We explore the neural processing of sensory information in the context of behavior. This line of questioning provides an ideal platform to test specific hypotheses regarding the neural basis of sensory dysfunction in neurological disorders, including dementias and addiction, wherein sensory processing is aberrant. To accomplish these major goals, we utilize a variety of methods, ranging from multi-site electrophysiological recordings or optical imaging from defined brain structures in behaving animals to cutting-edge operant behavioral assays, some of which we perform in viral/genetic animal models with precise neural perturbations. Our goals for our research include:
Define brain systems for sensory information processing and motivated behaviors:
The ventral striatum (VS) is an integrative network of brain structures, which: 1) processes sensory information, and 2) is necessary for both motivated behaviors and the rewarding effects of psychostimulants. The olfactory tubercle (OT) subregion of the VS resides in a likely advantageous position for guiding motivated behaviors, since it both receives monosynaptic input from the olfactory bulb and also has direct interconnectedness with other VS regions and the basal ganglia. The role of the OT in sensory-driven motivated behaviors is not defined.
A major line of research in our lab, therefore, is to identify manners whereby the OT encodes odor sensory information and to learn how this information consequently gets distributed throughout interconnected brain structures. We are also interested in defining sources of information into the OT. Work from our group is the first to demonstrate how neurons in the OT encode odor information in behaving subjects and how these processing strategies are shaped by the learned meaning of the odors (viz., valence). We are now working to identify complementary cellular mechanisms of odor valence and understand how this information is distributed among interconnected neural ensembles.
A related major line of research in our lab is regarding the OT’s role in motivated behaviors. Despite elegant work showing that the OT is needed for both reward behavior and psychostimulant effects on behavior, the OT is not even incorporated into many prevalent models of the brain’s reward system. This omission may in part be explained by a lack of the specific cellular mechanisms whereby the OT impacts reward-guided behavior. Work from our group is the first to demonstrate how neurons in the OT encode goal-directed actions and natural reinforcers and how these are dictated by the motivational state of the animal. Ongoing work in our lab is now resolving important features whereby the OT subserves motivated behaviors. This work is highly relevant to understanding brain mechanisms of addictive behaviors.
Determine why, and how, the olfactory system is vulnerable to early onset dementias, including Alzheimer’s disease and Parkinson’s disease:
A question of wide importance to our understanding of AD and PD is how these diseases progress. At a circuit level, this problem can be thought of specifically by the following question: How can subtle and sometimes undetectable levels of local pathogens result in severe, wide-spread nervous system dysfunction? We address this question in the mammalian olfactory system, which yields ideal tractability for physiological recordings as well as a nearly linear, yet also distributed, information processing stream. This is a clinically-relevant model, especially given the early presence of some AD and PD neuropathology (during early Braak & Braak stages) in the olfactory bulbs of persons afflicted with the disease. Our work seeks to allow the direct assessment of the cellular-level contributions of peripheral nervous dysfunction (‘upstream’) on central (‘downstream’) processing of behaviorally/perceptually-relevant information in the context of AD and PD and will therefore yield novel data on circuit progression of these diseases.
Define mechanisms whereby the olfactory system is shaped by cognitive state:
Cognition shapes sensory processing. Work by numerous groups has shown that olfactory perception and odor processing are both influenced by cognitive factors. The influence of attention, specifically, on the cellular processing of odors is entirely unknown. This is a very intriguing question, since olfactory cortical structures receive direct olfactory input in the absence of a thalamic relay—the proposed origin of attentionally-mediated effects in other sensory systems. Therefore, ongoing work in our lab has invested into developing a sophistical behavioral tool to allow for manipulating selective attention to odors and testing important questions regarding the mechanisms, whereby attention shapes the representation of odor information in the brain. This work is relevant for understanding how information travels within the brain in the context of moment-to-moment changes in cognitive state, which can be impacted in many neurological disorders.
- In ‘t Zandt EE, Cansler HL, Denson HB, Wesson DW. Centrifugal Innervation of the Olfactory Bulb: A Reappraisal. eNeuro. 2019 Feb 7;6(1). pii: ENEURO.0390-18.2019. doi: 10.1523/ENEURO.0390-18.2019. eCollection 2019 Jan-Feb.
- Carlson KS, Gadziola MA, Dauster ES, Wesson DW. Selective Attention Controls Olfactory Decisions and the Neural Encoding of Odors. Curr Biol. 2018 Jul 23;28(14):2195-2205.e4. doi: 10.1016/j.cub.2018.05.011. Epub 2018 Jun 28.
- Jagetia S, Milton AJ, Stetzik LA, Liu S, Pai K, Arakawa K, Mandairon N, Wesson DW. Inter- and intra-mouse variability in odor preferences revealed in an olfactory multiple-choice test. Behav Neurosci. 2018 Apr;132(2):88-98. doi: 10.1037/bne0000233. Epub 2018 Mar 1.
- Rey NL, Wesson DW, Brundin P. The olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases. Neurobiol Dis. 2018 Jan;109(Pt B):226-248. doi: 10.1016/j.nbd.2016.12.013. Epub 2016 Dec 20.
- Carlson KS, Whitney MS, Gadziola MA, Deneris ES, Wesson DW. Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis. eNeuro. 2016 Nov 17;3(5). pii: ENEURO.0257-16.2016. eCollection 2016 Sep-Oct.
- Buonviso N, Dutschmann M, Mouly AM, Wesson DW. Adaptation and Plasticity of Breathing during Behavioral and Cognitive Tasks. Neural Plast. 2016;2016:2804205. Epub 2016 Sep 29.
- Xiong A, Wesson DW. Illustrated Review of the Ventral Striatum’s Olfactory Tubercle. Chem Senses. 2016 Sep;41(7):549-55. doi: 10.1093/chemse/bjw069. Epub 2016 Jun 23. Review.
- Kimball BA, Wilson DA, Wesson DW. Alterations of the volatile metabolome in mouse models of Alzheimer’s disease. Sci Rep. 2016 Jan 14;6:19495. doi: 10.1038/srep19495.
- Gadziola MA, Wesson DW. The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum’s Olfactory Tubercle. J Neurosci. 2016 Jan 13;36(2):548-60. doi: 10.1523/JNEUROSCI.3328-15.2016.