ImprintedRasgrf1expression in neonatal mice affects olfactory learning and memory

Abstract

Rasgrf1 is genomically imprinted; only the paternally inherited allele is expressed in the neonatal mouse brain until weaning, at which time expression becomes biallelic. Whereas Rasgrf1 has been implicated in learning and memory via knockout studies in adult mice, the effect of its normal imprinted expression on these phenotypes has not yet been examined. Neonatal mice with experimentally manipulated patterns of imprinted Rasgrf1 expression were assessed on an associative olfactory task. Neonates lacking the normally expressed wild-type paternal allele exhibited significant impairment in olfactory associative memory. Adult animals in which neonatal imprinting had been manipulated were also behaviorally assessed; while neonatal imprinting significantly affects body weight even into adulthood, no learning and memory phenotype attributable to imprinting was observed in adults. Additional analyses of neonates showed imprinted Rasgrf1 transcript selective to olfactory bulb even in mice that were null for Rasgrf1 in the rest of the brain and showed that Rasgrf1 affects Ras and Rac activation in the brain. Taken together, these results indicate that Rasgrf1 expression from the wild-type paternal allele contributes to learning and memory in neonatal mice.

Neurobiology of secure infant attachment and attachment despite adversity: a mouse model

“…Though previous work has shown that infant mice display preferences for maternal and homecage odors (Logan et al 2012; Thomas et al 2010) and are able to form conditioned memories (Akers et al 2012; Alleva & Calamandrei 1986; Bollen et al 2012; Bouslama et al 2005; Drake et al 2011; Durand et al 2003; Nagy et al 1972; Wiedenmayer et al 2000), to our knowledge, our data here are the first to show preference learning in infant mice despite an aversive conditioning paradigm, and thus are first to illustrate a sensitive period for attachment-based learning. Similar to developing rats, infant mice display a stress hyporesponsive period (Cirulli et al 1994; D’Amato et al 1992; Schmidt et al 2003).…”

No Evidence for a Parent-of-Origin Specific Differentially Methylated Region Linked to RASGRF1

“…The reason behind using 1000 bp up- and downstream was that tandem repeats associated with ICRs are either found within or adjacent to the ICRs (Thorvaldsen et al, 1998; Okamura et al, 2000; Takada et al, 2002). The repeats associated with Rasgrf1 in mice are found within the ICR (Brideau et al, 2010). …”

Dynamics of murine brain protein synthesisin vivoidentify the hippocampus, cortex and cerebellum as highly active metabolic sites

“…Qki (KH domain containing RNA binding) is a RNA-binding protein that influences glial cell fate and development (Hardy, 1998), but also plays an essential role in myelinisation processes, since spontaneous mutations in this protein result in hypomyelinization of the central and peripheral nervous systems (Hardy et al, 1996, Lu et al, 2003, Larocque and Richard, 2005. Rasgrf1 (Ras protein-specific gunine nucleotidereleasing factor1) is a guanine nucleotide exchange factor (GEF) that promotes dissociation of GDP from RAS protein in the brain in response to Ca 2+ influx, muscarinic receptor signalling, or activation of the G protein beta-gamma subunit, and appears crucial for long-term memory formation in mouse model systems (Drake et al, 2011, Barman et al, 2014, Manyes et al, 2018. Atxn10 (Ataxin 10) is a cytoplasmic protein required for neuron survival, differentiation and neuritogenesis via activation of mitogen-activated protein kinase cascade (Marz et al, 2004, Waragai et al, 2006.…”