Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal

Abstract

Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim tank. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated.

RIM1α and Interacting Proteins Involved in Presynaptic Plasticity Mediate Prepulse Inhibition and Additional Behaviors Linked to Schizophrenia

“…Moreover, clinical genetic studies have identified genes encoding presynaptic proteins as risk factors for schizophrenia (Karson et al, 1999; Mirnics et al, 2000; Tachikawa et al, 2001; Chen et al, 2004; Lee et al, 2005; Muller et al, 2005; Verma et al, 2005; Kirov et al, 2008; Sudhof, 2008; Walsh et al, 2008; Rujescu et al, 2009). Consistent with these findings, mutation of genes encoding presynaptic proteins has resulted in mouse models relevant to schizophrenia (Drew et al, 2007; Dyck et al, 2007, 2009; Etherton et al, 2009). Thus, we hypothesized that deletion or mutation of the presynaptic protein RIM1α, and its binding partners Rab3A and synaptotagmin, would lead to schizophrenia-related behavioural abnormalities (Powell and Miyakawa, 2006).…”

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

“…This non-preference for novelty was in contrast to other paradigms using a preference for novelty to assess object recognition and episodic memory in mice and rats [17,22,32,70]. Neophobia for novel food, objects, or locations has been well-documented in rodents (see [23,31]), and can be altered by pharmacological challenge [6,26,76], rearing conditions [28], or genetic change [3,18,38,45,57,62]. Nonpreference for novelty has been shown to be strain-dependent in mice [26,34].…”

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

“…Social defects are also common to many mutant mouse models of synaptic dysfunction or schizophrenia susceptibility genes (30,47,70). Surprisingly, during social novelty testing, Bdr mutants from stressed dams spent approximately the same time with the now familiar intruder mouse (Stranger 1) than the new intruder mouse (Stranger 2).…”