Biological Science Faculty Member
Dr. Michael Meredith
Ph.D., University of Pennsylvannia, 1974
Research and Professional Interests:
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, in particular those leading to sensory control of behavior. Expression of immediate-early gene products such as Fos- and FRA-proteins (from the c-fos gene or related genes) are used as markers to indicate which neurons in the brain change activity under different conditions, including:
- Chemosensory Stimulation
- Sexual Experience
- Hormone/ Neuromodulator Treatment (GnRH, Oxytocin, Dopamine, Androgen)
Direct recording of neuronal electrical activity can also be used in some circumstances.
Our primary interest is in understanding the principles of brain-circuit operation and not the development of therapies, but the unlearned recognition of chemosensory 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 the VNO, see the 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 socially nonrelevant stimuli that serve similar purposes but in another species.
Sorting Socially Relevant from Nonrelevant 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, and from various species.
- 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). This neural response reflects (or maybe causes?) normal behavioral responses.
- The amygdala is known to be concerned with social and sexual behavior in many species. Can circuits in the MeA "filter out" nonrelevant input—and not pass it on to the MeP—or inhibit activity there when input is not relevant?
- In mice, the FRA activity-marker is also turned on in the ventral posterior medial amygdala by a biologically relevant stimulus from different species. Cat odor activates FRA in groups of cells overlapping with those activated by male conspecific stimuli. Do defensive behaviors against other males and against predators share common elements?
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 into the brain restores mating behavior lost through VNO removal. GnRH is a neurohormone that acts on the pituitary gland but is also released inside 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 neuronal “circuit" for chemosensory-related learning similar to that for (e.g.) fear conditioning?
- Mice that lack Oxytocin expression (OT-KO) fail to recognize other mice they have previously encountered. The c-Fos expression in these mice suggests a failure of chemosensory mechanisms. Injections of oxytocin antagonist (OT-A, which blocks OT action) eliminates medial amygdala response to chemical signals, including cat odor, and mice no longer avoid cat odor. Oxytocin appears to be necessary for both the normal amygdala response and for normal behavioral recognition of the meaning of stimuli.
- 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. Current experiments evaluate whether DA modulates unlearned as well as learned responses?
(Links to abstracts and to full text of some publications are available through "Personal Home Page," above.)
Witt, M., and M. Meredith. In press. The human vomeronasal duct. In: Management of Smell and Taste Disorders, edited by T. Hummel and A. Welge-Lussen. G. Thieme, Stuttgart.
Samuelsen, C. L., and M. Meredith. 2011. Oxytocin antagonist disrupts male mouse medial amygdala response to chemical-communication signals. Neuroscience 180:96-104. PDF
Blake, C. B., and M. Meredith. 2011. Change in number and activation of androgen receptor immuno-reactive cells in the medial amygdala in response to chemosensory input. Neuroscience 190:228-238. PDF
Moeller, J., and M. Meredith. 2010. Differential co-localization with choline acetyl transferase in Nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo). Brain Research 1366:44-53. PDF
Blake, C. B., and M. Meredith. 2010. Selective enhancement of main olfactory input to medial amygdala by GnRH. Brain Research 1317:46-59. PDF
Samuelsen, C. L., and M. Meredith. 2009. The vomeronasal organ is required for the male mouse medial amygdala response to chemical-communication signals, as assessed by immediate early gene expression. Neuroscience 164:1468-1476. PDF
Samuelsen, C. L., and M. Meredith. 2009. Categorization of biologically relevant chemical signals in the medial amygdala. Brain Research 1263:33-42. PDF
Meredith, M., C. L. Samuelsen, C. B. Blake, and J. M. Westberry. 2008. Selective response of medial amygdala subregions to reproductive and defensive chemosignals from conspecific and heterospecific species. Chemical Signals in Vertebrates 11:367-378. PDF
Nolte, C. M., and M. Meredith. 2005. mGluR2 activation of medial amygdala input impairs vomeronasal organ-mediated behavior. Physiology and Behavior 86:314-323. PDF
Meredith, M., and J. M. Westberry. 2004. Distinctive responses in medial amygdala to same- and different-species pheromones. Journal of Neuroscience 24:5719-5725. PDF
Westberry, J. M., and M. Meredith. 2003. The influence of chemosensory input and gonadotropin releasing hormone on mating behavior circuits in male hamsters. Brain Research 974:1-16. PDF
Meredith, M. 2001. Human vomeronasal organ: a critical review of best and worst cases. Chemical Senses 26: 433-445. PDF