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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    095—Learning and Memory: Physiology I

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    95.05: Adult neurogenesis protects against proactive interference

    Location: Halls B-H

    ">*J. R. EPP1, R. SILVA MERA1, L. C. P. BOTLY1, A. C. GIANLORENCO2, S. K÷HLER3, S. A. JOSSELYN1, P. W. FRANKLAND1;
    1Program in Neurosciences and Mental Hlth., Hosp. For Sick Children, Toronto, ON, Canada; 2Federal Univ. of Sao Carlos, Sao Carlos, Brazil; 3Psychology, Univ. of Western Ontario, London, ON, Canada

    Abstract Body: Neurogenesis occurs throughout life in the mammalian hippocampus. As a result, there is continuous remodeling of the hippocampal circuitry as the new neurons form connections with existing cellular networks. This type of plasticity has potential implications for the storage and/or clearance of previously acquired memories. We hypothesized that increasing the addition of new neurons after learning may decrease the stability of a hippocampus-dependent memory. Conversely, decreasing neurogenesis after learning should help to stabilize a hippocampus-dependent memory. To test these hypotheses, mice were trained in one of three hippocampus dependent tasks, a spatial version of the Morris water task, a touchscreen based object-location paired associates task and a digging mediated odour-context paired associates task. Following training environmental (voluntary running) or pharmacological (weekly administration of the NMDAR antagonist, memantine) interventions were used to increase adult neurogenesis or a conditional genetic (HSV-TK mice) approach was used to reduce neurogenesis. Four weeks following experimental elevation or reduction of adult neurogenesis we measured retention of the previously acquired memories and conducted reversal learning. In all three tasks our results show that a post-training increase of neurogenesis causes a decrease in retention of previously acquired hippocampus-dependent memories. However, when subjected to reversal learning, mice with elevated levels of neurogenesis outperformed mice with normal levels of neurogenesis. Conversely, reduction in neurogenesis resulted in enhanced retention of the previously acquired memories and produced impairment in reversal learning. Finally, the impact of voluntary running on retention of previously-acquired memory and on reversal learning was blocked in the HSV-TK mice, indicating that these effects are mediated by a neurogenic mechanism. The results described here show that adult neurogenesis aids in the clearance or inhibition of hippocampal memories, perhaps those that are outdated or no longer necessary. As a result new learning can occur more efficiently due to decreased proactive interference from the previous memories.

    Lay Language Summary: Our results indicate that the continuous production of new neurons (neurogenesis) in the adult brain results in forgetting of old memories and consequently facilitates acquisition of new memories. These findings describe a novel mechanism that allows the brain to reduce memory interference and may shed light on the memory deficits associated with numerous disorders.
    Many problems with memory, including those associated with aging, arise from an inability to distinguish between different yet similar episodes. This leads to a condition known as proactive interference, where previously acquired memories impair new learning. In order to overcome this type of interference it is thought to be necessary for the brain to eliminate redundant or outdated memory traces so that new or more important memories can be acquired successfully. Our research has uncovered an important mechanism that allows for a reduction in proactive interference in the face of highly interfering memories. Namely, the continuous addition of new neurons to the existing circuitry of the hippocampus reduces the stability of previously acquired memories.
    The hippocampus, an area of the brain that is critical for many forms of learning and memory is one of only two regions of the brain that continues to produce new neurons throughout adult life. The function of these newly produced neurons has been highly debated. Numerous studies have suggested that neurogenesis might be important for learning and memory, but it was not clear specifically what these new neurons were for. A common belief is that more new neurons should be beneficial for learning and memory. However, there is also a strong possibility that adding new neurons to an existing circuit will decrease the signal to noise ration and make it difficult to maintain stable memories. Therefore, we hypothesized that neurogenesis may provide a mechanism to reduce the stability of previously acquired memories.
    To test this hypothesis we trained mice on several hippocampus-dependent learning tasks and then either increased or decreased the rate of neurogenesis over a period of 4 weeks. We then tested how well the mice remembered the original memories. Mice with normal levels of neurogenesis showed a normal intact memory. Mice with increased neurogenesis showed impaired memory and mice with reduced neurogenesis showed enhanced memory. The same mice then acquired a second memory that was either highly similar or less similar to the original memory. Mice with increased neurogenesis were able to quickly acquire the highly similar memory while those with normal or reduced neurogenesis took a significantly longer time to learn the new memory. If the mice were trained to learn a memory that was dissimilar to the original then all groups showed an equal learning ability. This indicates that neurogenesis plays a specific role in reducing memory interference that arises from the acquisition of similar memories.
    Future work will focus on determining whether increasing neurogenesis can modulate the amount of memory interference that occurs in aged mice or in models of impaired memory.

    Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    095—Learning and Memory: Physiology I

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    95.05: Adult neurogenesis protects against proactive interference

    Location: Halls B-H

    ">*J. R. EPP1, R. SILVA MERA1, L. C. P. BOTLY1, A. C. GIANLORENCO2, S. K÷HLER3, S. A. JOSSELYN1, P. W. FRANKLAND1;
    1Program in Neurosciences and Mental Hlth., Hosp. For Sick Children, Toronto, ON, Canada; 2Federal Univ. of Sao Carlos, Sao Carlos, Brazil; 3Psychology, Univ. of Western Ontario, London, ON, Canada

    Abstract Body: Neurogenesis occurs throughout life in the mammalian hippocampus. As a result, there is continuous remodeling of the hippocampal circuitry as the new neurons form connections with existing cellular networks. This type of plasticity has potential implications for the storage and/or clearance of previously acquired memories. We hypothesized that increasing the addition of new neurons after learning may decrease the stability of a hippocampus-dependent memory. Conversely, decreasing neurogenesis after learning should help to stabilize a hippocampus-dependent memory. To test these hypotheses, mice were trained in one of three hippocampus dependent tasks, a spatial version of the Morris water task, a touchscreen based object-location paired associates task and a digging mediated odour-context paired associates task. Following training environmental (voluntary running) or pharmacological (weekly administration of the NMDAR antagonist, memantine) interventions were used to increase adult neurogenesis or a conditional genetic (HSV-TK mice) approach was used to reduce neurogenesis. Four weeks following experimental elevation or reduction of adult neurogenesis we measured retention of the previously acquired memories and conducted reversal learning. In all three tasks our results show that a post-training increase of neurogenesis causes a decrease in retention of previously acquired hippocampus-dependent memories. However, when subjected to reversal learning, mice with elevated levels of neurogenesis outperformed mice with normal levels of neurogenesis. Conversely, reduction in neurogenesis resulted in enhanced retention of the previously acquired memories and produced impairment in reversal learning. Finally, the impact of voluntary running on retention of previously-acquired memory and on reversal learning was blocked in the HSV-TK mice, indicating that these effects are mediated by a neurogenic mechanism. The results described here show that adult neurogenesis aids in the clearance or inhibition of hippocampal memories, perhaps those that are outdated or no longer necessary. As a result new learning can occur more efficiently due to decreased proactive interference from the previous memories.

    Lay Language Summary: Our results indicate that the continuous production of new neurons (neurogenesis) in the adult brain results in forgetting of old memories and consequently facilitates acquisition of new memories. These findings describe a novel mechanism that allows the brain to reduce memory interference and may shed light on the memory deficits associated with numerous disorders.
    Many problems with memory, including those associated with aging, arise from an inability to distinguish between different yet similar episodes. This leads to a condition known as proactive interference, where previously acquired memories impair new learning. In order to overcome this type of interference it is thought to be necessary for the brain to eliminate redundant or outdated memory traces so that new or more important memories can be acquired successfully. Our research has uncovered an important mechanism that allows for a reduction in proactive interference in the face of highly interfering memories. Namely, the continuous addition of new neurons to the existing circuitry of the hippocampus reduces the stability of previously acquired memories.
    The hippocampus, an area of the brain that is critical for many forms of learning and memory is one of only two regions of the brain that continues to produce new neurons throughout adult life. The function of these newly produced neurons has been highly debated. Numerous studies have suggested that neurogenesis might be important for learning and memory, but it was not clear specifically what these new neurons were for. A common belief is that more new neurons should be beneficial for learning and memory. However, there is also a strong possibility that adding new neurons to an existing circuit will decrease the signal to noise ration and make it difficult to maintain stable memories. Therefore, we hypothesized that neurogenesis may provide a mechanism to reduce the stability of previously acquired memories.
    To test this hypothesis we trained mice on several hippocampus-dependent learning tasks and then either increased or decreased the rate of neurogenesis over a period of 4 weeks. We then tested how well the mice remembered the original memories. Mice with normal levels of neurogenesis showed a normal intact memory. Mice with increased neurogenesis showed impaired memory and mice with reduced neurogenesis showed enhanced memory. The same mice then acquired a second memory that was either highly similar or less similar to the original memory. Mice with increased neurogenesis were able to quickly acquire the highly similar memory while those with normal or reduced neurogenesis took a significantly longer time to learn the new memory. If the mice were trained to learn a memory that was dissimilar to the original then all groups showed an equal learning ability. This indicates that neurogenesis plays a specific role in reducing memory interference that arises from the acquisition of similar memories.
    Future work will focus on determining whether increasing neurogenesis can modulate the amount of memory interference that occurs in aged mice or in models of impaired memory.