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

Abstract

Experiences, such as sensory learning, are known to induce plasticity in mammalian sensory systems. In recent years aversive olfactory learning-induced plasticity has been identified at all stages of the adult olfactory pathway; however, the underlying mechanisms have yet to be identified. Much of the work regarding mechanisms of olfactory associative learning comes from neonates, a time point before which the brain or olfactory system is fully developed. In addition, pups and adults often express different behavioral outcomes when subjected to the same olfactory aversive conditioning paradigm, making it difficult to directly attribute pup mechanisms of plasticity to adults. Despite the differences, there is evidence of similarities between pups and adults in terms of learning-induced changes in the olfactory system, suggesting at least some conserved mechanisms. Identifying these conserved mechanisms of plasticity would dramatically increase our understanding of how the brain is able to alter encoding and consolidation of salient olfactory information even at the earliest stages following aversive learning. The focus of this review is to systematically examine literature regarding olfactory associative learning across developmental stages and search for similarities in order to build testable hypotheses that will inform future studies of aversive learning-induced sensory plasticity in adults.

Olfactory Stimulation Regulates the Birth of Neurons That Express Specific Odorant Receptors

“…Observed changes in the relative abundance of specific OSN subtypes have been attributed to the selective lengthening or shortening of neuronal lifespan ( Cadiou et al, 2014 ; Cavallin et al, 2010 ; Jones et al, 2008 ; Morrison et al, 2015 ; Ross and Fletcher, 2019 ; Santoro and Dulac, 2012 ; van der Linden et al, 2018 ; Watt et al, 2004 ; Zhao and Reed, 2001 ; Zhao et al, 2013 ), which is predicted to cause the enrichment or depletion, respectively, of specific OSN subtypes. In theory, changes in the relative abundance of specific OSN subtypes could also occur via selective changes in their rates of neurogenesis.…”

Aversive Learning Increases Release Probability of Olfactory Sensory Neurons

“…This finding suggests that the mechanisms that are involved in downregulating GABA B receptors may not selectively target the conditioned glomerulus only, but rather a small area covering multiple glomeruli. Together with other fear conditioning induced changes in the OB circuit and neuromodulation (3,5), this phenomenon may contribute to olfactory fear generalization (4,33). To test this possibility, future experiments would require activating adjacent glomeruli individually while recording from their postsynaptic cells.…”

“…A p value <0.05 was considered to be significant (* p<0.05, ** p<0.01, *** p<0.001, and **** p<0.0001). (3,77) =15.53, p=6.2E -8 . Each point represents the mean value of four to six trials from a single ET cell.…”

“…Fluorescent intensity of stimulated M72 glomeruli of FC mice was significantly lower than the control M72 glomeruli (the unstimulated glomeruli of FC mice, and both stimulated and unstimulated glomeruli of NFC mice) as compared to their neighboring glomeruli (FC mice: stimulated side 0.87±0.08, n=40 glomeruli vs FC-unstimulated side: 1.18±0.03, n=42 from four mice; NFC mice: stimulated side: 1.22±0.05, n=67 vs NFCunstimulated side: 1.27±0.03, n=117 from four mice). One Way ANOVA with Tukey correction: F (3,265) =10.31, p=1.9E -6 . test, p=1.0E -9 ; n=15) or CGP application, respectively (middle panel for CGP alone: paired t test, p=0.004, n=8; and right panel for CGP + Baclofen: paired t test, p=0.039, n=7).…”

“…Associative learning, the process by which the brain assigns predictive values to sensory stimuli and adjusts behavioral responses, is essential for survival. This process is mediated by neuroplasticity along the sensory pathways as well as in associated cortical and limbic regions (1)(2)(3). Although contributions from altered peripheral sensory inputs into the brain have been implicated (4)(5)(6)(7), the underlying mechanisms remain poorly understood.…”