Anterior thalamic nucleus inputs to the retrosplenial cortex are unperturbed in the hAPP-J20 mouse model of Alzheimer’s disease

Abstract Alzheimer’s disease is a neurodegenerative condition characterised by progressive loss of memory and general decline in cognitive function. Although research has traditionally focused on the hippocampus and entorhinal cortex, other regions important for memory and spatial navigation, such as the anterior thalamic nuclei and retrosplenial cortex, are also affected. The retrosplenial cortex is an important brain region for both memory and spatial navigation, and displays dysfunction in humans during prodromal phases of Alzheimer’s Disease. The anterior thalamic nuclei provide a major input to the retrosplenial cortex, with loss of this input to the retrosplenial cortex causing a dramatic reduction in the expression of the immediate early gene product c-Fos. The anterior thalamic nuclei to retrosplenial cortex connection may thus present a new target for therapeutic intervention in Alzheimer’s Disease. Here, we set out to determine whether Alzheimer’s-like pathology perturbed projections from the anterior thalamic nuclei to retrosplenial cortex in the hAPP-J20 amyloidopathy mouse model, using optogenetic activation of thalamic inputs combined with ex vivo patch clamp electrophysiology. We found that the retrosplenial cortex displayed an age-dependent decline in basal c-Fos activity, with no additional effect of amyloid pathology on c-Fos expression. At all time points (3, 6 and 9 months) measured, we found no evidence of impairments in the synaptic strength or efficacy of the anterior thalamic nuclei projections to either granular or dysgranular subdivisions of the retrosplenial cortex. We conclude that, in the hAPP-J20 mouse model, this pathway is unaffected by amyloid-β overexpression.