SLEEP 2011 Abstract Supplement

A. Basic Science IX. Learning, Memory and Cognition
Conclusion: Here we demonstrate that the overnight consolidation of
episodic memory normally present in the healthy young brain is impaired
in older adults. Moreover, this age-related impairment appears to
be mediated by a failure of slow-wave sleep consolidation mechanisms
that facilitate systems-level reorganization in hippocampal-neocortical
networks.
Support (If Any): Supported by National Institutes of Health; NIH NIA
[RO1AG031164] (MPW), [F32AG039170](BAM).
0230
IMPAIRED HIPPOCAMPAL-DEPENDENT LEARNING
IN OLDER ADULTS MEDIATED BY DEFICIENT SLEEP-
SPINDLE GENERATION
Mander BA 1 , Rao V 1 , Lu BS 3 , Saletin JM 1 , Jagust WJ 2 , Walker MP 1,2
1
Psychology, University of California, Berkeley, Berkeley, CA, USA,
2
Helen Wills Neuroscience Institute, University of California, Berkeley,
Berkeley, CA, USA, 3 Division of Pulmonary and Critical Care
Medicine, California Pacific Medical Center, San Francisco, CA, USA
Introduction: Recent evidence in young adults suggests that NREM
sleep-spindles restore hippocampal-dependent memory encoding ability,
promoting efficient post-sleep learning. Aging is associated both with
impaired hippocampal-dependent learning and disrupted NREM sleep,
yet the causal interaction between these factors remains unknown. Combining
EEG and fMRI, here we examine whether age-related deficits in
sleep-spindle generation lead to a compromised next-day ability to form
hippocampal-dependent episodic memories.
Methods: Twenty-three participants, divided between healthy older
adults (n=12, 70.5±1.6 years) and healthy young adults (n=11, 20.2±0.6
years) obtained a full night of polysomnographically recorded sleep
(whole-head, 19-channel-EEG), followed the next day by a hippocampal-dependent
episodic learning task performed during event-related
fMRI.
Results: Following sleep, older adults exhibited a 49% deficit in nextday
episodic learning ability relative to young adults (p=0.013), further
paralleled by significant deficits in hippocampal-encoding activation.
Co-occurring with these neural and behavioral impairments was a
30% reduction in sleep-spindle density in older adults (p=0.045), most
prominent over frontal cortex. In young adults, the density of frontal
sleep-spindles accurately predicted next-day hippocampal-encoding
activation (r=0.68, p=0.022), and learning ability (r=0.63, p=0.038). In
contrast, this mediating spindle relationship with next-day hippocampal
activation and concomitant learning ability was lost in old adults (all
r0.35). Indeed, the strength of predictive association between
frontal sleep-spindles and next-day hippocampal-encoding activity differed
significantly between the young and old groups (p=0.018).
Conclusion: Here we demonstrate that the restitutive benefit of sleep on
next-day hippocampal-dependent encoding ability in the healthy young
brain is impaired in older adults. Moreover, such age-related memory
impairment appears to be mediated by a failure in the generation of
sleep-spindles, specifically over frontal cortex, leading to a compromised
ability to form new episodic memories. Such findings suggest that
sleep disruption in the elderly is an overlooked but potentially significant
mediating factor contributing to cognitive decline in later life.
Support (If Any): Supported by National Institutes of Health; NIH NIA
[RO1AG031164] (MPW), [F32AG039170](BAM).
0231
DIFFERENCES IN SOCIAL INTERACTION BETWEEN
OEXIN/ATAXIN-3 AND WILDTYPE MICE
Xie XS 1 , Yang L 1 , Zou B 1 , Sakurai T 2
1
AfaSci Research Laboratory, AfaSci, Inc., Redwood City, CA, USA,
2
Department of Molecular Neuroscience and Integrative Physiology,
Kanazawa University, Kanazawa-shi, Japan
Introduction: Hypocretins/orexin (Hcrt) regulates general behaviors
e.g., wake/sleep, locomotion, feeding, and reward. The Hcrt system has
been also implicated in exploring behavior, stress response, learning and
memory. To test the hypothesis that Hcrt plays a role in social interaction,
we used a validated protocol that two enclosures with either a
strange or littermate mouse are placed in a normal home cage to investigate
social interaction of the test subject of either wildtype (WT) or
orexin/ataxin-3 (AT) mice, in which the Hcrt neurons almost completely
degenerated after 4 postnatal weeks.
Methods: General behavior and social interaction were automatically
quantified using AfaSci’s home cage monitoring system-SmartCage.
The social interaction test was conducted in light phase and consisted
of three consecutive 10-min sessions: 1) Habituation, the test mouse explored
two empty enclosures; 2) Sociability: one stranger (from different
cage) or littermate mouse was randomly placed in one enclosure; 3)
Preference for social novelty: a new unfamiliar mouse (stranger 2) was
placed into the other enclosure. The CageScoreTM software calculated
occupancy time of the test mouse in two different zones corresponding
to the enclosures. Active counts, active time, traveling distance and
velocity, and rearing counts of the test mouse were also automatically
analyzed.
Results: When using stranger 1 for sociability test and stranger 2 for
social novelty test, there were no significant differences in both interactions
between the genotypes. When using littermate for sociability test,
the WT test subject did not show any sociability. In contrast, the AT
subject exhibited a similar degree of sociability as seen with the stranger
1. In the consequent social novelty test using a stranger there were no
significant differences between the two genotypes (n=8 per genotype).
The AT mice significantly decreased in active counts, active time, travel
distance (but not velocity), and rearing counts compared to the WT littermates
during the dark period in a 24-h recording.
Conclusion: The AT mice have normal social interaction ability as the
WT mice. However, the AT mice treat their littermates as strangers and
show great interest in exploring during the sociability test, suggesting
that the AT mice may have social memory deficits compared to WT littermates.
The AT mice displayed a decrease in wake activity, locomotion
and rearing during the dark phase compare to their WT littermates.
Support (If Any): NIH grants R01 MH078194 and R43NS065555
0232
ELECTROPHYSIOLOGICAL EVIDENCE OF IMPACT ON
AUDITORY PRE-ATTENTIVE BRAIN MECHANISM IN
HABITUAL SHORT SLEEPERS: STUDY I
Gumenyuk V, Roth T, Jefferson C, Drake C
Sleep Disorders & Research Center, Henry Ford Hospital, Detroit, MI,
USA
Introduction: Reduced TIB relative to biological sleep-need is common.
The impact of habitual short sleep on automatic (pre-attentive)
auditory processing has not been studied to date. An established electrophysiological
index of pre-attentive auditory processing is the fronto-centrally
distributed event-related potential (ERP) called mismatch
negativity (MMN). The current study investigates the effects of chronic
- 6h/night of sleep on frontal brain areas involved in auditory attention.
Methods: 10 self-defined short sleepers (2-wk diary TST≤6h) (age:
35±10yrs, 5F) and 9 subjects with TST=7-8h, (age: 30±6yrs, 6F) participated.
ERPs were recorded via a 64-EEG channel system. Two test
conditions: “ignore” and “attend” were implemented in a standard odd-
SLEEP, Volume 34, Abstract Supplement, 2011
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