Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Biomedical Sciences



Research Advisor

Max Fletcher, Ph.D.


John D. Boughter, Jr., Ph.D. Matthew Ennis, Ph.D. Detlef H. Heck, Ph.D. Francesca-Fang Liao, Ph.D.


acetylcholine, calcium imaging, dishabituation, habituation, olfactory bulb


Habituation and dishabituation modulate the neural resources and behavioral significance allocated to incoming stimuli across the sensory systems. The purpose of the research presented in this dissertation was to characterize these processes in the mouse olfactory bulb (OB) and to determine if OB acetylcholine (ACh) has a role in physiological and behavioral olfactory dishabituation. Calcium imaging was used to determine the timecourse and magnitude of habituation in different parts of the OB during and after a prolonged odor presentation. Widefield imaging of the dendritic, or glomerular, response of OB output cells demonstrated that prolonged odor input habituates glomerular responses during the presentation as well as to subsequent presentations of the odor. Manipulation of OB ACh release during prolonged odor presentations using electrical stimulation dishabituated these decreased glomerular odor responses. A novel behavioral investigation paradigm was developed to see how prolonged odor input affects odor salience in awake, behaving mice. Optogenetic stimulation of OB cholinergic neurons rapidly modulated odor salience in this paradigm, causing mice to suddenly investigate a previously ignored odor. Non-olfactory sensory stimulation also dishabituated odor investigation and this increase could be blocked pharmacologically with a cholinergic antagonist in the OB, demonstrating the ecological validity of this ACh effect. Two-photon imaging revealed that, unlike the glomerular responses, soma responses of different OB cell types can be quite different from each other during a prolonged odor presentation. These results highlight the need for future studies that explore the role of different OB cell types in the representation of olfactory information over time and behavioral dishabituation.