Learning Enhances the Survival of New Neurons beyond the Time when the Hippocampus Is Required for Memory

Abstract

Trace memories are formed when a stimulus event becomes associated with another event that occurs later in time and is discontinuous with the first event. The formation of trace memories enhances the survival of newly generated neurons in the dentate gyrus of the adult hippocampus (Gould et al., 1999a). Here we tested whether the acquisition of trace memories early during training is sufficient to enhance cell survival. We also examined whether the new neurons affected by trace memory formation persist indefinitely or only as long as the hippocampus is necessary for the expression of those memories. Groups of adult rats were injected with bromodeoxyuridine (BrdU), a marker of dividing cells, and trained 1 week later with paired stimuli using a trace eyeblink conditioning task or exposed to the same number of unpaired stimuli. Cell survival was assessed after different numbers of training trials and survival periods after training. Overall cell survival was not enhanced by exposure to 200 trials of paired stimuli during trace conditioning. However, there was a positive correlation between performance of individual animals and cell survival. In addition, exposure to 800 trials of paired stimuli during trace conditioning increased the number of BrdU-labeled cells 60 d after training. The vast majority of these cells were neurons and coexpressed the neuronal markers class III ␤-tubulin or neuronal nuclei. These data suggest that individual differences in associative learning predict whether new neurons will survive and that once affected, these neurons remain for months and beyond the time when they are required for the retention of trace memories.

Neurogenesis and Helplessness Are Mediated by Controllability in Males But Not in Females

“…Three weeks after the BrdU injection, 71% of the cells (n= 4; >10 cells per rat) were labeled with both BrdU and NeuN (Figure 2). Thus, the majority of cells did differentiate into neurons and the percentage is consistent with those reported in our previous studies (Gould, Beylin, Tanapat, Reeves, and Shors 1999) (Leuner, Mendolia-Loffredo, Kozorovitskiy, Samburg, Gould, and Shors 2004). Since the effect of stress was to prevent the production of new cells, the NeuN data simply indicate the percentage of new cells that would have expressed neuronal markers, if they had survived.…”

Is there a link between adult neurogenesis and learning?

“…However, this relationship does not extend itself to training with all types of tasks. With trace eyeblink conditioning, exposure to just 200 trials of training did not enhance cell survival, whereas training with 800 trials did (Leuner et al, 2004c). It is important to note that even though the overall number of newborn cells was not affected by a shorter training episode, the number of learned responses emitted during the 200 trials of training was positively correlated with the number of cells that survived.…”

“…However, this is not necessarily the case. It has been reported that learning increases the survival of new neurons in the hippocampus and they remain there for at least two months after training (Leuner et al, 2004c), which is well beyond the time when the hippocampus is required for the retention of those memories (Kim et al, 1995;Takehara et al, 2003). These findings do not exclude the possibility that new neurons participate transiently in memory storage but rather, that if that is their role, eventually they may outlive their usefulness, perhaps becoming important for some other function.…”

“…However, the direction of the effect is not always the same. For example, it has been shown that training with trace eyeblink conditioning, spatial learning in the Morris water maze and conditioned food preference increase the number of newborn cells in the DG of adult rats (Gould et al, 1999c;Ambrogini et al, 2000;Lemaire et al, 2000;Dobrossy et al, 2003;Leuner et al, 2004c;Hairston et al, 2005;Olariu et al, 2005). These effects appear to be specific to learning that requires the hippocampus.…”

Hippocampal Granule Neuron Number and Dentate Gyrus Volume in Antidepressant-Treated and Untreated Major Depression

“…Hippocampal-dependent learning increases the survival of maturing DG cells (Leuner et al, 2004) and both environmental enrichment and physical exercise increase DG neurogenesis in animal studies (Nilsson et al, 1999;van Praag et al, 1999). Activity improves the survival rate of new DG neurons (Deisseroth et al, 2004).…”