Venue: Centre Broca
Language of the defense: english
Tessa Scarabello
IINS
Thesis director: Lisa Roux
Title
Olfaction and Oxytocin in female alloparental behaviors
Abstract
Alloparental behaviors define the set of actions undertaken by adults to insure the survival of other individuals’ progeny such as crouching over the young, retrieval, or parental nesting. The very first encounter with a pup can trigger the emergence of these behaviors in naive virgin mice who had never expressed these behaviors before, and their performances is known to improve upon repeated exposures to pups. Yet, the neurobiological substrates of this phenomenon are still unclear. Previous work highlighted the importance of auditory cues and oxytocin (OT) release in the auditory cortex of virgin females for the establishment of retrieval behavior. In contrast, the role played by olfaction in the transition of mice from naive to efficient caretakers remains so far little explored.
The goal of this work has been to assess the impact of olfaction in the establishment of alloparental behaviors in naive female mice, as well as the influence of oxytocinergic neuromodulation in the main part of the olfactory cortex, the piriform cortex (PIR).
We found that within just a few minutes, naive C57Bl6/J female mice exposed to pups start building a nest to host the pup. However, when the odor of the pup is masked, the onset of nesting in these mice is delayed despite comparable pup investigation times compared to controls. In addition, mice display non-adapted behaviors when they are unable to smell the natural odor of the pup: they favor failed pup retrievals over nest building. Altogether, these first observations suggest that olfaction plays a role in triggering adapted alloparental behaviors upon first pup exposure.
Given the role of OT in social behaviors, we hypothesized that oxytocinergic transmission in the PIR could play a role in alloparental behavior emergence. Using immunochemistry in the Oxtr-3xHA-T2A-iCreERT2 mouse line, we showed that oxytocin receptors (OTR) are mostly expressed in the deep layer III of the PIR, unlike in previous works based on OTR-targeted antibodies. To assess the dynamics of OT signaling in the PIR during our task, and in particular during pup olfactory investigation preceding the start of nesting, we monitored mice with fiber photometry using an OT GRAB sensor expressed in the PIR. This method did not reveal any significant OT level change at the time of pup investigation but we found a slow build-up of OT in the PIR spanning the whole task time course. In contrast, using GCaMP8m expressed in OTR-positive cells, we found that OTR-positive neurons are consistently activated across all pup olfactory investigation events, even though they represent only a small percentage of PIR cells. Altogether, these results indicate that OTR and OT are present in the PIR upon pup exposure, and that they could exert a slow influence on neuronal responses in PIR circuits.
To selectively suppress the expression of OTR in the PIR and test the impact on pup care strategy, we adopted a viral approach to express the cre-recombinase locally in the PIR of Oxtr[flox] mice. Similar to previous experiments with pup odor masking, this local knock-out of the OTR in the PIR impaired pup care strategy, compared to mice injected with a control virus.
To identify the brain-wide circuits involved in this behavioral effect, we used brain-wide activity mapping combined with brain clearing (iDISCO) to compare the brains of naive females exposed for the first time to a pup, with or without a local knock-out of OTR in the PIR. We found striking differences in the activation of the Orbito Frontal Cortex, a region known to participate to sensory processing and decision-making in social contexts. These results suggest that OT in the PIR contributes to gate the neuronal circuits recruited during pup odor exposure, leading to the selection of appropriate behaviors. Altogether, this work paves the way for future research to understand how olfaction and its modulation by OT shapes pup-directed behavioral changes in naive female mice.
Key words: Alloparental behaviors; Oxytocin ; Olfaction
Jury
- Mrs BUONVISO Nathalie, DR, CRNL, Lyon – Spokesperson
- Mrs CARCEA Ioana, AP, Rutgers Brain Health Institute, N.J – Spokesperson
- Mrs MUSCATELLI Françoise, DR, INMED, Marseille – Examinator
- Mr RENIER Nicolas, DR, ICM, Paris – Examinator
- Mrs ROUX Lisa, DR, IINS, Bordeaux – Thesis director
- Mr FERREIRA Guillaume, DR, INRAE, Bordeaux – Invited