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

Selected Publications

Meredith, M., Samuelsen, C., Blake, C, Westberry, J. 2007, Selective response of medial amygdala subregions to reproductive and defensive chemosignals from conspecific and heterospecific species. Chem. Signals in Vertebrates 11: in press. Preprint
Nolte, C.M. and Meredith, M. 2005, mGluR2 activation of medial amygdala input impairs vomeronasal organ-mediated behavior. Physiology and Behavior 86:314-323.
Meredith, M. and Westberry, JM 2004 Distinctive responses in the medial amygdala to same and different species pheromones. J. Neuroscience 24:5719-5725 PDF
Westberry, J. M. and Meredith, M. 2003 Pre-exposure to female chemosignals or intracerebral GnRH restores mating behavior in naïve male hamsters with vomeronasal organ lesions. Chemical Senses 28:191-196.
Westberry, J. M. and Meredith, M. 2003 The influence of chemosensory input and gonadotropin releasing hormone on mating behavior circuits in male hamsters. Brain Res.974:1-16
Meredith, M. 2003 "Vomeronasal Organ" - Contribution to The Encyclopedia of Neuroscience. 3rd. Ed., G. Adelman and B.H. Smith (Eds.) New York NY, Elsevier. (new updated version)
Fewell, G.D and Meredith, M. 2002 Experience facilitates vomeronasal and olfactory influence on Fos expression in medial preoptic area during pheromone exposure or mating in male hamsters. Brain Res. 941: 91-106i PDF
Meredith, M.and Fewell, G.D. 2001 Vomeronasal Organ: Electrical Stimulation Activates FOS in Mating Pathways and in GnRH Neurons. Brain Res. 922:87-94 PDF
Meredith, M. 2001 Human Vomeronasal Organ: A critical review of best and worst cases. Chem. Senses 26:433:445. PDF
Kelliher, K., Baum, M. and Meredith, M. 2001 The Ferret's vomeronasal organ and accessory olfactory bulb: Effect of hormone manipulation in adult males and females. Anat. Rec. 263:280-288. Abstract
Meredith, M. 1999 Vomeronasal Organ. In: Encyclopedia of Reproduction, E. Knobil and J.D. Niell (eds) pp. 1004-1014. Academic Press
Fernandez-Fewell, G.D. and Meredith, M. (1998) Olfactory contribution to Fos expression during mating in inexperienced male hamsters. Chem. Senses 23, 257-267. Abstract
Meredith, M. (1998) Vomeronasal, olfactory, hormonal convergence in the brain: Co-operation or coincidence. Olfaction and Taste XII; Ann. N.Y. Acad. Sci. 855:349-361 Abstract
Moeller, J.F. and Meredith, M. 1998 Increase in gonadotropin-releasing hormone (GnRH) levels in CSF after stimulation of nervus terminalis in Atlantic stingray, Dasyatis sabina. Brain Res. 806:104-7

Abstracts

Samuelsen C. and Meredith, M. 2008 Medial Amygdala Response after Vomeronasal Organ Removal to Territorial, Reproductive and Predator Stimuli. 2008 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. PDF
Blake, CB, Meredith, M. 2007 Effects of Gonadotropin-Releasing Hormone (GnRH) on Main Olfactory Input to the Medial Amygdala in Male Hamsters. 2007 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. PDF
Samuelsen, CL, Meredith, M. 2007 Responses in the Medial Amygdala to Territorial, Reproductive and Predator Chemosensory Stimuli. Society for Behavioral Neuroendocrinology: In press
Blake, CB, Meredith, M.2006 Facilitation and suppression of main olfactory input to the medial amygdala by gonadotropin-releasing hormone (GnRH) in intact and VNX male hamsters. 2006 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.
Samuelsen C. and Meredith, M. 2006 Categorization of Species-Specific odors by Medial Amygdala. 2006 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.
Samuelsen C, Westberry JM, Meredith, M. 2004 Categorization of chemosensory information in medial amygdala of male hamsters and male mice. 2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.
Westberry JM and Meredith, M.2004 Automatic categorization of conspecific pheromone stimuli by medial amygdala requires vomeronasal input in sexually naive male hamsters but is lost in experienced males. 2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience.