Potential adaptive function for altered long-term potentiation mechanisms in aging hippocampus.
Age-dependent alterations in the induction of long-term potentiation (LTP) are well documented, providing a likely neural basis for memory decline associated with aging. Studies of neural plasticity are also important to understand the neural basis of individual differences in aging, ranging from significant cognitive impairment to preservation of function on a par with younger adults. To examine the cellular mechanisms that distinguish such outcomes, we studied the induction of LTP in male outbred young and aged rats behaviorally characterized in hippocampal-dependent spatial learning. We evaluated, in vitro, the magnitude of NMDA receptor (NMDAR)-dependent and -independent forms of LTP induced in the Schaffer collateral to CA1 synapses. We found that age substantially reduces NMDAR-dependent LTP across the spectrum of cognitive outcomes, whereas increased NMDAR-independent LTP occurs distinctively in high-performing aged rats. Moreover, in young rats, behavioral performance correlates strongly with the magnitude of NMDAR-LTP, whereas NMDAR-independent LTP correlates with behavioral performance only in aged rats. Together with similar previous findings on the mechanisms for LTD in this model, these results support the notion that a shift from NMDAR-dependent to NMDAR-independent mechanisms for neural plasticity during aging is associated with better cognitive outcomes.
Boric
Katica
K
Mind/Brain Institute and Department of Neurosciences, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Muñoz
Pablo
P
Gallagher
Michela
M
Kirkwood
Alfredo
A
D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology* / Q000523:psychology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013550:Swimming
D020746:Calcium Channels, L-Type; D016194:Receptors, N-Methyl-D-Aspartate