Brain Aging: Changes in the Nature of Information Coding by the Hippocampus

Abstract

Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information. Key words: spatial learning; spatial memory; place field; electrophysiology; encoding; representation; rat; ageDiminished memory capacity is a well known concomitant of aging in humans (Craik, 1990;Rapp and Heindel, 1994) and animals (Barnes, , 1988DeToledo-Morrell et al., 1988;Gage et al., 1988;Rapp and Amaral, 1992;Rapp and Heindel, 1994;Gallagher et al., 1995). Across all species studies have found that the memory deficit associated with aging is characterized by large variability in cognitive capacities so that some aged subjects perform as well young subjects, whereas others show severe impairment (Markowska et al., 1989;Bachevalier et al., 1991;Rapp and Amaral, 1992;Gallagher et al., 1993). Many experiments have identified anatomical, molecular, and physiological markers of memory impairment in the hippocampal region of aged animals and humans (Barnes, 1979(Barnes, , 1988DeToledo-Morrell et al., 1988;Gage et al., 1988;Rapp and Amaral, 1992; Gallagher et al., 1994;Rapp and Heindel, 1994;Grady et al., 1995;Rapp and Gallagher, 1996), but few studies to date have characterized age-associated changes in the nature of information encoded by neurons in the brain.In rats aging results in an impairment in spatial learning and memory. Spatial learning in rats is strongly dependent on hippocampal function (Morris et al., 1982), and the firing patterns of hippocampal pyramidal cells correlate with the spatial location of an animal in the testing environment during exploratory behavior (O' Keefe and Nadel, 1978). The firing pattern of such hippocampal "place cells" is controlled by spatial and other relationships among multiple environmental cues and ongoing behavior and may reflect higher-order memory processing (O'Keefe and Nadel, 1978;Muller and Kubie, 1987;Eichenbaum, 1996).The activity of place cells in rats ex...

Brain Aging: Impaired Coding of Novel Environmental Cues

“…Aged rats are impaired in spatial learning, although the severity of the deficit is highly variable (Barnes, 1988(Barnes, , 1994DeToledo-Morrell et al, 1988;Gage et al, 1988;Markowska et al, 1989;Rapp and Amaral, 1992;Gallagher and Nicolle, 1993;Rapp and Heindel, 1994). Previous studies on place cells in aged rats have reported that their spatial specificity may decrease with age (Barnes et al, 1983), but other recent studies, including our own, have failed to confirm any clear association between place field specificity and impaired spatial learning in aged animals (Mizumori et al, 1996;Tanila et al, 1997). However, all of the electrophysiological studies were conducted using environments that were highly familiar to the animals, whereas virtually all the studies that demonstrate the age-related spatial impairment focus on learning new spatial environments.…”

“…Three young (4 -6 months, 35-450 gm at the beginning of the recordings) and four aged (25-29 months, 450 -600 gm) male Long-Evans rats served as subjects. Rats were the same that were used in the study described in our accompanying paper (Tanila et al, 1997). The animals were individually housed from the beginning of pretraining, maintained on a 12 hr light/dark cycle, and given ad libitum access to water.…”

“…The techniques are been described in detailed in our accompanying paper (Tanila et al, 1997) and are only briefly mentioned here. The recording electrodes were tetrodes made of 30 m Formvar-coated nichrome wires, and the stimulation electrodes were a twisted pair of 100 m Teflon-coated stainless steel wires.…”

The hippocampal debate: are we asking the right questions?

“…In addition, hippocampal cells show place field changes with changes in environments or the available constellation of cues [17,90,93,129,148,181,219,223,250]. Animals with learning deficits (whether by aging, NMDA-blockade, or cortical lesions) also show an instability of place fields across sessions, though not within the session itself [8,11,87,127,189,190,220,221].…”

Spatial reference and working memory across the lifespan of male Fischer 344 rats

“…Moreover, a variety of functional deficits in these structures and changes in neuronal encoding properties correlate with individual differences in spatial learning abilities [3,10,12,20,41]. However, it has been reported that minimal individual variability exists among aged male F344 rats and that variability within this and potentially other rodent models of human cognitive aging may be a result of within-subject factors rather than reliable individual differences between aged rats [3,18].…”