CELL-DEPENDENT SYNAPTIC PLASTICITY ALTERATION IN THE SUBICULUM AT AN EARLY STAGE OF ALZHEIMER'S DISEASE

Memory processes involve long- and short-term synaptic plasticity within the hippocampus. While plasticity at CA3-CA1 synapses has been extensively studied, little is known at CA1-Subiculum (SUB) connections. SUB is one of the major outputs of the hippocampal formation with two main types of pyramidal cells, bursting and regular-spiking neurons, preferentially participating in spatial and episodic memory, respectively. Because this structure is also one of the earliest brain regions affected in Alzheimer's disease (AD), it is first important to assess the mechanisms involved in synaptic plasticity at CA1-SUB glutamatergic synapses and then investigate whether it is impaired at an early stage of the disease. Using patch-clamp recordings, we observed that long-term potentiation (LTP) induction in bursting neurons partially involves N-methyl-D-aspartate and kainate receptors activation, while LTP induction in regular-spiking neurons does not appear to require these glutamate receptors. In a 6-7 months triple transgenic (3xTg) mice model of AD, known to display early learning and memory deficits, LTP was impaired in regular-spiking but not in bursting neurons. Intriguingly, short-term synaptic plasticity seems to be altered in both subicular cell types in this model. All together, these results indicate that pyramidal subicular neuron subtypes differ in their information processing mechanism, and exhibit a distinct alteration at an early stage of AD. The mechanisms underlying this specificity remain to be investigated.