Research Departments & Organizations
The main focus of the Verhagen lab is to explore the neural basis of flavor perception. Flavor perception has great relevance to the ongoing obesity epidemic, as it directly guides our daily food choices. Our approach to understanding the fundamental principles of human flavor perception is to use innovative rodent models that enable high resolution neurophysiological studies under conditions of controlled flavor experience. However, we know virtually nothing about how rodents perceive and process flavor. The lab has started to make significant advances in these areas by focussing on retronasal smell (i.e. smells arising from the mouth while eating food - the reaosn food doesnt "taste" like much when you have a cold) coding in the olfactory bulb.
Extensive Research Description
We have developed sophisticated methods for combining behavioral and neural methods, notably, optogenetic imaging and stimulation techniques in awake, unrestrained and even freely moving mice using a miniature wide-field microscope.
Neuro-behavioral basis of food perception
One of the main research areas is the neural encoding of retronasal smell. We optically image the input and output of the olfactory bulb in both rats and transgenic mice (GCaMP6). This work is NIH funded through 2021.
We are exploring the perceptual significance of small-scale temporal dynamics of the olfactory bulb. Here, Channel-Rhodopsin mice discriminate sniff-triggered movies projected onto their olfactory bulbs. This complex fully automated project has pinned down the minimal temporal discriminability of virtual odors to be ~13ms. We are in the process of refining these temporal coding hypotheses and applying it to both ortho- and retronasal smell.
We are also exploring the input-output relationship between optically stimulated glomeruli and electrophysiologically recorded mitral cells (spatio-temporal transfer functions). Thusfar we have established that sniffing of mice induces phase-gating of the input to reach the output of the olfactory bulb.
We are also testing the behaviors (sniffing, swallowing, movement, ingestion,etc) and concommitant neural responses in the olfactory bulb in head-fixed and freely-moving mice. We use Noldus video tracking for behavioral assessments.
Multi-modal imaging: OB fMRI, optical calcium and intrinsic imaging
Our interest in odor coding in the olfactory bulb has led to an additional collaboration with Dr. Fahmeed Hyder, Department of Biomedical Engineering, Director of MRRC and QNMR, Yale School of Medicine, with whom we are exploring the similarity in optically and micro-fMRI-imaged rats exposed to retro- and orthonasal odorants. This will allow both translation of rodent imaging to human work, and deeper understanding of whole-bulb food-related response patterns.
The lab is also one of seven labs of a large BRAIN Initiative NSF-funded (through end 2018) interdisciplinary effort to make substantial progress on our understanding of how animals navigate to odor sources. It is a high-profile project that has recieved lots of press, including in a series of PBS News Hour and PBS Science Scope. It includes mathematicians, a plume physicist, fly and rodent behavioral neurophysiologists.
We started working on virtual odor navigation, allowing us to explore the behavior and neural coding in the OB pertinent to odor navigation, in a virtual odor plume where all relevant parameters are under direct experimental control. This involves optical imaging and optogenetic stimulation of the OB.
Perception of odors linked to precise timing in the olfactory system.
Rebello MR, McTavish TS, Willhite DC, Short SM, Shepherd GM, Verhagen JV. Perception of odors linked to precise timing in the olfactory system. PLoS Biology 2014, 12:e1002021. 2014
Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mapping.
Sanganahalli BG, Rebello MR, Herman P, Papademetris X, Shepherd GM, Verhagen JV, Hyder F. Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: Implications for principles underlying odor mapping. NeuroImage 2016, 126:208-18. 2016
The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking.
Coronas-Samano G, Ivanova AV, Verhagen JV. The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking. Neural Plasticity 2016, 2016:9131284. 2016
Direct behavioral and neurophysiological evidence for retronasal olfaction in mice.
Rebello MR, Kandukuru P, Verhagen JV. Direct behavioral and neurophysiological evidence for retronasal olfaction in mice. PloS One 2015, 10:e0117218. 2015
Taste quality and intensity of 100 stimuli as reported by rats: the taste-location association task.
Gautam SH, Rebello MR, Verhagen JV. Taste quality and intensity of 100 stimuli as reported by rats: the taste-location association task. Frontiers In Behavioral Neuroscience 2012, 6:19. 2012