[Abstract Title]. - Society for Neuroscience

Abstract: The pontine-wave (P-wave) is generated by the activation of a group of glutamateric
cells in the pons and is one of the most prominent phasic events of REM sleep. Recently we have
demonstrated that the P-wave generator activation-dependent two-way active avoidance
(TWAA) memory processing involves expression of brain-derived neurotrophic factor (BDNF)
in the CA3 subfield of the dorsal hippocampus (CA3-DH). The present study was designed to
examine whether TWAA memory processing-related BDNF expression in the CA3-DH is
mediated by the activation of protein kinase A (PKA). Adult male Sprague-Dawley rats (n=30)
were chronically implanted with sleep-wake recording electrodes and bilateral guide tubes for
microinjections into the CA3-DH. After postoperative recovery, rats were exposed to shuttle box
context (thirty minutes) and baseline sleep-wave activities were recorded between 10 AM and 4
PM for two consecutive days. One day after final baseline recording session, rats were placed in
the shuttle box and subjected to a session of 30 TWAA learning trials. Immediately after training
trials, rats were microinjected bilaterally with either KT-5720 (2.0 κmol in 200 nl/site; n=10
rats), a specific inhibitor of cAMP-dependent PKA activation, or control saline (200 nl/site; n=10
rats) into the CA3-DH. After microinjections, rats were recorded for sleep-wake activities for
six-hours (between 10 AM and 4 PM). Twenty-four hours after the training session, rats were
tested for TWAA memory. Another 10 rats received microinjection of KT-5720 in one side and
saline in other side. These rats were killed 3h after the end of microinjection to collect brain
tissue for measuring BDNF. The sleep-wake data revealed that compared to after control saline,
KT-5720 microinjections into the CA3-DH did not produce any significant changes in the
wakefulness, slow-wave sleep, or REM sleep. In the test trials of TWAA learning, however, KT-
5720 microinjected rats showed a significant deficit in the retention of TWAA memory. BDNF
results show that the amount of BDNF in the CA3-DH of KT-5720 treated side is 115 % less
than the saline treated side. These findings suggest that the activation of cAMP-PKA in the CA3-
DH is an important step for the consolidation and/or retention of TWAA memory but may not be
involved in the regulation of sleep-wake behavior. These results also indicated that the P-wave
generator activation-mediated expression of BDNF in the CA3-DH is mediated by the activation
of cAMP-PKA system.
Disclosures: S. Datta , None; J.L. Shea, None.
Poster
285. Sleep: Molecular, Cellular and Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 285.2/QQ18
Topic: E.08.c. Sleep: Molecular, cellular, and pharmacology
Support: Dept. of Veteran Affairs