The role of adult hippocampal neurogenesis in reducing interference.

Adult neurogenesis in the hippocampal dentate gyrus plays an important role in learning and memory. However, the precise contribution of the new neurons to hippocampal function remains controversial. Emerging evidence suggests that neurogenesis is important for pattern separation and for mitigating interference when similar items must be learned at different times. In the present study, we directly test this prediction using a recently developed olfactory memory task that has those specific features. In this task, rats learn two highly interfering lists of odor pairs, one after the other, in either the same or in different contexts. Consistent with our hypothesis, focal cranial irradiation, resulting in selective reduction of neurogenesis within the dentate gyrus, significantly impaired the ability to overcome interference during learning of the second list. The ability to learn a single odor list was unimpaired. We also show that irradiation had no effect on learning in a hippocampal-dependent spatial alternation task. Although both tasks involved learning interfering responses, the time course for learning the interfering items differed. Learning the interfering odor lists took place sequentially, over the course of several sessions, whereas learning the interfering spatial locations took place concurrently, within each session. Thus, the gradual addition of new neurons may have provided a pattern separation mechanism for the olfactory task but not for the maze task. These findings demonstrate a role for neurogenesis in resolving interference and they are consistent with models suggesting a critical role for neurogenesis in pattern separation.

[1]  S. Becker,et al.  A model of hippocampal neurogenesis in memory and mood disorders , 2007, Trends in Cognitive Sciences.

[2]  Suzanna Becker,et al.  Adult hippocampal neurogenesis and memory interference , 2012, Behavioural Brain Research.

[3]  Marc W Howard,et al.  Gradual Changes in Hippocampal Activity Support Remembering the Order of Events , 2007, Neuron.

[4]  Jason S. Snyder,et al.  Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. , 2001, Journal of neurophysiology.

[5]  E. Kandel,et al.  Paradoxical influence of hippocampal neurogenesis on working memory , 2007, Proceedings of the National Academy of Sciences.

[6]  Jason S. Snyder,et al.  Inhibition of neurogenesis interferes with hippocampus‐dependent memory function , 2006, Hippocampus.

[7]  S. Becker A computational principle for hippocampal learning and neurogenesis , 2005, Hippocampus.

[8]  Janet Wiles,et al.  Computational Influence of Adult Neurogenesis on Memory Encoding , 2009, Neuron.

[9]  Suzanna Becker,et al.  Computational modeling and empirical studies of hippocampal neurogenesis-dependent memory: Effects of interference, stress and depression , 2009, Brain Research.

[10]  E. Gould,et al.  Stress, stress hormones, and adult neurogenesis , 2012, Experimental Neurology.

[11]  J. Epp,et al.  Activation and survival of immature neurons in the dentate gyrus with spatial memory is dependent on time of exposure to spatial learning and age of cells at examination , 2011, Neurobiology of Learning and Memory.

[12]  Janet Wiles,et al.  Potential role for adult neurogenesis in the encoding of time in new memories , 2006, Nature Neuroscience.

[13]  F. Gage,et al.  Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons , 2010, Proceedings of the National Academy of Sciences.

[14]  David M. Smith,et al.  Learning-Related Development of Context-Specific Neuronal Responses to Places and Events: The Hippocampal Role in Context Processing , 2006, The Journal of Neuroscience.

[15]  L. Saksida,et al.  A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation , 2009, Science.

[16]  A. Eisch,et al.  Reduction of Adult Hippocampal Neurogenesis Confers Vulnerability in an Animal Model of Cocaine Addiction , 2010, The Journal of Neuroscience.

[17]  J. Epp,et al.  Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation , 2007, Neuroscience.

[18]  Sean M. Polyn,et al.  Memory search and the neural representation of context , 2008, Trends in Cognitive Sciences.

[19]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[20]  David M. Smith,et al.  Hippocampal place cells, context, and episodic memory , 2006, Hippocampus.

[21]  B. Jacobs,et al.  Adult brain neurogenesis and psychiatry: a novel theory of depression , 2000, Molecular Psychiatry.

[22]  David Dupret,et al.  Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons , 2007, PLoS biology.

[23]  Lisa M. Saksida,et al.  Running enhances spatial pattern separation in mice , 2010, Proceedings of the National Academy of Sciences.

[24]  F. Gage,et al.  New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? , 2010, Nature Reviews Neuroscience.

[25]  David M. Smith,et al.  Hippocampal context processing is critical for interference free recall of odor memories in rats , 2012, Hippocampus.

[26]  T. Shors,et al.  Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons. , 2007, Learning & memory.