Region‐specific age effects on AMPA sensitivity: Electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1

Abstract

The effects of aging on the responsiveness of hippocampal neurons to iontophoretic application of L-glutamate and AMPA were studied in vitro. There were no effects of age on neuronal responses to L-glutamate; however, CA1 pyramidal cells of old rats, but not granule cells in the fascia dentata, showed both a smaller reduction in extracellularly-recorded synaptic responses following application of AMPA (presumably mediated by depolarization), and smaller extracellular "DC" fields (measured by subtracting the DC potentials at the dendrite and soma following AMPA application in the dendrites). To examine the cellular bases of this age-related alteration in AMPA sensitivity, two additional electrophysiological approaches were used: (1) measurement of the amplitude ratios of extracellular EPSP and fiber potential components of the Schaffer collateral-CA1 response; (2) measurement of intracellularly recorded unitary EPSPs and quantal analysis of their fluctuations. The interpretations that would be placed on four hypothetical possible outcomes of such experiments are outlined and assessed in relation to the experimental data. The pattern of results obtained in the present experiments supports the following conclusions: In old rats, individual Schaffer collateral synapses do not appear to have altered AMPA receptor properties, as neither the mean size of the unitary synaptic response nor the apparent quantal size differs between age groups; however, the data do support the conclusion that there are fewer synapses per Schaffer collateral branch in old versus young CA1 pyramidal cells.

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

“…In fact, age-related impairments in CA1 LTP are generally obscured by high-frequency stimulation but are revealed when weaker, near-threshold stimulus protocols are applied (Deupree et al, 1993;Moore et al, 1993;Norris et al, 1996). These data collectively support the conclusion that fewer functional excitatory CA1 synapses exist in aged rats (Barnes et al, 1992(Barnes et al, , 1997, although it is not known whether this synapse loss covaries with learning ability.…”

Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca2+Channels

“…By facilitating and inhibiting LTD and LTP induction, respectively, the overall effect of increased L-channel activity during aging would favor the weakening of synaptic efficacy , which is a primary electrophysiological marker for age-related cognitive deficits (Barnes et al, 1992(Barnes et al, , 1996. Thus, the current study provides a plausible mechanistic link between age-related memory deficits and L-channel activity in the aging brain (Deyo et al, 1989;Straube et al, 1990;Levere and Walker, 1992;Ingram et al, 1994;Kowalska and Disterhoft, 1994;Soloman et al, 1995;Thibault and Landfield, 1996).…”

The Effect of Aging on Experience-Dependent Plasticity of Hippocampal Place Cells

“…The LTP deficit explanation is made more plausible by recent in vitro findings on age-related deficits of LTP induction (Deupree et al, 1991(Deupree et al, , 1993Moore et al, 1993) and new evidence suggesting that such an LTP induction failure in old rats may result from a reduction in the net synaptic input in old pyramidal cells . The latter effect may partly be a consequence of a reduced number of f unctional synaptic contacts made by a given CA3 pyramidal cell axon (Barnes et al, 1992;Barnes, 1994) or reduced temporal summation in old hippocampal cells (Rosenzweig et al, 1997). Another possibility may be the reduction in frequency potentiation that occurs in old rats during LTPinducing forms of stimulation (Landfield, 1988), which would also lead to a reduction in net dopolarization.…”