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• W1497413049 endingPage "9756" @default.
• W1497413049 startingPage "9744" @default.
• W1497413049 abstract "Considerable evidence supports a Ca 2+ dysregulation hypothesis of brain aging and Alzheimer's disease. However, it is still not known whether (1) intracellular [Ca 2+ ] i is altered in aged brain neurons during synaptically activated neuronal activity; (2) altered [Ca 2+ ] i is directly correlated with impaired neuronal plasticity; or (3) the previously observed age-related increase in L-type voltage-sensitive Ca 2+ channel (L-VSCC) density in hippocampal neurons is sufficient to impair synaptic plasticity. Here, we used confocal microscopy to image [Ca 2+ ] i in single CA1 neurons in hippocampal slices of young-adult and aged rats during repetitive synaptic activation. Simultaneously, we recorded intracellular EPSP frequency facilitation (FF), a form of short-term synaptic plasticity that is impaired with aging and inversely correlated with cognitive function. Resting [Ca 2+ ] i did not differ clearly with age. Greater elevation of somatic [Ca 2+ ] i and greater depression of FF developed in aged neurons during 20 sec trains of 7 Hz synaptic activation, but only if the activation triggered repetitive action potentials for several seconds. Elevated [Ca 2+ ] i and FF also were negatively correlated in individual aged neurons. In addition, the selective L-VSCC agonist Bay K8644 increased the afterhyperpolarization and mimicked the depressive effects of aging on FF in young-adult neurons. Thus, during physiologically relevant firing patterns in aging neurons, postsynaptic Ca 2+ elevation is closely associated with altered neuronal plasticity. Moreover, selectively increasing postsynaptic L-VSCC activity, as occurs in aging, negatively regulated a form of short-term plasticity that enhances synaptic throughput. Together, the results elucidate novel processes that may contribute to impaired cognitive function in aging." @default.
• W1497413049 created "2016-06-24" @default.
• W1497413049 creator A5005844055 @default.
• W1497413049 creator A5008963010 @default.
• W1497413049 creator A5043820510 @default.
• W1497413049 date "2001-12-15" @default.
• W1497413049 modified "2023-10-16" @default.
• W1497413049 title "Elevated Postsynaptic [Ca²⁺]_iand L-Type Calcium Channel Activity in Aged Hippocampal Neurons: Relationship to Impaired Synaptic Plasticity" @default.
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