Cognitive Aging and the Hippocampus: How Old Rats Represent New Environments

Abstract

Spatial learning impairment in aged rats is associated with changes in hippocampal connectivity and plasticity. Several studies have explored the age-related deficit in spatial information processing by recording the location-specific activity of hippocampal neurons (place cells). However, these studies have generated disparate characterizations of place cells in aged rats as unstable ( . To reconcile these findings, we recorded place cells from aged and young rats as they repeatedly explored both a highly familiar environment and an initially novel environment, and we repeatedly tested whether the place fields formed in the novel environment were anchored by external cues. Initially, spatial representations in aged rats were abnormally maintained between the familiar and novel environments. Then, new representations were formed but were also delayed in becoming anchored to the external landmarks. Finally, even when the new spatial representations became bound to the landmarks, they were multi-stable across repetitive exposures to the formerly novel environment. These observations help to reconcile previously divergent characterizations of spatial representation in aged rats and suggest a model of cognitive aging and hippocampal function.

Neurocognitive aging: prior memories hinder new hippocampal encoding

“…With similar inconsistency, spatial representations in aged rats rotate with rotated landmarks on some occasions but not others [81]. Furthermore, rigidity can be evident in the encoding properties of CA1 cells [78][79][80][81], but this is not as invariable in CA1 as it seems to be in CA3 [82]. As we now describe further, in our model these inconsistencies in CA1 might represent shifts between dependence on CA3 inputs and direct EC inputs to the CA1 subregion.…”

“…Of particular importance here, numerous studies have shown that CA3 and CA1 place cells of aged rats fail to encode new spatial or task information rapidly [78][79][80][81][82]. After young rats have explored one environment until it becomes highly familiar, introduction into a novel environment typically results in the creation of a new spatial representation, reflected in spatial firing patterns of hippocampal neurons that are drastically different from those associated with the familiar environment [83,84].…”

“…Reduced inputs might not transmit sufficient details to resolve changes in external contextual information that would normally be used to induce a switch from pattern completion to pattern separation. Based on this, the rigidity of encoding observed downstream in CA3 place cells [78][79][80][81][82] might be due, at least in part, to failure in the DG to reduce the similarity of input patterns sufficiently (e.g. pattern separation).…”

“…The inconsistencies in CA1 encoding are perhaps best exemplified by the fluctuations between multiple stable representations observed when aged rats are returned repeatedly to the same environment after intervening experience [85]. With similar inconsistency, spatial representations in aged rats rotate with rotated landmarks on some occasions but not others [81]. Furthermore, rigidity can be evident in the encoding properties of CA1 cells [78][79][80][81], but this is not as invariable in CA1 as it seems to be in CA3 [82].…”

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

“…Declarative memory (memory for people, facts, and events, as well as for spatial locations) is dependent upon the medial temporal lobe system, including the hippocampal formation [11,15,39,44]. Dysfunction of this system and concomitant loss of associated learning and memory functions are well-documented at advanced ages.…”