A single link to the first track to allow the export script to build the search page
  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    485—Learning and Memory: Physiology II

    Monday, November 11, 2013, 1:00 pm - 5:00 pm

    485.12: Circadian and cognitive costs of nocturnal activity for a diurnal brain

    Location: Halls B-H

    ">*C. A. MARTIN-FAIREY1, L. SMALE2, A. A. NUNEZ2;
    1Michigan State University|910004099|0, East Lansing, MI; 2Psychology, Michigan State Univ., East Lansing, MI

    Abstract Body: People who have a misalignment between activity and the sleep wake cycle often experience impairment in cognitive functions. In order to study the relationship between circadian misalignment and impaired cognition, we used a shift worker rodent model, the diurnal grass rat (Arvicanthis niloticus). Although these animals are strongly diurnal in the field and under standard laboratory conditions, a subset of them becomes night active (NA) when given access to running wheels, while the rest continues to be day active (DA). This remarkable shift in phase preference for the display of activity by NA grass rats is accompanied by a phase reversal in the rhythmic expression of PER 1 and 2 in the hippocampus. Thus, in NA grass rats, the phase of that local circadian oscillator is similar to that of nocturnal species and is 1800 out of phase with that of DA grass rats. Grass rats without a running wheel show superior retention of a hippocampal dependent task, the Morris water maze (MWM), when the training and testing occur during the day as compared to the night. Here we report a replication of that effect in DA grass rats, and document in NA grass rats deficits in both acquisition and retention of the MWM, which are apparent regardless of the time of training and testing. Additionally, we monitored the expression of FOS protein, an immediate early gene product used as a marker for neuronal activation, in CA1 and observed that the rhythmic expression of FOS showed a 1800 reversal when NA and DA grass rats were compared. Thus, similar to rhythms in hippocampal PER1and 2, the pattern of FOS expression in the NA grass rat resembles that of nocturnal mammals. However, not all hippocampal rhythms of NA grass rats show a full phase reversal. For example, the rhythm of Trk B expression, a gene product associated with learning and plasticity, is only phase delayed by 4 hours in CA1 when grass rats adopt a NA profile. Further, other regions of the brain that show rhythmic expression of PER 1and 2 and are involved in the regulation of the sleep-wake cycle retain their diurnal profile in NA grass rats. Taken together these results indicate that for a diurnal species, choosing to be active during the rest phase results in cognitive impairments that may stem from a misalignment among hippocampal as well as extra-hippocampal circadian rhythms. Similar circadian disruptions may be responsible for the cognitive deficits reported for human shift workers.

    Lay Language Summary: We all find optimal times for performing a variety of tasks, with most of us being more competent during the day than during the night, which is expected since humans have evolved as a predominantly diurnal species. We have used the Nile grass rat, a diurnal mammal, as an animal model to study the mechanisms responsible for the circadian modulation of cognitive functions that results in optimal times of day for learning and for retaining what is learned, in a fashion that matches the diurnal or nocturnal life style of the species. In sharp contrast to what has been reported in nocturnal laboratory rats, in grass rats the memory of tasks that require spatial navigational abilities is acutely diminished when the learning takes place at night. Additionally, our laboratory has shown that in brain regions involved in cognition, there is a daily rhythmic expression of gene products important for learning and memory. Interestingly, peak expression of these gene products occurs during the day in our diurnal animal model, the opposite of what is reported for nocturnal species. Thus, our work provides evidence for a day- time advantage for cognitive functions that coincides with peak expression of gene products important for learning and memory, in an animal model that, like humans, is active during the day and rests at night.
    Eveningness is a human condition characterized by extensive nocturnal activity. While humans are clearly diurnal, in our 24/7 global society, nocturnal activity is becoming more and more prevalent. Eveningness is associated with a multitude of negative outcomes, including poor learning and memory. Further, humans that engage in sustained nocturnal activity, for example night shift workers and most college freshmen, are at risk for a variety of physical and psychological pathologies including obesity, eating disorders and overall poor quality of life. Progress in the understanding of the mechanisms that mediate the negative outcomes of nocturnal activity in humans has been hampered by the lack of an animal model that would display two key features: (1) being diurnal like our own species and (2) being capable of showing voluntary switches from a day active to a night active profile of activity. Our grass rats meet those two demands. Thus, in spite of being strongly diurnal in the field and under standard laboratory conditions, if given access to exercise wheels, a subset of our animals “voluntarily” becomes night active exhibiting an activity pattern that resembles human eveningness.
    To test the effects of nocturnal activity in a normally diurnal animal, we tested day active and night active grass rats on a spatial memory task, the Morris water maze, during the day or night. The day active animals showed the expected enhanced performance when tested during the day, but the night active animals were deficient regardless of the time of day of testing. We also monitored the expression of gene products associated with learning, memory, and arousal in areas of the brain that support cognition. While the day active animals showed the patterns typical of this diurnal species, the night active animals showed a compromise between diurnal and nocturnal features. We conclude that when individuals of a diurnal species like ours becomes active at an inappropriate time, the night, cognitive abilities suffer due to a lack of synchrony among circadian aspects of the neural systems that mediate learning and memory.

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

    485—Learning and Memory: Physiology II

    Monday, November 11, 2013, 1:00 pm - 5:00 pm

    485.12: Circadian and cognitive costs of nocturnal activity for a diurnal brain

    Location: Halls B-H

    ">*C. A. MARTIN-FAIREY1, L. SMALE2, A. A. NUNEZ2;
    1Michigan State University|910004099|0, East Lansing, MI; 2Psychology, Michigan State Univ., East Lansing, MI

    Abstract Body: People who have a misalignment between activity and the sleep wake cycle often experience impairment in cognitive functions. In order to study the relationship between circadian misalignment and impaired cognition, we used a shift worker rodent model, the diurnal grass rat (Arvicanthis niloticus). Although these animals are strongly diurnal in the field and under standard laboratory conditions, a subset of them becomes night active (NA) when given access to running wheels, while the rest continues to be day active (DA). This remarkable shift in phase preference for the display of activity by NA grass rats is accompanied by a phase reversal in the rhythmic expression of PER 1 and 2 in the hippocampus. Thus, in NA grass rats, the phase of that local circadian oscillator is similar to that of nocturnal species and is 1800 out of phase with that of DA grass rats. Grass rats without a running wheel show superior retention of a hippocampal dependent task, the Morris water maze (MWM), when the training and testing occur during the day as compared to the night. Here we report a replication of that effect in DA grass rats, and document in NA grass rats deficits in both acquisition and retention of the MWM, which are apparent regardless of the time of training and testing. Additionally, we monitored the expression of FOS protein, an immediate early gene product used as a marker for neuronal activation, in CA1 and observed that the rhythmic expression of FOS showed a 1800 reversal when NA and DA grass rats were compared. Thus, similar to rhythms in hippocampal PER1and 2, the pattern of FOS expression in the NA grass rat resembles that of nocturnal mammals. However, not all hippocampal rhythms of NA grass rats show a full phase reversal. For example, the rhythm of Trk B expression, a gene product associated with learning and plasticity, is only phase delayed by 4 hours in CA1 when grass rats adopt a NA profile. Further, other regions of the brain that show rhythmic expression of PER 1and 2 and are involved in the regulation of the sleep-wake cycle retain their diurnal profile in NA grass rats. Taken together these results indicate that for a diurnal species, choosing to be active during the rest phase results in cognitive impairments that may stem from a misalignment among hippocampal as well as extra-hippocampal circadian rhythms. Similar circadian disruptions may be responsible for the cognitive deficits reported for human shift workers.

    Lay Language Summary: We all find optimal times for performing a variety of tasks, with most of us being more competent during the day than during the night, which is expected since humans have evolved as a predominantly diurnal species. We have used the Nile grass rat, a diurnal mammal, as an animal model to study the mechanisms responsible for the circadian modulation of cognitive functions that results in optimal times of day for learning and for retaining what is learned, in a fashion that matches the diurnal or nocturnal life style of the species. In sharp contrast to what has been reported in nocturnal laboratory rats, in grass rats the memory of tasks that require spatial navigational abilities is acutely diminished when the learning takes place at night. Additionally, our laboratory has shown that in brain regions involved in cognition, there is a daily rhythmic expression of gene products important for learning and memory. Interestingly, peak expression of these gene products occurs during the day in our diurnal animal model, the opposite of what is reported for nocturnal species. Thus, our work provides evidence for a day- time advantage for cognitive functions that coincides with peak expression of gene products important for learning and memory, in an animal model that, like humans, is active during the day and rests at night.
    Eveningness is a human condition characterized by extensive nocturnal activity. While humans are clearly diurnal, in our 24/7 global society, nocturnal activity is becoming more and more prevalent. Eveningness is associated with a multitude of negative outcomes, including poor learning and memory. Further, humans that engage in sustained nocturnal activity, for example night shift workers and most college freshmen, are at risk for a variety of physical and psychological pathologies including obesity, eating disorders and overall poor quality of life. Progress in the understanding of the mechanisms that mediate the negative outcomes of nocturnal activity in humans has been hampered by the lack of an animal model that would display two key features: (1) being diurnal like our own species and (2) being capable of showing voluntary switches from a day active to a night active profile of activity. Our grass rats meet those two demands. Thus, in spite of being strongly diurnal in the field and under standard laboratory conditions, if given access to exercise wheels, a subset of our animals “voluntarily” becomes night active exhibiting an activity pattern that resembles human eveningness.
    To test the effects of nocturnal activity in a normally diurnal animal, we tested day active and night active grass rats on a spatial memory task, the Morris water maze, during the day or night. The day active animals showed the expected enhanced performance when tested during the day, but the night active animals were deficient regardless of the time of day of testing. We also monitored the expression of gene products associated with learning, memory, and arousal in areas of the brain that support cognition. While the day active animals showed the patterns typical of this diurnal species, the night active animals showed a compromise between diurnal and nocturnal features. We conclude that when individuals of a diurnal species like ours becomes active at an inappropriate time, the night, cognitive abilities suffer due to a lack of synchrony among circadian aspects of the neural systems that mediate learning and memory.