title: Reduced isolation-induced pup ultrasonic communication in mouse pups lacking brain serotonin.
abstract: BACKGROUND
  Serotonin (5-hydroxytryptamine, 5-HT) is a key modulatory neurotransmitter in the mammalian central nervous system (CNS) that plays an important role as a developmental signal. Several lines of evidence associate altered 5-HT signaling with psychopathology in humans, particularly neurodevelopmental disorders such as autism spectrum disorders (ASD). ASD are characterized by persistent social and communication deficits along with stereotyped and repetitive patterns of behavior, with all symptoms emerging early during development.
  
  
  METHODS
  Here, we employed a mouse model devoid of brain 5-HT due to the lack of the gene encoding tryptophan hydroxylase 2 (Tph2), the initial and rate-limiting enzyme of 5-HT synthesis in the CNS. Tph2 null mutant (Tph2 (-/-) ) mice show normal prenatal development; however, they display for yet unknown reasons severe growth retardation during the first postnatal weeks. We investigated, therefore, whether Tph2 (-/-) mice display deficits in isolation-induced ultrasonic vocalizations (USV) as pups during early life. Isolation-induced USV are the most commonly studied behavioral measure to assess developmental delays and communication deficits in rodent models for ASD, particularly as they serve an important communicative function in coordinating mother-pup interactions.
  
  
  RESULTS
  Tph2 (-/-) mouse pups displayed a clear deficit in the emission of isolation-induced USV, as compared to heterozygous and wildtype littermates, exactly during growth retardation onset, including reduced call numbers and deficits in call clustering and temporal organization.
  
  
  CONCLUSIONS
  The ultrasonic communication impairment displayed by Tph2 (-/-) mouse pups is likely to result in a deficient mother-infant interaction, presumably contributing to their growth retardation phenotype, and represents a prominent feature relevant to ASD.
authors.affiliation: Molecular Biology of Peptide Hormones, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13125 Berlin, Germany ; School of Physiology and Pharmacology, University of Bristol, University Walk, BS8 1TD Bristol, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mosienko
authors.affiliation: Molecular Biology of Peptide Hormones, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Beis
authors.affiliation: Molecular Biology of Peptide Hormones, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13125 Berlin, Germany ; St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, D-35032 Marburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wöhr
keywords: Animal models; Autism; Communication; Neurodevelopmental disorders; Serotonin; Ultrasonic vocalizations