Training memory without aversion: Appetitive hole-board spatial learning increases adult hippocampal neurogenesis

Abstract

Learning experiences are potent modulators of adult hippocampal neurogenesis (AHN). However, the vast majority of findings on the learning-induced regulation of AHN derive from aversively-motivated tasks, mainly the water maze paradigm, in which stress is a confounding factor that affects the AHN outcome. Currently, little is known regarding the effect of appetitively-motivated training on AHN. Hence we studied how spatial learning to find food rewards in a hole-board maze modulates AHN (cell proliferation and immature neurons) and AHN related hippocampal neuroplasticity markers (BDNF, IGF-II and CREB phosphorylation) in mice. The Trained mice were tested for both spatial reference and working memory and compared to Pseudotrained mice (exposed to different baited holes in each session, thus avoiding the reference memory component of the task) and Control mice (exposed to the maze without rewards). In contrast to Pseudotrained and Control mice, the number of proliferating hippocampal cells were reduced in Trained mice, but they notably increased their population of immature neurons assessed by immunohistochemistry. This evidence shows that hole-board spatial reference learning diminishes cell proliferation in favour of enhancing young neurons survival. Interestingly, the enhanced AHN in the Trained mice (specifically in the suprapyramidal blade) positively correlated with their reference memory performance, but not with their working memory. Furthermore, the Trained animals increased the hippocampal protein expression of all the neuroplasticity markers analyzed by western blot. Results show that the appetitively-motivated hole-board task is a useful paradigm to potentiate and/or investigate AHN and hippocampal plasticity minimizing aversive variables such as fear or stress.

AMPK Modulates Associative Learning via Neuronal Mitochondrial Fusion inC. elegans

“…One major aspect which differentiates the nematode nervous system from the mammalian brain, is the fact that C. elegans , as a post mitotic organism, does not experience neurogenesis in the adult nematode. Adult hippocampal neurogenesis, or the production and integration of new neurons in the brain, which mainly occurs in the dentate gyrus in mammals(49), has been linked to learning and memory performance in both aversive association paradigms(50–52) and positive association paradigms(53), and is considered to have a crucial role in the hippocampal learning process. Although we cannot assess the relative contribution of adult neurogenesis to learning capacity in our system, we still observed a plasticity of the behavior in C. elegans after conditioning, suggesting that we are studying the intra-cellular processes involved in regulation of behavioral plasticity.…”

Long-term consequences of alcohol use in early adolescent mice: focus on neuroadaptations in GR, CRF and BDNF

“…Background staining was controlled in each section by calculating the average optical density levels from another part of the section without labelling (10 measures), and subtracting this value from the average measure of each region. For this purpose, we used ImageJ software (US National Institutes of Health, Maryland, USA) [46, 47].…”

The presence of a social stimulus reduces cocaine-seeking in a place preference conditioning paradigm

“…The distance between the selected sections was 225 µm. Immunohistochemistry was performed in free-floating sections using extravidin-conjugated peroxidase and diaminobenzidine as the chromogen with nickel at 0.04% as previously described (Castilla-Ortega et al, 2011; Sampedro-Piquero et al, 2018b). In order to investigate the neuronal activity pattern following the CPP test with or without the social stimulus, we studied the expression of the early immediate gene c-Fos (the primary antibody was the mouse monoclonal anti-c-Fos (sc-271243) Santa Cruz Biotechnology; diluted 1:1000).…”

“…The counting was conducted by an experimenter blind to the experimental condition. For this purpose, we used the software ImageJ (US National Institutes of Health, Maryland, USA) (Ladrón de Guevara-Miranda et al, 2017; Sampedro-Piquero et al, 2018b). Representative photographs of c-Fos immunoreactivity for each brain region analysed is shown in Figure 2 along with their Bregma levels.…”