SOCIAL COGNITION DEFICITS IN THE J20 MOUSE MODEL OF ALZHEIMER’S DISEASE

The hippocampal CA2 subregion plays a major role in regulating social behaviors, and CA2 dysfunction has been implicated in several neuropsychiatric disorders, including epilepsy and different forms of dementia. Here, we explore CA2 function and related behaviors in a mouse genetic model of Alzheimer’s disease, the J20 line. We found that male and female J20 mice show increased mobility in an open field test, in line with the previously reported hyperactivity phenotype, as well as relatively normal levels of sociability. We then subjected the mice to a CA2-dependent social novelty recognition task, in which a subject mouse explores an arena containing a novel conspecific and a previously encountered conspecific confined to separate wire cup cages. Social memory is manifested by the subject's preference to explore the novel mouse. Male J20 mice show a significant impairment in this task. Strikingly, age-matched female J20 mice show a normal social memory behavior. To understand the mechanisms underlying the differences encountered within the J20 group, we collected the brains of the mice subjected to behavioral tests to measure the expression of cellular markers that could be associated with their performance. In electrophysiological experiments, we have not observed a significant alteration in either the intrinsic electrophysiological properties of CA2 pyramidal neurons or in the amplitude of excitatory or inhibitory synaptic potentials evoked by electrical stimulation of the hippocampal or cortical inputs to CA2. Future experiments will explore whether the deficit in social memory is associated with altered in vivo activity of CA2 neurons.