From Abnormal Hippocampal Synaptic Plasticity in Down Syndrome Mouse Models to Cognitive Disability in Down Syndrome
Potential impact of altered synaptic plasticity on hippocampal processing in Ts65Dn mouse model of Down syndrome. Schematic of two main pathways through hippocampus arriving from the entorhinal cortex: temporoammonic (TA)—direct to CA1 distal dendrites; trisynaptic pathway from DG through CA3 to proximal CA1 dendrites. LTP and LTD are proposed to minimize interference between the two pathways [50, 131]. (a) In euploid hippocampi, high-frequency inputs induce LTP in CA1 resulting in enhanced suppression of inputs from TA by feed-forward inhibition arising from interneurons in stratum oriens. (b) Low-frequency inputs depress the trisynaptic pathway releasing distal CA1 dendrites from feed-forward inhibition and allowing information to flow through the TA pathway. (c) In Ts65Dn hippocampi, aberrant LTP in CA1 results in diminished feed-forward inhibition during high-frequency activity allowing TA inputs to become superimposed on those flowing through the trisynaptic pathway. (d) Enhanced LTD would be expected to facilitate flow of low-frequency information through the direct TA pathway in Ts65Dn mice.
(a) Euploid: LTP
(b) Euploid: LTD
(c) Ts65Dn: LTP
(d) Ts65: LTD
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