Adult hippocampal neurogenesis and memory interference

Abstract

Rats, subjected to low-dose irradiation that suppressed hippocampal neurogenesis, or a sham treatment, were administered a visual discrimination task under conditions of high, or low interference. Half of the rats engaged in running activity and the other half did not. In the non-runners, there was no effect of irradiation on learning, or remembering the discrimination response under low interference, but irradiation treatment increased their susceptibility to interference, resulting in loss of memory for the previously learned discrimination. Irradiated rats that engaged in running activity exhibited increased neuronal growth and protection from memory impairment. The results, which show that hippocampal cells generated in adulthood play a role in differentiating between conflicting, context-dependent memories, provide further evidence of the importance of neurogenesis in hippocampus-sensitive memory tasks. The results are consistent with computational models of hippocampal function that specify a central role for neurogenesis in the modulation of interfering influences during learning and memory.

Introduction

It is well established that new neurons, generated in the dentate gyrus during adulthood, are functionally integrated into existing hippocampal circuitry [1]. The reduction of adult neurogenesis, as seen following treatment with low-dose irradiation, anti-mitotic drugs, or in genetic mutations is associated with impaired performance on tests of hippocampus-dependent learning and memory [2], [3], [4], [5], [6], [7]. Conversely, factors that promote neurogenesis (e.g., physical activity, enriched environments) contribute to improved performance on hippocampus-dependent tasks [8], [9]. Notwithstanding these advances, the precise role of new cell growth in normal hippocampal function is unresolved.

The hippocampus is involved in the formation of flexible, contextually rich memories and there is compelling evidence that discrete neuronal representations within the dentate gyrus form the basis of these memories [10]. An important feature of hippocampus-based memories is that, by virtue of their distinctiveness and contextual richness, they are readily distinguished from other memories. When the hippocampus is impaired, memories become more schematic [11], susceptible to interfering influences [12], and, as a result, subject to inaccuracy.

We have proposed that neurogenesis provides a mechanism for hippocampal plasticity that is critical to the process of representing distinct memories [[3], [13]; see also Refs. [7], [14]]. It follows that, as part of this process, newly generated cells should also play a role in modulating interfering influences and minimizing the effect of competing memories during selective recall. This view is supported by recently developed computational models [e.g., Refs. [15], [16], [17]] which, while differing from one another in several respects, make the common prediction that adult-born hippocampal cells are essential to the process of reducing the adverse effects of interference during learning and memory.

As a direct test of this hypothesis, we used irradiation to suppress neurogenesis in adult rats, and tested them in a novel task that assessed memory for a learned discrimination response under conditions of high and low interference. In addition, half of the rats engaged in running activity, and the other half did not. It is well known that physical exercise can promote new cell growth and improve cognitive function in normal animals [9], [18]. We sought to determine if such effects were possible when hippocampal neurogenesis was compromised by irradiation.