Aging has a profound impact on learning and encoding new memories. Advances in the field of aging suggest that changes at the cellular level rather than structural alterations are more relevant for understanding cognitive deficits associated with aging. In this regard, electrophysiological analysis of synaptic function in the CA1 region of the hippocampus has provided the important insights that age disrupts the mechanisms by which the synaptic connectivity is modified to encode new memories. These changes in synaptic plasticity provide a conceptual basis to understand learning deficits in aged individuals. Although focusing on alterations in CA1 associated with learning deficits has been fruitful, recently it has become clear the need to expand the research scope. First is the realization that other circuits in the hippocampus participate differently during memory encoding, and that aging affects them differently, and even more prominently, in the case of CA3. In addition, although on average cognitive abilities decline with age, a recognizable subpopulation of aged individuals maintains mental abilities. Thus, while an ultimate goal could be to preserve the integrity of the cellular processes normally affected by age, a complementary approach is to focus on adaptative changes occuring naturally in response to lost functions. We approach these issues ex vivo, by studying synaptic plasticity in hippocampal slices from aged rats characterized in a hippocampal- dependent learning task. The goals of this project are to 1) understand how aging affects the synaptic functions that support learning in CA3, 2) identify mechanisms that allow some aged individuals to maintain cognitive abilities and 3) understand how intervention treatments that improve learning in aged individuals affect synaptic plasticity. Our research suggests that some mechanisms of synaptic plasticity are irreversibly lost in aged rats. However, those aged individuals that maintained cognitive performance manage to compensate for the lost by boosting other mechanisms. These adaptatively enhanced plasticity mechanisms are an obvious target for therapeutical strategies aimed at restoring learning in aged individuals.
Aging can have a pronounced impact on mental abilities, particularly on learning and memory. Although such decline is widespread enough to be often considered a normal aspect of aging, some older individuals retain strong cognitive abilities. This proposal will investigate the type of neural adaptive changes that are required to maintain cognitive performance at old age.
|Wang, Hui; Ardiles, Alvaro O; Yang, Sunggu et al. (2016) Metabotropic Glutamate Receptors Induce a Form of LTP Controlled by Translation and Arc Signaling in the Hippocampus. J Neurosci 36:1723-9|
|Megill, Andrea; Tran, Trinh; Eldred, Kiara et al. (2015) Defective Age-Dependent Metaplasticity in a Mouse Model of Alzheimer's Disease. J Neurosci 35:11346-57|
|Huang, Shiyong; Rozas, Carlos; Treviño, Mario et al. (2014) Associative Hebbian synaptic plasticity in primate visual cortex. J Neurosci 34:7575-9|
|Wang, Hui; Megill, Andrea; Wong, Philip C et al. (2014) Postsynaptic target specific synaptic dysfunctions in the CA3 area of BACE1 knockout mice. PLoS One 9:e92279|
|Megill, Andrea; Lee, Taehee; DiBattista, Amanda Marie et al. (2013) A tetra(ethylene glycol) derivative of benzothiazole aniline enhances Ras-mediated spinogenesis. J Neurosci 33:9306-18|
|Ardiles, Alvaro O; Ewer, John; Acosta, Monica L et al. (2013) Octodon degus (Molina 1782): a model in comparative biology and biomedicine. Cold Spring Harb Protoc 2013:312-8|
|Yang, Sunggu; Megill, Andrea; Ardiles, Alvaro O et al. (2013) Integrity of mGluR-LTD in the associative/commissural inputs to CA3 correlates with successful aging in rats. J Neurosci 33:12670-8|
|Ardiles, Alvaro O; Tapia-Rojas, Cheril C; Mandal, Madhuchhanda et al. (2012) Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease. Proc Natl Acad Sci U S A 109:13835-40|
|LeGates, Tara A; Altimus, Cara M; Wang, Hui et al. (2012) Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491:594-8|
|Wang, Hui; Megill, Andrea; He, Kaiwen et al. (2012) Consequences of inhibiting amyloid precursor protein processing enzymes on synaptic function and plasticity. Neural Plast 2012:272374|
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