Impairment of Hippocampal CA1 Heterosynaptic Transformation and Spatial Memory by β-Amyloid25–35

Miao-Kun Sun, Daniel L. Alkon
2002 Journal of Neurophysiology  
Sun, Miao-Kun and Daniel L. Alkon. Impairment of hippocampal CA1 heterosynaptic transformation and spatial memory by ␤-amyloid 25-35 . J Neurophysiol 87: 244125-35 . J Neurophysiol 87: -244925-35 . J Neurophysiol 87: , 2002 10.1152/jn.00230.2001. In Alzheimer's disease, the cholinergic damage (reduced neurotransmission) and cognitive impairment occur long before ␤-amyloid (A␤) plaque formation. It has not been established whether the link between soluble A␤ and cholinergic functions contributes
more » ... nctions contributes to synaptic dysfunction that underlies the cognitive impairment. Here, we report that A␤ 25-35 , an active form of A␤, inhibited long-term synaptic modification that depends on the associative activation of cholinergic and GABAergic inputs when bilaterally injected intracerebroventricularly (icv; 200 g/site). The A␤ microinjections did not affect single-pulse-evoked glutamatergic and GABAergic synaptic transmission onto the hippocampal CA1 pyramidal cells, while cholinergic intracellular was dramatically reduced by the A␤ 25-35 injection. Spatial memory of the water maze task was also impaired by the bilateral icv A␤ 25-35 injections, while bilateral microinjections of the same dose of A␤ 35-25 was ineffective in affecting the long-term synaptic modification evoked by associative activation of cholinergic and GABAergic inputs, the cholinergic intracellular , or producing memory impairments. Thus restoring the synaptic plasticity involved in this associative activation of cholinergic and GABAergic inputs may offer an important therapeutic target in the treatment of early A␤-induced memory decline.
doi:10.1152/jn.00230.2001 pmid:11976381 fatcat:fszat4en2zfxphmrs4ftsn3fs4