Age-Associated Alterations of Hippocampal Place Cells Are Subregion Specific

Abstract

Aging is associated with spatial memory impairments and with deficient encoding of information by the hippocampus. In young adult rats, recent studies on the firing properties of hippocampal neurons have emphasized the importance of the CA3 subregion in the rapid encoding of new spatial information. Here, we compared the spatial firing patterns of CA1 and CA3 neurons in aged memory-impaired rats with those of young rats as they explored familiar and novel environments. We found that CA1 place cells in aged and young rats had similar firing characteristics in the familiar and novel environments. In contrast, aged CA3 place cells had higher firing rates in general and failed to change their firing rates and place fields as much as CA3 cells of young rats when the rats were introduced to a novel environment. Thus, aged CA3 cells failed to rapidly encode new spatial information compared with young CA3 cells. These data suggest an important and selective contribution of CA3 dysfunction to age-related memory impairment.

Neurocognitive aging: prior memories hinder new hippocampal encoding

“…Furthermore, the extent of the 'rigidity' of place cells in old rats predicts the magnitude of spatial memory impairment [80]. Remarkably, rigid hippocampal representations occur almost exclusively in the CA3 subregion and not among CA1 cells [82]. These observations parallel the impairments that arise with proactive interference in aged humans, suggesting that the aged hippocampus fails to encode appropriate new contextual information owing to proactive interference from prior related experiences.…”

“…As revealed in place-cell recordings, in young rats a relatively modest change in environment or in task demands is sufficient to induce the switch from recalling a stored representation of the familiar environment to creating a new representation for the changed environment [83,84]. By contrast in aged rats, CA3 place-cell recordings indicate a propensity to recall stored representations rather than create new ones [82]. Several factors affecting the DG and CA3 in the aged brain are consistent with a condition in which the balance between the processes of pattern separation and pattern completion is altered, and these alterations, in addition to other intrinsic changes, also alter CA1 function.…”

“…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).…”

“…Thus, in aged animals, decreased cholinergic input might reduce the relative influence of new information through the perforant path, and subsequently favor the reactivation of stored information in the CA3 auto-associative network [50,51]. Reduced ACh-mediated modulation, in combination with fewer external details arriving at the reduced number of entorhinal synapses, might therefore bias the aged CA3 subregion towards maintenance of the original representation, and this is exemplified by rigidity of CA3 place cells [82]. Owing to the combined effects of aging in this sector of the hippocampus (i.e.…”