title: Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.
abstract: 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 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 braintryptophan 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 not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing 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.
authors.affiliation: Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
authors.forename: Kaitlin S
authors.initials: KS
authors.lastname: Carlson
authors.affiliation: Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
authors.forename: Meredith S
authors.identifier: 0000-0002-1013-6599
authors.initials: MS
authors.lastname: Whitney
authors.affiliation: Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
authors.forename: Marie A
authors.identifier: 0000-0003-2435-8157
authors.initials: MA
authors.lastname: Gadziola
authors.affiliation: Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
authors.forename: Evan S
authors.identifier: 0000-0003-4211-9934
authors.initials: ES
authors.lastname: Deneris
authors.affiliation: Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
authors.forename: Daniel W
authors.identifier: 0000-0002-3192-3866
authors.initials: DW
authors.lastname: Wesson
mesh_terms: D000818:Animals; D001835:Body Weight; D004193:Discrimination Learning / Q000502:physiology*; D004192:Discrimination, Psychological / Q000502:physiology; D004326:Drinking / Q000502:physiology; D060766:Drinking Water; D056344:Executive Function / Q000502:physiology; D007266:Inhibition, Psychological; D008297:Male; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D055696:Olfactory Perception / Q000502:physiology*; D016548:Prosencephalon / Q000378:metabolism*; D012193:Reversal Learning / Q000502:physiology*; D012701:Serotonin / Q000096:biosynthesis*; D009435:Synaptic Transmission / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D060766:Drinking Water; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
keywords: 5-HT; odor discrimination; odor learning; operant behavior; psychophysics; reversal learning