Do all mice smell the same? Chemosensory cues from inbred and wild mouse strains elicit stereotypic sensory representations in the accessory olfactory bulb

Abstract

Background For many animals, chemosensory cues are vital for social and defensive interactions and are primarily detected and processed by the vomeronasal system (VNS). These cues are often inherently associated with ethological meaning, leading to stereotyped behaviors. Thus, one would expect consistent representation of these stimuli across different individuals. However, individuals may express different arrays of vomeronasal sensory receptors and may vary in the pattern of connections between those receptors and projection neurons in the accessory olfactory bulb (AOB). In the first part of this study, we address the ability of individuals to form consistent representations despite these potential sources of variability. The second part of our study is motivated by the fact that the majority of research on VNS physiology involves the use of stimuli derived from inbred animals. Yet, it is unclear whether neuronal representations of inbred-derived stimuli are similar to those of more ethologically relevant wild-derived stimuli. Results First, we compared sensory representations to inbred, wild-derived, and wild urine stimuli in the AOBs of males from two distinct inbred strains, using them as proxies for individuals. We found a remarkable similarity in stimulus representations across the two strains. Next, we compared AOB neuronal responses to inbred, wild-derived, and wild stimuli, again using male inbred mice as subjects. Employing various measures of neuronal activity, we show that wild-derived and wild stimuli elicit responses that are broadly similar to those from inbred stimuli: they are not considerably stronger or weaker, they show similar levels of sexual dimorphism, and when examining population-level activity, cluster with inbred mouse stimuli. Conclusions Despite strain-specific differences and apparently random connectivity, the AOB can maintain stereotypic sensory representations for broad stimulus categories, providing a substrate for common stereotypical behaviors. In addition, despite many generations of inbreeding, AOB representations capture the key ethological features (i.e., species and sex) of wild-derived and wild counterparts. Beyond these broad similarities, representations of stimuli from wild mice are nevertheless distinct from those elicited by inbred mouse stimuli, suggesting that laboratory inbreeding has indeed resulted in marked modifications of urinary secretions.

Biological Roles of Lipocalins in Chemical Communication, Reproduction, and Regulation of Microbiota

“…Examples of typical MUP ligands (VOCs) previously studied in mice (Cavaggioni et al, 1987;Novotny et al, 1999;Zidek et al, 1999;Sharrow et al, 2003;Bingham et al, 2004) are presented in Figure 1B. For their complexity (volatiles, non-volatile proteins, and peptides), body secretions are now seen as signature mixtures rather than pheromones (Brennan and Kendrick, 2006;Nagel et al, 2018;Roberts et al, 2018;Bansal et al, 2021).…”

“…These signals are often complex and provide information about multiple states of an individual including (sub-)species, kin, sex, health, and food sources ( Hurst et al, 1997 , 1998 ; Zala et al, 2004 , 2015 ; Cheetham et al, 2007 ; Stopková et al, 2007 ; Bímová et al, 2009 ). Different types of molecules manifest the complexity of such signals which are detected via chemosensory G-protein coupled receptors of the main olfactory epithelia (MOE) and of the vomeronasal organ (VNO; Moss et al, 1997 ; Leinders-Zufall et al, 2000 ; Spehr et al, 2006 ; Wynn et al, 2012 ; Ibarra-Soria et al, 2014a ; Nagel et al, 2018 ; Santoro and Jakob, 2018 ; Van Der Linden et al, 2018 ; Miller et al, 2020 ; Bansal et al, 2021 ). These receptors are tuned to particular signalling molecules including the volatile organic compounds – VOCs ( Berghard and Buck, 1996 ; Malnic et al, 1999 ; Kwak et al, 2012 , 2013 ), short peptides ( Leinders-Zufall et al, 2004 ; Sturm et al, 2013 ) and non-volatile lipocalins, in mice, dominated by the male-biased MUPs ( Chamero et al, 2007 ; Roberts et al, 2012 ).…”

“…For example, lipocalins released from predators (cats, rats) are detected by mice and this induces aversive responses ( Papes et al, 2010 ; Carvalho et al, 2015 ; Pérez-Gómez et al, 2015 ). Together, these secretory signals form signature mixtures, which generate stable representations in the accessory olfactory bulb (AOB) and, in other parts of the brain, these representations are linked to relevant behaviours ( Bansal et al, 2021 ).…”

“…Profound differentiation of VNO and MOE in mice resulted in a highly specialized system being able to detect a wide spectrum of compounds including soluble (V2R) and volatile (V1R) compounds with VNO and general odorants with MOE. The signals detected by VNO are then processed in the AOB which maintain stereotypic sensory representations for broad types of stimuli, providing a substrate for relevant behaviours ( Bansal et al, 2021 ). The responses of VNO and MOE are fast because odours are transported in turbulent plumes from the sites of origin and for example mice are able to detect these dynamically changing odours with a frequency of up to 40Hz ( Ackels et al, 2021 ).…”

Brain-Wide Synaptic Inputs to Aromatase-Expressing Neurons in the Medial Amygdala Suggest Complex Circuitry for Modulating Social Behavior

“…In accord with the role of MeA, and aromatase neurons, in sexually dimorphic social behaviors, the MeA displays structural, molecular, and functional sex differences ( Nishizuka and Arai, 1981 ; De Vries et al, 1984 ; Cooke et al, 1999 ; Morris et al, 2008a ; Bergan et al, 2014 ; Billing et al, 2020 ). In fact, the domestication process of creating isogenic mouse strains may have accentuated sex differences in circuit function ( Chalfin et al, 2014 ; Bansal et al, 2021 ). We found that the broad pattern of regional inputs to aromatase-expressing MeA neurons was conserved across males and females; however, a number of regions displayed a quantitative difference in the percentage of inputs observed in males compared with females.…”