ETD system

Electronic theses and dissertations repository

 

Tesi etd-01132017-111932


Thesis type
Tesi di dottorato di ricerca
Author
BERTERO, ALICE
URN
etd-01132017-111932
Title
Mapping the structural and functional organization of the serotonergic system connectome
Settore scientifico disciplinare
BIO/06
Corso di studi
BIOLOGIA
Commissione
tutor Prof. Pasqualetti, Massimo
commissario Prof. Peretto, Paolo
commissario Caleo, Matteo
commissario Prof. Vignali, Robert
commissario Bifone, Angelo
commissario Dott. Bifone, Angelo
commissario Dott. Gozzi, Alessandro
Parole chiave
  • Serotonin
  • Retrograde tracing
  • Rabies virus
  • Connectome
Data inizio appello
15/02/2017;
Consultabilità
parziale
Data di rilascio
15/02/2020
Riassunto analitico
Serotonin-synthetizing neurons, which are confined in the raphe nuclei of the rhombencephalon, provide a profuse innervation network throughout the central nervous system and are involved in the modulation of a plethora of brain functions. In the last few years, the development of novel genetic tools and high-throughput techniques has added unforeseen degrees of heterogeneity among serotonergic neurons in terms of neurodevelopmental origins, gene programs and electrophysiological properties. Recently, a map of the complex topographical organization of the serotonergic fibers has been drawn using intersectional fate mapping strategy, as well as retrograde or anterograde tracing. However, no comprehensive retrograde study has been performed yet, and anterograde approaches still set a series of limitation. Here, combining the recombinant G-deleted rabies virus system with Tph2GFP knock-in mice, in which serotonergic neurons were clearly labeled by the expression of GFP, I present a map of the topographic organization of 5-HT ascending projection to 19 rostral brain regions, known to be regulated by 5-HT. This experimental approach revealed that each brain district hereby investigated is innervated by a relatively small and region-specific number of serotonergic neurons. Thanks to Cre-independent and -dependent monosynaptic tracing, coupling pseudotyped recombinant rabies virus with a helper adeno-associated virus, it was possible to deduce that such narrow subpopulation of 5-HT neurons is characterized by a wiring transmission mode. Moreover, the balance between wiring and volume transmission appears to be region-specific, and may underlie specific regulation mechanism on neuronal functions. Altogether, my results can shed new lights on the communication properties of the serotonergic system, highlighting a further level of serotonergic control of brain function, possibly helping to better understand its role in health and disease.
File