Age‐Related Decrease in the Schaffer Collateral‐Evoked EPSP in Awake, Freely, Behaving Rats

Abstract

Synaptic response size in the CA1 region of the hippocampus in aged rats is reduced for a given stimulus intensity, compared with that elicited in young rats. Consistent with the in vitro findings of reduced Schaffer collateral-evoked CA1 EPSPs in old rats, the population currents evoked to iontophoretically applied AMPA are also smaller relative to the presynaptic fiber potential amplitude. On the other hand, the size of the presynaptic fiber potential and amplitude of unitary intra-cellularly recorded EPSP responses do not change across age in the CA1 region. These electrophysiological findings are consistent with the hypothesis that old rats have fewer functional synaptic contacts per Schaffer collateral axon than do young rats. The possibility that this age change arises as a result of a differential tissue recovery response to in vitro preparation was examined in the present study. CA1 presynaptic fiber potential and EPSP amplitudes evoked by the stimulation of Schaffer collateral afferents were studied in intact, freely behaving young and old rats. We confirmed in vivo the pattern of electrophysiophysiological results previously reported in vitro and found significant correlations between the synaptic response amplitudes and the accuracy of spatial behavior in the Morris swim task. The data suggest that changes in functional connectivity of old rats may be a significant contributor to cognitive changes during aging.

Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice

“…This reduction in NonTg mice at 8 months is most likely due to a normal age related decline of synaptic AMPAR activity, possibly related to reduced postsynaptic AMPAR activity (Barnes, Rao, and Orr, 2000; Kumar and Foster, 2007). In the 8 month old 3xTg-AD mice, this age related decline in synaptic transmission may be exaggerated due to Aβ-induced AMPAR trafficking (Hsieh, Boehm, Sato, Iwatsubo, Tomita, Sisodia, and Malinow, 2006) or changes in calcium homeostasis (Chakroborty, Kim, Schneider, Jacobson, Molgo, and Stutzmann, 2012).…”

Amyloid Beta Inhibits Olfactory Bulb Activity and the Ability to Smell

“…For instance, we found that the network activity generated by the OB can be reduced by the application of 30 nM Aβ in slices taken from 3-week-old animals (Figure 3), whereas it was necessary to apply 100 nM Aβ to induce a similar reduction in network activity of hippocampal slices taken from 2-week-old animals [52]. Aging has been associated with loss of synaptic contacts [83,84], silencing of synapses [83-85], or a decrease of postsynaptic responsiveness [83,84,86,87] and synaptic dynamics [68, for review see 87], which is reflected in deficits in the generation of certain spontaneous oscillatory activities [52,88]. It remains to be determined which of these phenomena is responsible for the age dependency of Aβ-induced OB network dysfunction.…”

Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

“…Aging is associated with specific impairments of hippocampal function, which is reflected in learning and memory deficit [31,48]. These deficits could be associated with the loss of synaptic contacts [49], silencing of synapses [32,50] or decrease of postsynaptic responsiveness [51] (for review see [52]). This is reflected in deficits in the generation of long term plasticity [31,52,53] as well as alterations in the generation of certain spontaneous oscillatory activities [33].…”

“…Possibly by affecting cognitive-related processes such as long term plasticity [13][14][15][16][17][18], neuronal network oscillations [11,19,20] or neuronal codification [21]. Accordingly with this line of evidence, we have recently shown that acute application of high nanomolar concentrations of mostly monomeric forms of A [25][26][27][28][29][30][31][32][33][34][35] affects hippocampal network functioning from single cell to network level, both in vitro and in vivo [11]. However, those high concentrations have been observed rarely in the brain of AD patients [22][23][24][25][26].…”

“…Thus, our first aim was to test if an oligomerized solution of A (osA ) affects hippocampal spontaneous network activity at clinically relevant concentrations. There is evidence that neuronal network activity declines with age and that this alteration is reflected in reduction of synaptic transmission and changes in plasticity [31,32]. Moreover, gamma hippocampal oscillations decrease with age [33].…”