title: Impaired social memories in 129P2 inbred mice are rescued by reduced Csk expression.
abstract: The C-terminal Src kinase (Csk) is an essential signaling factor guiding central nervous system (CNS) development. In the adult brain, Csk-mediated control of Src may also modulate glutamatergic synaptic transmission and N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity. The regulation of N-methyl-d-aspartate (NMDA)-dependent plasticity by a myriad of kinase cascades has been investigated intensively during spatial and fear learning, while little is known about the regulatory kinases and role of NMDA-dependent plasticity during equally critical forms of social learning. We assessed social memory in Csk(+/+) and Csk(+/-) mice backcrossed onto 129P2, an inbred strain with wild-type impairments in social memory. Reduced Csk expression in Csk(+/-) mice was associated with increased NMDAR subunit 2B (NR2B) phosphorylation in the amygdala (AM) and olfactory bulb (OB), and with markedly improved social recognition memory and social transmission of food preference (STFP). In contrast, phosphorylation of NR2B was only slightly increased in the hippocampus of 129P2/Csk(+/-) mice, and the poor spatial object recognition memory of wild-type 129P2/Csk(+/+) mice was not rescued by reduced Csk expression. The Csk pathway appears to be a critical signaling cascade regulating social learning and memory, and presents a possible therapeutic target in diseases such as autism that are characterized by aberrant social behaviors.
authors.affiliation: Mount Sinai Hospital, Toronto, ON, Canada. sinai@lunenfeld.ca
authors.forename: L
authors.initials: L
authors.lastname: Sinai
authors.forename: R
authors.initials: R
authors.lastname: Mathew
authors.forename: J C
authors.initials: JC
authors.lastname: Roder
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D000081247:CSK Tyrosine-Protein Kinase; D002755:Choice Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D009473:Neuronal Plasticity / Q000502:physiology; D009830:Olfactory Bulb / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology*; D012919:Social Behavior; D009435:Synaptic Transmission / Q000502:physiology; D019061:src-Family Kinases
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases