RT Journal Article
SR Electronic
T1 Elevated Postsynaptic [Ca<sup>2+</sup>]<sub>i</sub>and L-Type Calcium Channel Activity in Aged Hippocampal Neurons: Relationship to Impaired  Synaptic Plasticity
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9744
OP 9756
DO 10.1523/JNEUROSCI.21-24-09744.2001
VO 21
IS 24
A1 Olivier Thibault
A1 Robert Hadley
A1 Philip W. Landfield
YR 2001
UL http://www.jneurosci.org/content/21/24/9744.abstract
AB Considerable evidence supports a Ca2+dysregulation hypothesis of brain aging and Alzheimer's disease. However, it is still not known whether (1) intracellular [Ca2+]i is altered in aged brain neurons during synaptically activated neuronal activity; (2) altered [Ca2+]i is directly correlated with impaired neuronal plasticity; or (3) the previously observed age-related increase in L-type voltage-sensitive Ca2+ channel (L-VSCC) density in hippocampal neurons is sufficient to impair synaptic plasticity. Here, we used confocal microscopy to image [Ca2+]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 [Ca2+]i did not differ clearly with age. Greater elevation of somatic [Ca2+]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 [Ca2+]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 Ca2+ 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.