Neurogenesis, learning and associative strength

Abstract

Though the role of the hippocampus in processes of learning and memory is well established, the role of new neurons generated there is less understood. Training on some associative learning tasks increases the likelihood that new cells in the subgranular zone of the dentate gyrus will survive. In the rat, an effective training procedure is trace eyeblink conditioning, in which a conditioned stimulus (CS) is paired with an aversive stimulation to the eyelid (unconditioned stimulus; US), but the stimuli are separated by a temporal gap. Here, we manipulated the asymptote or rate of acquisition during trace conditioning, and examined survival of cells generated 1 week before training. Acquisition was disrupted by decreasing associative strength by insertion of unpredicted USs or slowed with latent inhibition. The number of cells was increased in animals that were trained with trace conditioning, irrespective of the decrease in associative strength or slowed acquisition. Disrupting acquisition with unsignaled USs still increased cell numbers, suggesting that the learning effect on cell survival is not dependent on reliable expression of the conditioned response. Further, animals in the latent inhibition conditions that learned but required more trials also retained more of the new cells than animals requiring fewer trials. The number of cells that survived after the effective training procedures was similar to the number of cells that were available for rescue at the beginning of training. Thus, learning can rescue the majority of cells expressed at the beginning of training, and does so most effectively when acquisition requires many trials.

Fig. 1

(A) Experimental timeline. (B) Behavioral results from animals trained with only predicted USs (Predicted) and animals trained with the addition of Unpredicted USs. Data are presented as a mean ± SEM percentage of conditioned responses with the first 100 trials presented in 20-trial blocks, with the remaining 700 in 100-trial blocks. (C) Bars represent the mean ± SEM number of BrdU-labeled cells in the SGZ and GCL of the dentate gyrus of naïve animals and groups Predicted and Unpredicted. *P < 0.05, denotes groups which differ from Naïve controls.

Fig. 2

(A) Experimental timeline. (B) Behavioral results from animals trained with the Delay procedure. (C) Behavioral results from animals trained with the Trace procedure. Data are presented as a mean ± SEM percentage of conditioned responses with the first 100 trials presented in 20-trial blocks with the remaining 700 trials in 100-trial blocks. (D) Bars represent the mean ± SEM number of BrdU-labeled cells in the SGZ and GCL of the dentate gyrus of naïve animals and groups Delay, LI Delay, Trace and LI Trace conditions. *P < 0.05, denotes groups which differ from naïve controls.

Fig. 3

BrdU-labeled cells in the dentate gyrus of the hippocampus from similar sections of an animal in the (A) 7-day naïve condition, (B) 12-day naïve condition, (C) Trace condition and (D) Delay condition.

Fig. 4

The majority of BrdU-labeled cells appear to differentiate into neurons. A representative cell from the dentate gyrus that expressed (A) DCX, (B) BrdU and (C) DCX is shown.

Fig. 5

(A) Bars represent the average number of trials required for each behavioral condition in Experiments 2 and 3 to reach 100 trials with 60% conditioned responses. (B) The number of trials required to reach behavioral criterion correlates with the number of BrdU-labeled cells expressed in the dentate gyrus.