Cyclin D2 knockout mice with depleted adult neurogenesis learn Barnes maze task.

Abstract

There is a broad discussion concerning the function of new neurons in the adult brain. An increasingly accepted hypothesis proposes their crucial role in spatial learning. In this work, however, we demonstrate adult cyclin D2 knockout (cD2 KO) mice, which lack adult hippocampal neurogenesis, are able to learn a spatial version of the Barnes maze. Similar to wild type (WT) controls, these mutant mice exhibited several indicators of learning during 6 days of training: successively shorter latency and distance, higher speed, and decreasing number of errors. WT and cD2 KO mice showed improved search strategies, which became increasingly spatial. During probe Trial 1, mutant mice attained the highest significant number of nose-pokes at the former target hole compared with all the other holes. Both WT and cD2 KO mice covered shorter distances during probe Trial 2, whereas the mutant mice showed higher speed. We also discuss the possibility that some of the observed differences displayed by cD2 KO mice during training and at the probe trials-for example, longer mean distance and more errors-are associated with a smaller hippocampal formation. Our results suggest that adult brain neurogenesis is not obligatory for learning the Barnes maze.

Sodium Butyrate, a Histone Deacetylase Inhibitor, Exhibits Neuroprotective/Neurogenic Effects in a Rat Model of Neonatal Hypoxia-Ischemia

“…Consistent with these findings, many studies have shown that experimental reduction of adult neurogenesis impairs hippocampal memory formation and conversely, stimulated neurogenesis seems to be one approach to enhance cognitive recovery. On the other hand, contradictory accounts showed no impact of adult brain neurogenesis reduction on memory formation, where the role of newly generated neurons has previously been strongly suggested [43, 82, 83]. In the view of this inconsistent data, a stronger link between increased neurogenesis in the injured brain and functional outcome after treatment with HDACis needs to be pursued with future work.…”

Distinguishing adaptive plasticity from vulnerability in the aging hippocampus

“…First, the reduction of granule cell proliferation begins in middle age, before significant age-related changes in hippocampal-dependent memory are typically detected. Second, even if new neurons normally do play a role in hippocampal memory encoding (Aimone et al, 2006; Frankland, 2013; Piatti et al, 2013), data exist that suggest that neurogenesis may not be necessary for intact spatial learning (Jaholkowski et al, 2009; Arruda-Carvalho et al, 2011; Martinez-Canabal et al, 2013; Urbach et al, 2013). In fact, experiments in aged rats suggest that those old rats with lower levels of neurogenesis paradoxically show better spatial learning capacity (Bizon et al, 2004; Bizon and Gallagher, 2005).…”

“…In fact, experiments in aged rats suggest that those old rats with lower levels of neurogenesis paradoxically show better spatial learning capacity (Bizon et al, 2004; Bizon and Gallagher, 2005). The observations that blocking adult neurogenesis does not always result in a negative cognitive phenotype in adult mice (Urbach et al, 2013), and that reduced neurogenesis in aged rats is associated with better cognition, suggests a different framework for understanding the role of adult-born granule cells. It has been suggested that a small population of recently-generated granule cells normally participate in the encoding of most experiences, while the majority of granule cells are effectively silent, and typically do not participate in creation of new representations (Alme et al, 2010).…”

Neurogenic evangelism: Comment on Urbach et al. (2013).

“…Detailed analysis of the behavior indicated that cyclin D2 knockout mice Correspondence concerning this article should be addressed to Paul W. Frankland, Program in Neurosciences and Mental Health, The Hospital for Sick Children, Departments of Psychology and Physiology, University of Toronto, Toronto, Ontario, Canada M5G 1X8. E-mail: paul .frankland@sickkids.ca acquired this form of spatial leaming as quickly as controls, used equivalently "spatial" search strategies in finding the target hole and showed equivalent spatial bias in a probe test conducted at the end of training (Urbach et al, 2013). So, despite having no adult neurogenesis, cyclin D2 knockout mice were quite able to form a spatial memory.…”