Max Fletcher, Ph.D.
Department of Anatomy & Neurobiology
The University of Tennessee Health Science Center
855 Monroe Avenue
Memphis, TN 38163
Phone: (901) 448-2212
Fax: (901) 448-7193
Email: Max Fletcher
- Ph.D. Institution: University of Oklahoma, Department of Zoology
- Postdoctoral: Yale University Medical School, Department of Neurobiology; University of Texas Medical School at Houston, Department of Neurobiology and Anatomy
My research focuses on understanding the basic principles of neural encoding of sensory information and how both experience and learning can affect this process. Specifically, my work has focused on investigating how simple forms of learning can enhance sensory processing in the early stages of the olfactory pathway and lead to changes in perception. To accomplish this, I have employed a broad range of techniques including in vivo electrophysiology, awake and anesthetized in vivo imaging, in vivo two-photon calcium imaging, and as well as behavioral approaches.
Olfactory Bulb Imaging
In the olfactory system, receptor neurons expressing the same receptor type project their axons onto one or a few specific glomeruli on the olfactory bulb surface. This unique organization allows odorants to be encoded as spatial patterns of activity. To visualize these odor representations within the bulb, we use optical imaging methods combined with transgenic mouse lines expressing genetically encoded indicators of neuronal activity.
Left: Dorsal view of the mouse olfactory bulb. Middle: GCaMP2 glomerular activation patterns to three different odorants in the same mouse expressed in different color channels. Right: Overlay of activity patterns into one image. In this case color combinations represent glomeruli responsive to the different odorants. For example, yellow glomeruli respond to both ethyl butyrate and methyl valerate. As can be seen, similar odorants activate partially overlapping, but distinct sets of glomeruli.
Olfactory Bulb Glomerular Plasticity
Within the olfactory bulb, odors are represented as topographical maps of olfactory sensory neuron input. This input can be modulated by both intrinsic inhibitory circuits within the bulb as well as by centrifugal input from several learning-related regions of the brain that project into the olfactory bulb. Using in vivo imaging in both awake and anesthetized mice, we are investigating how these circuits are involved in driving learning-induced changes in glomerular processing. Current work is focused on comparing odorant-evoked in vivo activity patterns in the same animal before and after different combinations of odor presentations, associative conditioning, direct activation of neuromodulatory brain regions, and pharmacological manipulation. These studies will have a significant impact on our understanding of the neural basis of odor coding and role plasticity plays in shaping neural responses to sensory stimuli.
Olfactory Associative Learning and Discrimination
Classical conditioning teaches an animal to associate a previously neutral stimulus with another stimulus of some significance. In the case of olfaction, this paradigm can also lead to enhanced discrimination of the associated odor, a process known as perceptual learning. Using an olfactory fear conditioning paradigm, our lab seeks to understand the neural mechanisms underlying this learning and subsequent behavioral expression. Current work is focused on the role neuromodulators play in the acquisition and expression of this type of learning.
- Nagayama S, Fletcher ML, Xiong W, Lu X, Zeng S, Chen WR. In vivo local dye electroporation for Ca²⁺ imaging and neuronal-circuit tracing. Cold Spring Harb Protoc. 2014 Sep 2;2014(9):940-7. doi: 10.1101/pdb.prot083501. PubMed PMID: 25183821.
- Fletcher ML, Bendahmane M. Visualizing olfactory learning functional imaging of experience-induced olfactory bulb changes. Prog Brain Res. 2014;208:89-113. doi: 10.1016/B978-0-444-63350-7.00004-8. Review. PubMed PMID: 24767480.
- Pavesi E, Heldt SA, Fletcher ML. Neuronal nitric-oxide synthase deficiency impairs the long-term memory of olfactory fear learning and increases odor generalization. Learn Mem. 2013 Aug 16;20(9):482-90. doi: 10.1101/lm.031450.113. PubMed PMID: 23955171.
- Kikuta S, Fletcher ML, Homma R, Yamasoba T, Nagayama S. Odorant response properties of individual neurons in an olfactory glomerular module. Neuron. 2013 Mar 20;77(6):1122-35. doi: 10.1016/j.neuron.2013.01.022. PubMed PMID: 23522047; PubMed Central PMCID: PMC3607817.
- Pavesi E, Gooch A, Lee E, Fletcher ML. Cholinergic modulation during acquisition of olfactory fear conditioning alters learning and stimulus generalization in mice. Learn Mem. 2012 Dec 14;20(1):6-10. doi: 10.1101/lm.028324.112. PubMed PMID: 23242418; PubMed Central PMCID: PMC3533131.
- Fletcher ML. Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses. Front Syst Neurosci. 2012 Mar 22;6:16. doi: 10.3389/fnsys.2012.00016. eCollection 2012. PubMed PMID: 22461771; PubMed Central PMCID: PMC3309973.