ArticlesAge-Related Decrease in the N-Methyl-d-AspartateR-Mediated Excitatory Postsynaptic Potential in Hippocampal Region CA1
Section snippets
Method
Three age groups of F-344 male rats (n = 10, 1 month; 10, 9 months; 14, 26 months) were behaviorally tested between 3–14 days before the conduct of the electrophysiological experiments. The 1-month rats were obtained from Charles River Laboratories (Wilmington, MA), and the 9- and 26-month rats were retired breeders obtained from the National Institute on Aging (NIA) colony at Harlan Sprague-Dawley, Indianapolis, IN. On arrival, the rats were singly housed in Plexiglas guinea pig tubs with free
Acquisition and retention of the spatial version of the Morris swim task.
Four old animals exhibited severe impairment on the visible platform task (latency to the visible platform >20 s), due to thigmotaxis, apparent inability to see the platform, or inability to swim. These rats were excluded from the behavioral and electrophysiological analyses. Data from the spatial and cued versions of the Morris swim task were analyzed for 10 animals in each age group.
The total distance of the path taken between release in the pool and escape onto the hidden platform, for each
Discussion
The principal new finding of our experiment is the observation of an equivalent age-related decline in the NMDAR and non-NMDAR-mediated EPSPs for a given fiber potential amplitude in CA1. This finding is consistent with the conclusion that, during aging, there is a reduction in the number of Schaffer collateral synapses, with no change in either the relative or absolute amplitudes of NMDAR- or non-NMDAR-mediated synaptic responses at individual remaining synapses. If there are, in fact, fewer
Acknowledgements
We thank B. L. McNaughton for helpful discussions in the planning stages of this work, and constructive suggestions for the preparation of these data for publication.
References (59)
Normal agingRegionally specific changes in hippocampal synaptic transmission
Trends Neurosci.
(1994)- et al.
NMDA depolarizations and long-term potentiation are reduced in the aged rat neocortex
Brain Res.
(1990) - et al.
Increased [3H] glutamate binding in aged rats
Brain Res.
(1981) - et al.
CNQX blocks acidic amino acid induced depolarizations and synaptic components mediated by non-NMDA receptors in rat hippocampal slices
Neurosci. Lett.
(1988) - et al.
Decreased density, but not number, of N-methyl-d-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats
Brain Res.
(1990) - et al.
A cluster analysis study of acetyl-l-carnitine effect on NMDA receptors in aging
Exp. Gerontol.
(1993) - et al.
Aging reduces neostriatal responsiveness to N-methyl-d-aspartate and dopamine—an in vitro electrophysiological study
Neuroscience
(1996) - et al.
Acetyl-l-carnitineBehavioral, electrophysiological, and neurochemical effects
Neurobiol. Aging
(1993) - et al.
Age-related alterations in potentiation in the CA1 region in F344 rats
Neurobiol. Aging
(1993) - et al.
Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats
Brain Res.
(1991)
Increase in perforant path quantal size in aged F-344 rats
Neurobiol. Aging
Hippocampal markers of age-related memory dysfunctionbehavioral, electrophysiological and morphological perspectives
Prog. Neurobiol.
N-methyl-d-aspartate mediated responses decrease with age in Fischer 344 rat brain
Neurobiol. Aging
Excitatory amino acids and Alzheimer’s disease
Neurobiol. Aging
A simple perfusion chamber for the study of nervous tissue slices in vitro
J. Neurosci. Methods
A selective N-methyl-d-aspartate antagonist depresses epileptiform activity in rat hippocampal slices
Neurosci. Lett.
Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices
Neuron
Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats
Brain Res.
Effects of aging and chronic nimodipine on hippocampal binding of [3H]CGS 19755
Neurobiol. Aging
Impaired synaptic potentiation process in the hippocampus of aged, memory deficient rats
Brain Res.
Relationship between performance in the Morris water task, visual acuity, and thermoregulatory function in aged Fischer-344 rats
Behav. Brain Res.
Synaptic enhancement in fascia dentatacooperativity among coactive afferents
Brain Res.
Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the hippocampus in vitro
Neurosci. Lett.
Age-related decreases of the NMDA receptor-mediated noradrenaline release in rat hippocampus and partial restoration by d-cycloserine
Euro. J. Pharmacol.
Effects of age on l-glutamate-induced depolarization in three hippocampal subfields
Neurobiol. Aging
Age-related decrease in cholinergic synaptic transmission in three hippocampal subfields
Neurobiol. Aging
Presynaptic actions of glutamate receptor agonists in the CA1 region of rat hippocampus in vitro
Eur. J. Pharmacol.
Age-related decreases of the N-methyl-D-aspartate receptor complex in the rat cerebral cortex and hippocampus
Brain Res.
Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys
Neurobiol. Aging
Cited by (127)
Advanced age has dissociable effects on hippocampal CA1 ripples and CA3 high frequency events in male rats
2022, Neurobiology of AgingTargeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder
2021, Acta Pharmaceutica Sinica BCitation Excerpt :NMDAR plays an essential role in the induction of LTP and the acquisition of memories. The hypofunction of NMDAR is primarily responsible for deficits in synaptic plasticity in aged animals, animal models, and patients with age-related neurodegenerative diseases and other cognitive disorders7,8,49–52. Recent studies have identified alterations in the functional properties of NMDAR, rather than in the level of expression or density, as the cause of NMDAR hypofunction in individuals with various disorders49,50,53,54.
Senescent neurophysiology: Ca<sup>2+</sup> signaling from the membrane to the nucleus
2019, Neurobiology of Learning and MemoryCellular calcium signaling in the aging brain
2019, Journal of Chemical NeuroanatomyCitation Excerpt :Age-associated decline in NMDAR function is observed mainly in CA1-CA3 regions of hippocampus and in prefrontal cortex, the brain regions mainly involved in learning and memory, in aged animals. This may contribute to cognitive impairment in elderly population (Barnes et al., 1997; Eckles-Smith et al., 2000; Liu et al., 2008; Magnusson, 1998; Zhao et al., 2009). Functional decline in NMDARs with age can be attributed to the following factors:
Proteome profiling in the hippocampus, medial prefrontal cortex, and striatum of aging rat
2018, Experimental Gerontology