Impaired learning and memory in CD38 null mutant mice

Abstract

CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca2+ from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38−/−) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory. Although ASD and learning deficits commonly co-occur, the role of CD38 in learning and memory has not been investigated. We report that CD38−/− mice show deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test. However, either long-term potentiation or long-term depression is not impaired in the hippocampus of CD38−/− mice. Our results provide convincing evidence that CD38−/− mice show deficits in various learning and memory tasks including spatial and non-spatial memory tasks. Our data demonstrate that CD38 is critical for regulating hippocampus-dependent learning and memory without modulating synaptic plasticity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0195-5) contains supplementary material, which is available to authorized users.

CD38 positively regulates postnatal development of astrocytes cell-autonomously and oligodendrocytes non-cell-autonomously

“…CD38 has been shown to promote the secretion of oxytocin from hypothalamic neurons and insulin from pancreatic beta cells (Jin et al, ; Kato et al, ). Consistently, Cd38 −/− mice displayed impaired glucose tolerance, poor parental behavior, poor social recognition memory, and deficits in learning and memory (Jin et al, ; Kato et al, ; Kim et al, ). Indeed, reduced expression levels of CD38 have been shown in lymphoblastoid cell lines from patients with autism, and genetic variation at a locus of CD38 has also been associated with autism spectrum disorders (ASD) (Higashida, Yokoyama, Kikuchi, & Munesue ; Higashida et al, ; Lerer et al, ; Munesue et al, ).…”

Pre- and post-synaptic roles for DCC in memory consolidation in the adult mouse hippocampus

“…While high-frequency tetanus-induced LTP has been considered as an experimental model of the neuronal changes that underlie learning and memory, recent studies provide evidence for possible functional dissociations between this form of synaptic plasticity and behavioural performance on spatial memory tasks. Indeed, memory deficits in the Morris Water Maze can be associated with no appreciable change in LTP induction or expression [58,59]. Here, we identified a significant deficit in Barnes maze spatial performance in R4ag11-Cre/DCC fl/fl mice, with no change in LTP induction at the Schaffer collateral synapse in vitro, whereas animals lacking DCC in CA3 neurons exhibited no deficit in Barnes maze performance, yet did show impaired LTP.…”

Age- and Sex-Specific Fear Conditioning Deficits in Mice Lacking Pcdh10, an Autism Associated Gene

“…Like Pcdh10 +/mice, several mouse models associated with ASD exhibit fear conditioning deficits, including CD38, Homer1a, and Scn1a mutants (Han et al, 2012;Banerjee et al, 2016;Kim et al, 2016), as well as a number of others (Markram et al, 2008;Stapley et al, 2013;Howell et al, 2017;Nolan et al, 2017;Fricano-Kugler et al, 2019). Reports of fear conditioning in individuals with ASD have been varied, with some reporting impairments, and some failing to find differences compared to controls (Bernier et al, 2005;Gaigg and Bowler, 2007;Sterling et al, 2013).…”

“…Pcdh10 +/males are known to have abnormalities in the BLA and deficits in social behaviors that engage the BLA (Ferri et al, 2015;Schoch et al, 2017). This raises the question of whether Pcdh10 +/males might have deficits in fear conditioning, a behavior that involves the BLA (Ressler and Maren, 2019), and that is disrupted in several in mouse models relevant to ASD (Han et al, 2012;Banerjee et al, 2016;Kim et al, 2016), and in autistic humans (Gaigg and Bowler, 2007;Top Jr. et al, 2016). We hypothesized that fear conditioning would be disrupted in Pcdh10 +/mice, and we tested juvenile and adult male and female Pcdh10 +/and WT littermate mice in both contextual and cued fear conditioning paradigms.…”