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Differential effects and rates of normal aging in cerebellum and hippocampus.

ABSTRACT: Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4, 8, 12, 18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18- and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4- to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.

SUBMITTER: Woodruff-Pak DS

PROVIDER: S-EPMC2824421 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Differential effects and rates of normal aging in cerebellum and hippocampus.

Woodruff-Pak Diana S DS Foy Michael R MR Akopian Garnik G GG Lee Ka Hung KH Zach Jordan J Nguyen Kim Phuong Thi KP Comalli David M DM Kennard John A JA Agelan Alexis A Thompson Richard F RF

Proceedings of the National Academy of Sciences of the United States of America 20100108 4

Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorall ...[more]

PMID: 20080589

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Project description:Older adults show higher dual task performance decrements than younger adults. While this is assumed to be related to attentional capacity reductions, the precise affected functions are not specified. Such specification is, however, possible based on the "theory of visual attention" (TVA) which allows for modeling of distinct attentional capacity parameters. Furthermore, it is unclear whether older adults show qualitatively different attentional effects or whether they show the same effects as younger adults experience under more challenging conditions. By varying the complexity of the secondary task, it is possible to address this question. In our study, participants performed a verbal whole report of briefly presented letter arrays. TVA-based fitting of report performance delivered parameters of visual threshold t0, processing speed C, and visual short-term memory (VSTM) storage capacity K. Furthermore, participants performed a concurrent motor task consisting of continuous tapping of a (simple or complex) sequence. Both TVA and tapping tasks were performed under single and dual task conditions. Two groups of 30 younger adults each performed either the simple or complex tapping, and a group of 30 older adults performed the simple tapping condition. In older participants, VSTM storage capacity declined under dual task conditions. While no such effect was found in younger subjects performing the simple tapping sequence under dual task conditions, the younger group performing the complex tapping task under dual task conditions also showed a significant VSTM capacity reduction. Generally, no significant effect on other TVA parameters or on tapping accuracy was found. Comparable goodness-of-fit measures were obtained for the TVA modeling data in single and dual tasks, indicating that tasks were executed in a qualitatively similar, continuous manner, although quantitatively less efficiently under dual- compared to single-task conditions. Taken together, our results show that the age-specific effects of motor-cognitive dual task interference are reflected by a stronger decline of VSTM storage capacity. They support an interpretation of VSTM as central attentional capacity, which is shared across visual uptake and concurrent motor performance. Capacity limits are reached earlier, and already under lower motor task complexity, in older compared to younger adults.

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Differential effects and rates of normal aging in cerebellum and hippocampus.

Publications

Differential effects and rates of normal aging in cerebellum and hippocampus.

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