Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat.

Abstract

Neurophysiological and behavioral measures were obtained from 32 senescent (28-34 mo) and 32 mature adult (10-16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. After three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process. 1 The term "senescent" refers to an organism near its average maximum expected life span. If, for instance, dementia or other pathology is associated with the old organism, it is specified.

Aging impairs the late phase of long‐term potentiation at the medial perforant path‐CA3 synapse in awake rats

“…Our results are consistent with data obtained from studies performed in the aged rabbit (Solomon and Pendlebury, 1992) and rat DG under similar experimental conditions (Barnes, 1979;De Toledo-Morrell and Morrell, 1985) and suggest that aging affects NMDA receptordependent LTP maintenance at different hippocampal synapses in a homogeneous fashion. Given that previous studies have reported impaired DG LTP duration in aged rats (Barnes, 1979) and that the CA3 region receives MPP inputs from the same layer II stellate cells in the entorhinal cortex that project to the DG (Tamamaki and Nojyo, 1993), it may be that the agerelated deficits in LTP duration in the DG and area CA3 share common mechanisms. Reduced CA3 neuron number is unlikely to play a role in the impaired MPP-CA3 LTP duration observed here in aged rats because recent evidence indicates that neuron density in the CA3 pyramidal cell layer remains constant in aged rats (Poe et al, 2001).…”

“…As is the case at the MPP-DG synapse (Bramham et al, 1991), LTP induction at the MPP-CA3 synapse is dependent on NMDA receptor activation current data). Consistent with data obtained in the aged rat DG (Barnes, 1979) and area CA1 (Barnes et al, 1996), our finding that the same magnitude of MPP-CA3 LTP can be induced in aged rats as in young rats after the same number of identical high-frequency stimulation sessions suggests that NMDA receptor-mediated processes are intact in aged rats at this synapse. This observation does not exclude the possibility that individual NMDA receptor-mediated MPP-CA3 synaptic responses are reduced in aged rats, as is the case at the MPP-DG synapse .…”

“…In addition, recent observations indicate that selective perforant path-CA3 lesions impair memory recall (Lee and Kesner, in press). Importantly, because impaired recall appears to be characteristic of memory deficits in aged animals (Barnes, 1979;Foster et al, 1991), and because memory-impaired, aged animals show a loss of perforant path inputs to area CA3 (Smith et al, 2000), the present findings are consistent with the view that compromised function and plasticity in perforant path-CA3 projections likely underlie some of the memory deficits observed in aged animials.…”

“…We verified the accuracy of electrode placements by stereo-taxic coordinates and electrophysiological criteria in all rats (McNaughton and Barnes, 1977) and by histological examination in 10% of the animals. Electrodes were permanently implanted as previously described (Barnes, 1979). Briefly, electrodes were attached to gold Amphenol pins, mounted in 9-pin Malino/MacIntyre sockets (Ginder Scientific, Canada), and affixed to the skull with dental acrylic.…”

“…Studies document accelerated DG LTP decay in aged rodents (Barnes, 1979) and rabbits (Solomon and Pendlebury, 1992). However, all published studies of age-related deficits in LTP in the hippocampal formation have been done in the MPP-DG or in the Schaffer-collateral-CA1 synapse (Barnes et al, 1996).…”