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Max Fletcher, PhD

Associate Professor
Department of Anatomy and 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

Education

  • PhD 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

Research Interests

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.

illustration

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.

Representative Publications

  • Ross JM, Bendahmane M, Fletcher ML. Olfactory Bulb Muscarinic Acetylcholine Type 1 Receptors Are Required for Acquisition of Olfactory Fear Learning. Front Behav Neurosci. 2019 Jul 19;13:164. doi: 10.3389/fnbeh.2019.00164. eCollection 2019. PubMed PMID: 31379534; PubMed Central PMCID: PMC6659260.
  • Ross JM, Fletcher ML. Aversive learning-induced plasticity throughout the adult mammalian olfactory system: insights across development. J Bioenerg Biomembr. 2019 Feb;51(1):15-27. doi: 10.1007/s10863-018-9770-z. Epub 2018 Aug 31. Review. PubMed PMID: 30171506; PubMed Central PMCID: PMC6382525.
  • Ogg MC, Ross JM, Bendahmane M, Fletcher ML. Olfactory bulb acetylcholine release dishabituates odor responses and reinstates odor investigation. Nat Commun. 2018 May 14;9(1):1868. doi: 10.1038/s41467-018-04371-w. PubMed PMID: 29760390; PubMed Central PMCID: PMC5951802.
  • Ross JM, Fletcher ML. Learning-Dependent and -Independent Enhancement of Mitral/Tufted Cell Glomerular Odor Responses Following Olfactory Fear Conditioning in Awake Mice. J Neurosci. 2018 May 16;38(20):4623-4640. doi: 10.1523/JNEUROSCI.3559-17.2018. Epub 2018 Apr 18. PubMed PMID: 29669746; PubMed Central PMCID: PMC5956984.
  • Mahan CE, Burnett AE, Fletcher ML, Spyropoulos AC. Extended thromboprophylaxis in the acutely ill medical patient after hospitalization - a paradigm shift in post-discharge thromboprophylaxis. Hosp Pract (1995). 2018 Feb;46(1):5-15. doi: 10.1080/21548331.2018.1410053. Epub 2017 Nov 30. Review. PubMed PMID: 29171776.
  • Fletcher ML, Ogg MC, Lu L, Ogg RJ, Boughter JD Jr. Overlapping Representation of Primary Tastes in a Defined Region of the Gustatory Cortex. J Neurosci. 2017 Aug 9;37(32):7595-7605. doi: 10.1523/JNEUROSCI.0649-17.2017. Epub 2017 Jul 3. PubMed PMID: 28674169; PubMed Central PMCID: PMC5551059.

View more references (pubmed link)

May 26, 2022