrous status, also affect the olfactory sense, indicating that neuromodulators or hormones affect olfactory ability and acuity [40,41] ( Figure 1C).…”