Abstract

Hypothesis: The brain serotonin (5-HT) system is known to play a key role in regulating critical processes such as circadian clock timing, motivation, reward response and sleep. 5-HT knockout (SKO) mouse models have previously been used to understand 5-HT actions, but such global 5-HT depletion has profound non-targeted neurophysiological and developmental consequences. Therefore, conditional SKOs are needed. Here, we performed preliminary behavioral phenotyping in a conditional 5-HT knock down model where 5-HT synthesis blockade was targeted specifically to the midbrain raphe nuclear complex (site of hypothalamic serotonergic innervation) in adult mice.

Methods: Male Tph2-floxed mice were injected with AAV-Cre (experimental/ Tph2-/-) or blank AAV (control/ Tph2+/+) into the dorsal and median raphe nucleus (DRN and MRN). Animals were given 1wk to recover prior to experimentation. Behavior was monitored for a 2 wk post-injection period, during which circadian parameters (period [tau] nocturnal activity length [alpha] and daily activity bouts) were measured using overhead infrared motion detectors interfaced with a computerized data acquisition system.

Results and Conclusions: There was no difference in tau between Tph2-/- and Tph2+/+ (p < 0.05). Notably, there was a large difference in alpha, with Tph2-/- mice having longer alpha (p).

Keywords: serotonin, thp2, 5-ht, circadian, biological rhythms, raphe nucleus, dorsal raphe nucleus, median raphe nucleus, AAV-Cre, knockout mouse

Modified Abstract

Brain serotonin (5-HT) plays a key role in processes like circadian clock timing, reward response, and sleep. 5-HT knockout mouse models are used to understand 5-HT actions, but have non-targeted neurophysiological and developmental consequences. A conditional 5-HT knockdown model, where 5-HT synthesis is blocked in the raphe nucleus, was used for circadian phenotyping. Male Tph2-floxed mice were injected in the raphe nucleus with AAV-Cre (Tph2-/-) or blank AAV (Tph2+/+). Circadian parameters (period [tau], nocturnal activity length [alpha], and activity bouts) were monitored for 2 wks. Differences include Tph2-/- mice having longer alpha (p

Research Category

Biology/Ecology

Primary Author's Major

Biology

Mentor #1 Information

J. David Glass

Mentor #2 Information

Ashley Shemery

Mentor #3 Information

Alex Yaw

Presentation Format

Poster

Start Date

March 2016

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Research Area

Behavioral Neurobiology

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Mar 15th, 1:00 PM

Circadian Effects of the Conditional Knockdown of Serotonin in the Midbrain Raphe Nuclear Complex of adult mice

Hypothesis: The brain serotonin (5-HT) system is known to play a key role in regulating critical processes such as circadian clock timing, motivation, reward response and sleep. 5-HT knockout (SKO) mouse models have previously been used to understand 5-HT actions, but such global 5-HT depletion has profound non-targeted neurophysiological and developmental consequences. Therefore, conditional SKOs are needed. Here, we performed preliminary behavioral phenotyping in a conditional 5-HT knock down model where 5-HT synthesis blockade was targeted specifically to the midbrain raphe nuclear complex (site of hypothalamic serotonergic innervation) in adult mice.

Methods: Male Tph2-floxed mice were injected with AAV-Cre (experimental/ Tph2-/-) or blank AAV (control/ Tph2+/+) into the dorsal and median raphe nucleus (DRN and MRN). Animals were given 1wk to recover prior to experimentation. Behavior was monitored for a 2 wk post-injection period, during which circadian parameters (period [tau] nocturnal activity length [alpha] and daily activity bouts) were measured using overhead infrared motion detectors interfaced with a computerized data acquisition system.

Results and Conclusions: There was no difference in tau between Tph2-/- and Tph2+/+ (p < 0.05). Notably, there was a large difference in alpha, with Tph2-/- mice having longer alpha (p).

Keywords: serotonin, thp2, 5-ht, circadian, biological rhythms, raphe nucleus, dorsal raphe nucleus, median raphe nucleus, AAV-Cre, knockout mouse