Thesis defense – Pierre Mortessagne

Name: <span>Thesis defense – </span>Pierre Mortessagne
Start: 2024-12-13T14:30:00+01:00
End: 2024-12-13T14:30:00+01:00

Friday 13 December / 14:30

Venue: Centre Broca

Defense in english

Pierre Mortessagne
Abrous’ team
Neurocentre Magendie

Thesis supervisor: Emilie Pacary

Title

Characterization of the different populations of granular neurons in the dentate gyrus of the hippocampus: from morphology to function

Abstract

In the dentate gyrus (DG) of the hippocampus, the generation of dentate granule neurons (DGNs) starts during late embryogenesis, peaks around birth and continues at low levels during adulthood. This continuous neurogenesis makes the DG a unique structure, composed of DGNs from distinct temporal origins, which form subpopulations potentially bearing unique anatomical characteristics and functional roles in hippocampal physiology. Surprisingly, this hypothesis has received limited attention. In this context, our research aimed to elucidate the morphological, electrophysiological, and behavioral characteristics of DGNs subpopulations based on their temporal origin. Building on prior findings from our team that highlighted dendritic differences between these populations, we focused on examining the features of their axons, called mossy fibers (MFs). Using sparse labeling strategies — electroporation to target embryonically-born (E14.5) and neonatally-born (P0) DGNs, and retroviral injections for adolescent-born (P21) and adult-born (P84) DGNs — we uncovered that DGNs generated later in life develop larger MF boutons with more filopodia, and exhibit a shorter axon initial segment. Additionally, using the Osteocalcin-Cre and Ascl1CreERT2 mouse lines to selectively label large cohorts of embryonically-born and adult-born DGNs, respectively, we found that earlier-born neurons project further onto the CA2 compared to later-born neurons. Following these morphological findings, we further investigated the functional characteristics of temporally distinct DGNs at both the electrophysiological and behavioral levels. The electrophysiological studies revealed similar intrinsic properties between neonatally- and adult-born DGNs, and higher basal transmission in neonatally-born DGNs, potentially reflecting a larger number of active sites. Finally, we examined the role of embryonic-born DGNs in social behavior, and showed that acute inhibition of these neurons delayed the expression of social preference. However, these functional data remain preliminary and need further investigation. Altogether, this PhD work highlights the significant impact of the birthdate of DGNs on their anatomical and potentially functional characteristics, and emphasizes the importance of considering their precise temporal origin in any structural or functional analysis of the DG.

Keywords: Neurogenesis, Dentate Gyrus, Dentate Granule Neurons, Temporal Origin, Axon

Sélection de publications

Mortessagne P, Cartier E, Balia M, Fèvre M, Corailler F, Herry C, Abrous DN, Battefeld A, Pacary E. Genetic labeling of embryonically-born dentate granule neurons in young mice using the PenkCre mouse line. Sci Rep. 2024 Feb 29;14(1):5022. doi: 10.1038/s41598-024-55299-9.

Lods M, Mortessagne P, Pacary E, Terral G, Farrugia F, Mazier W, Masachs N, Charrier V, Cota D, Ferreira G, Abrous DN, Tronel S. Chemogenetic stimulation of adult neurogenesis, and not neonatal neurogenesis, is sufficient to improve long-term memory accuracy. Prog Neurobiol. 2022 Dec;219:102364. doi: 10.1016/j.pneurobio.2022.102364.

Kerloch T, Farrugia F, Bouit L, Maître M, Terral G, Koehl M, Mortessagne P, Heng JI, Blanchard M, Doat H, Leste-Lasserre T, Goron A, Gonzales D, Perrais D, Guillemot F, Abrous DN, Pacary E. The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis. Mol Psychiatry. 2021 Dec;26(12):7280-7295. doi: 10.1038/s41380-021-01301-z.

Lods M, Pacary E, Mazier W, Farrugia F, Mortessagne P, Masachs N, Charrier V, Massa F, Cota D, Ferreira G, Abrous DN, Tronel S. Adult-born neurons immature during learning are necessary for remote memory reconsolidation in rats. Nat Commun. 2021 Mar 19;12(1):1778. doi: 10.1038/s41467-021-22069-4.