Dr. Michael Meredith

Research Interest

Sensory physiology and brain circuits involved in chemosensory communication, including pheromones, studied by electrophysiological, anatomical and behavioral methods.

Current Projects

We study female to male and male to male signaling in golden hamsters and mice as a model to analyze sensory mechanisms - leading to sensory control of behavior. Expression of Immediate-Early Gene products such as Fos protein (from the c-fos gene) and electrophysiological-recording indicate which neurons in the brain change activity with:

• Chemosensory Stimulation
• Sexual Experience
• Hormone/ Neuromodulator Treatment (GnRH, Oxytocin, Dopamine, Androgen)

Our primary interest is in understanding the principles of brain-circuit operation and not the development of therapies. However, the unlearned recognition of chemo-sensory social signals that we study involves brain areas and circuits that have also been implicated in failures to recognize visual social signals, such as facial expressions, as in autism.

Sensory Pathway

• We have mapped a functional pathway from Vomeronasal-Organ (VNO) and Olfactory sensory-neurons in the nose - through successive brain regions - to a region known to be critical for male mating behavior.
• We study the effect of chemosensory input to this pathway. (For more information on VNO, see: Vomeronasal Organ Website) Neurons along this pathway are active in males stimulated only by chemosensory stimuli - as well as in males that are actually mating.
• The chemosensory stimuli used here are natural, pheromone-containing, secretions from females. The initial, chemosensory, parts of this pathway are also activated by natural chemosensory stimuli from males.
• Some part of this pathway must analyze the incoming neural signals in order to distinguish female and male stimuli from the same species, and to distinguish those socially-relevant stimuli from non-socially relevant stimuli that serve similar purposes but in another species.

Projects

Sorting Socially Relevant from Non-relevant Stimuli

• The neurons in the first two brain regions receiving chemosensory input: the accessory olfactory bulb (AOB) and the anterior medial amygdala (MeA) respond to all stimuli, female, male, socially relevant or not.
• Neurons in the posterior medial amygdala (MeP) only respond strongly to socially relevant stimuli (e.g. for hamsters, that means stimuli from female or male hamsters, NOT stimuli from mice: For mice, that means stimuli from female or male mice, not hamsters).
• The amygdala is known to be concerned with social and sexual behavior in many species. Can circuits in MeA "filter out" socially non- relevant input - and not pass it on to MeP - or inhibit activity there when input is not socially relevant?
• In mice, c-Fos is also activated in ventral posterior medial amygdala by a biologically relevant stimulus from different species. Cat odor activates c-Fos in groups of cells overlapping with those activated by male conspecific stimuli. Are there common elements to defensive behavior against other males and against predators?

Effect of Experience, GnRH, Oxytocin, Dopamine on Chemosensory Transmission

• Removal of vomeronasal organs seriously impairs male mating behavior in sexually inexperienced male hamsters, but surgery after sexual experience has no effect. I.E. Experience changes the circuit -- allowing olfactory input to substitute for VNO input. What are these changes at the circuit and molecular level?
• GnRH hormone infused in the brain restores mating behavior lost through VNO removal. GnRH is a neurohormone that acts on the pituitary but is also released in the brain. GnRH changes the circuit --allowing olfactory input to substitute for VNO input. What are these changes?
• Chemosensory activation of c-fos expression in medial amygdala changes with experience and with GnRH , but in different directions.
• Investigation of the changes in c-fos and electrical responses in the circuit with selective stimulation of VNO and olfactory systems reveals changes in transmission of chemosensory information as a result of these two manipulations.
• The amygdala is known to be involved with learning of certain types. Is the circuit for chemosensory-related learning similar to that (e.g.) for fear conditioning?
• Mice that lack Oxytocin expression (OT-KO) fail to recognize other mice they have encountered. The c-Fos expression in these mice suggests there is a failure of chemosensory mechanisms. We are using OT-KO and injections of Oxytocin-Antagonist (OT-A) to investigate the circuit modulation
• Dopamine modulates circuits in the amygdala to switch from a more cognitive (cortically driven) response to stimuli, to a more stereotyped (emotional?) response. The same dopamine-target neurons can also alter chemosensory circuits. Does DA modulate unlearned as well as learned responses?

Project under development

Amygdala Circuits that Discriminate Different Stimuli

A brain slice preparation is under development for investigating physiological connections, transmitters and molecular changes in circuits transmitting information from MeA to MeP that distinguish between stimuli.

Publications

• Meredith M, Brywczynski J, Slovis C. Attacking Asthma Five steps to treat pediatric status asthmaticus. JEMS. 34(10):26-28. (2009)
• Samuelsen CL, Meredith M. The vomeronasal organ is required for the male mouse medial amygdala response to chemical-communication signals, as assessed by immediate early gene expression. Neuroscience. NULL. (2009)
• Wilson DA, Baker H, Brunjes P, Gilbertson TA, Hermer L, Hill DL, Matsunami H, Meredith M, Mistretta CM, Smeets MA, Stowers L, Zhuang H. Chemoreception scientists gather under the Florida sun: The 31st Annual Association for Chemoreception Sciences meeting. Ann N Y Acad Sci. 1170 Suppl 1:1-11. (2009)
• Samuelsen CL, Meredith M. Categorization of biologically relevant chemical signals in the medial amygdala. Brain Res. 1263:33-42. (2009)
• Meredith MA, Allman BL, Keniston LP, Clemo HR. Auditory influences on non-auditory cortices. Hear Res. NULL. (2009)
• Leow AD, Zhu S, Zhan L, McMahon K, de Zubicaray GI, Meredith M, Wright MJ, Toga AW, Thompson PM. The tensor distribution function. Magn Reson Med. 61(1):205-14. (2009)
• Chou YY, Leporé N, Chiang MC, Avedissian C, Barysheva M, McMahon KL, de Zubicaray GI, Meredith M, Wright MJ, Toga AW, Thompson PM. Mapping genetic influences on ventricular structure in twins. Neuroimage. 44(4):1312-23. (2009)
• Brun C, Leporé N, Pennec X, Chou YY, Lee AD, Barysheva M, de Zubicaray G, Meredith M, McMahon K, Wright MJ, Toga AW, Thompson PM. A tensor-based morphometry study of genetic influences on brain structure using a new fluid registration method. Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv. 11(Pt 2):914-21. (2008)
• Shattuck DW, Chiang MC, Barysheva M, McMahon KL, de Zubicaray GI, Meredith M, Wright MJ, Toga AW, Thompson PM. Visualization tools for high angular resolution diffusion imaging. Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv. 11(Pt 2):298-305. (2008)
• Chiang MC, Barysheva M, Lee AD, Madsen S, Klunder AD, Toga AW, Mcmahon KL, de Zubicaray GI, Meredith M, Wright MJ, Srivastava A, Balov N, Thompson PM. Brain fiber architecture, genetics, and intelligence: a high angular resolution diffusion imaging (HARDI) study. Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv. 11(Pt 1):1060-7. (2008)
• de Zubicaray G, Postle N, McMahon K, Meredith M, Ashton R. Mirror neurons, the representation of word meaning, and the foot of the third left frontal convolution. Brain Lang. NULL. (2008)