RT Journal Article
SR Electronic
T1 Preservation of essential odor-guided behaviors and odor-based reversal learning after targeting adult brain serotonin synthesis
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0257-16.2016
DO 10.1523/ENEURO.0257-16.2016
A1 Kaitlin S. Carlson
A1 Meredith S. Whitney
A1 Marie A. Gadziola
A1 Evan S. Deneris
A1 Daniel W. Wesson
YR 2016
UL http://www.eneuro.org/content/early/2016/10/27/ENEURO.0257-16.2016.abstract
AB The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether or not the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 (Tph2), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 targeted mice were not only able to learn the task, but also had similar levels of odor acuity as compared to control mice when performing a coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.Significance Statement: Modulation of sensory systems by neurotransmitters is considered critical for perception. The olfactory system is robustly innervated by 5-HT neurons into both its primary and secondary odor processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. Here we asked whether the olfactory system needs 5-HT by using a conditional genetic approach to specifically target adult brain 5-HT synthesis and nearly eliminate 5-HT from the mouse forebrain. Our results suggest that 5-HT neurotransmission is not required for the most essential aspects of olfaction, including odor learning, odor discrimination, and odor-based cognitive flexibility. These findings raise questions about the importance and precise role of 5-HT modulation in olfactory system circuitry.