Differential effects and rates of normal aging in cerebellum and hippocampus
| Autor: | Garnik G. Akopian, Ka Hung Lee, Alexis Agelan, Kim Phuong Thi Nguyen, Diana S. Woodruff-Pak, Michael R. Foy, Jordan Zach, John A. Kennard, Richard F. Thompson, David M. Comalli |
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| Rok vydání: | 2010 |
| Předmět: |
Aging
Cerebellum Long-Term Potentiation Hippocampus Hippocampal formation Mice medicine Animals Learning Fear conditioning Multidisciplinary Behavior Animal Long-Term Synaptic Depression Classical conditioning Long-term potentiation Biological Sciences Electrophysiological Phenomena Mice Inbred C57BL medicine.anatomical_structure nervous system Eyeblink conditioning Cerebellar cortex Psychology Neuroscience |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:1624-1629 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0914207107 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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