Changes in functional connectivity between the basolateral amygdala and ventral hippocampus in the 3xTgAD mouse in vivo

The cognitive deficits seen in Alzheimer's disease (AD) are linked to pathological changes in the medial temporal lobe. To determine the functional consequences of AD, we examined amygdala-hippocampal synaptic transmission in urethane-anaesthetized control (n=4; 3-7 months old) and triple-transgenic Alzheimers disease mice (3xTgAD; n=4; 7 months old). Multi-electrode arrays recorded laminar responses across ventral CA1 and dentate gyrus (DG). A twisted, bipolar stimulating electrode was placed in the basolateral amygdala (BLA). Stimulus intensities were set to 50% of the maximal evoked response. Evoked local field potentials (LFPs) in CA1 consisted of two sequential components; CSD analyses located the initial response as a current sink in CA1 oriens/pyramidale with the later component as a sink in lacunosum moleculare. Thus, the early LFP likely reflects activation of the monosynaptic connection from BLA to CA1 (direct), whilst the later LFP may represent activation of CA1 from BLA via entorhinal cortex (EC) layer III (indirect). BLA-evoked LFPs were also observed in DG in all mice, transmitted perhaps via EC layer II. The direct LFP latency in CA1 was significantly shorter in 3xTgAD mice compared to controls. In addition, input-output curves for the direct response tended to show smaller LFPs for the 3xTgAD mice compared to controls (stimuli 200-500microA; responses below 200microA were similar). The indirect response in CA1 and DG tended to be delayed in 3xTgAD mice compared to controls. The 3xTgAD mice also showed a pronounced population spike in DG which was not seen in control mice. Overall, there appears to be a reduced connectivity for the direct BLA input to CA1 in the 3xTg mouse; however, the postsynaptic response in the 3xTg is faster, perhaps indicating a change in CA1 to compensate for a reduced BLA input. The indirect response in 3xTg mice appears at a longer latency in CA1 and DG, but is of relatively greater impact in 3xTg DG compared to controls. This indicates a hyper-excitable state in the BLA-EC-DG pathway in the 3xTgAD mouse. Thus, there appears to be a complex set of changes in the latency and magnitude of synaptic connections within the ventral hippocampal formation of the 3xTgAD mouse.