College of Arts & Sciences

Kim Huhman

Research

General Interests. The unifying theme of the research in my laboratory is neuroendocrinology and behavior. We employ a variety of methods from molecular to behavioral observation. Our techniques include in situ hybridization histochemistry, immunohistochemistry, tract tracing and microinjection of pharmacological agents into the brain. These methods help elucidate the physiological processes that underlie the behaviors in which we are interested.

Social Stress/Aggression/Conditioned Defeat. Conditioned defeat is a long-lasting and profound behavioral response displayed by male Syrian hamsters following a brief defeat in the home cage of a larger, more aggressive opponent. Following the initial defeat, hamsters fail to produce normal territorial aggression, but instead display only submissive and defensive behaviors even though they are now tested in their own home cages and a smaller, non-aggressive intruder (NAI) is used as the opponent. We have shown that conditioned defeat can persist for at least 33 days following the initial defeat even if the hamster experiences no additional defeat.

It has been hypothesized that changes in the balance between glutamatergic and GABAergic neurotransmission in the amygdala are critical for regulating behavioral responses to anxiety provoking and aversive stimuli. We have demonstrated that an increase in GABAergic neurotransmission in the amygdala, either during the initial defeat (training) or during testing with a NAI, blocks the acquisition and expression of conditioned defeat. Muscimol, a GABAA agonist, dose-dependently and selectively reduces submissive and defensive behavior exhibited during testing when the drug is given either before training or before testing. This effect is not due to a general sedation caused by muscimol as other social and non-social behaviors are not effected by the injections. Furthermore, muscimol given before training did not alter the behavior of the aggressive trainer nor does it alter the pain responsiveness of the defeated animals as measured with a standard hot-plate test. The data indicate that an increase in GABAergic transmission in the amygdala can block the acquisition and expression of conditioned defeat. We have also shown that a decrease in glutamatergic neurotransmission in the amygdala can block the acquisition and expression of conditioned defeat. AP5, a NMDA glutamate receptor antagonist, given either before training or before testing selectively reduces submissive/defensive behaviors exhibited during testing. Together, these data indicate that changes in amino acid neurotransmission in the amygdala can alter response to anxiety provoking and aversive stimuli in hamsters.

Corticotropin releasing factor (CRF) is known to modulate autonomic and behavioral responses to a number of stressors. We have shown that intracerebroventricular CRF exacerbates conditioned defeat, while a CRF receptor antagonist (non-selective for R1 and R2) significantly attenuates the submissive/defensive behavior produced by hamsters following defeat. A selective CRF-R1 antagonist was ineffective. We have subsequently demonstrated that the non-selective CRF antagonist is effective in attenuating conditioned defeat when infused into the bed nucleus of the stria terminalis but not when infused into the central amygdala.

The most effective treatment in blocking conditioned defeat that we have employed to date is the opiate drug, buprenorphine, which is a partial mu receptor agonist and a kappa receptor antagonist. Buprenorphine, when given systemically immediately after defeat training, abolishes submissive behaviors produced by defeated hamsters during testing and reinstates species-typical territorial aggression. We are currently using selective mu agonists and kappa antagonists to determine which action of buprenorphine accounts for its effects.

We are also using viral vector gene transfer to change the expression of genes in the amygdala that are thought to be critical for the formation of fear memories. We have used a modified herpes simplex virus to overexpress CREB (cyclic AMP response element binding protein) in the basolateral amygdala. We have found that HSV-CREB animals exhibit exaggerated submissive behaviors when compared with animals that were injected with the control virus.

We have attempted to test defeated hamsters in a variety of tasks that have been pharmacologically validated in other rodents (i.e., rats and sometimes mice) as measuring anxiety. We have tested hamsters in defensive withdrawal and open field paradigms, and have obtained variable, and sometimes unexpected, results. Much of the difficulty appears to arise from the fact that hamsters, unlike rats, do not respond to stress-provoking situations with freezing and immobility. Instead, hamsters appear to display more active defensive reactions (i.e., fleeing). Thus, it has not been possible thus far for us to draw conclusions about the role of anxiety-like processes in conditioned defeat.

Circadian Rhythms. Circadian rhythms in mammals (i.e., daily variations in activity, neurotransmitters and hormones) are not simply a response to the daily light:dark cycle but are an endogenous property of a group of cells in the hypothalamus called the suprachiasmatic nucleus (SCN). A considerable amount is known about the neurochemical composition of the SCN, how the SCN receives information about light from the environment and how the SCN synchronizes or entrains itself to the light:dark cycle. We are currently exploring how the SCN then drives the rhythmic variation in its outputs, a topic that has received relatively little attention. In particular, we hope to elucidate the manner in which the SCN times the rhythmic release of luteinizing hormone (necessary for ovulation in females) and adrenocortical hormones (glucocorticoids) in Syrian hamsters, a species that is very useful in research on circadian rhythms because they are strongly photoperiodic.

Recent publications

Huhman, K. L.; Jasnow, A. M.; Sisitsky, A. S.; Albers, H. E. Rhythms in glutamic acid decarboxylase mRNA in constant darkness. Brain Research, 851, 266-269, 1999.

Jasnow, A. M.; Banks, M. C.; Owens, E. C.; Huhman, K. L. Differential effects of two corticotropin-releasing factor antagonists on conditioned defeat in male, Syrian hamsters (Mesocricetus auratus). Brain Research, 846, 122-128, 1999.

Jasnow, A. M.; Huhman, K. L.; Bartness, T. J.; Demas, G. E. Short-day increases in aggression are inversely related to circulating testosterone concentrations in male Siberian hamsters (Phodopus sungorus). Hormones and Behavior, 38, 102-110, 2000.

Whitten, R.; Jasnow, A. M.; Albers, H. E.; Huhman, K. L. The effects of endomorphin-1 on conditioned defeat in Syrian hamsters (Mesocricetus auratus). Brain Research, 914, 74-80, 2001.

Jasnow, A. M.; Drazen, D. L.; Huhman, K. L.; Nelson, R. J.; Demas, G. E. Acute and chronic social defeat suppresses humoral immunity of male Syrian hamsters (Mesocricetus auratus). Hormones and Behavior, 40, 428-433, 2001.

Jasnow, A. M.; Huhman, K. L. Activation of GABAA receptors in the amygdala blocks the acquisition and expression of conditioned defeat in Syrian hamsters. Brain Research, 920, 142-150, 2001.

Harmon, A. C.; Moore, T. O.; Huhman, K. L.; Albers, H. E. Social experience and social context alter the behavioral response to centrally administered oxytocin in female Syrian hamsters. Neuroscience, 109, 767_772, 2002.

Mintz, E. M.; Jasnow, A. M.; Gillespie, C. F.; Huhman, K. L.; Albers, H. E. GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts. Neuroscience, 109, 773-778, 2002.

Jasnow, A.J., Huhman, K.L., Bartness, T.J., Demas, G.E. Short days and exogenous melatonin increase aggression of male Syrian hamsters (Mesocricetus auratus). Hormones and Behavior, 42, 13-20, 2002.

Harmon, A. C.; Huhman, K. L.; Moore, T. O.; Albers, H. E. Oxytocin inhibits aggression in female Syrian hamsters. Journal of Neuroendocrinology, 14, 963-969, 2002.

Huhman, K. L.; Solomon, M. B.; Janicki, M.; Harmon, A. C.; Lin, S. M.; Israel, J. E. Jasnow, A. M. Conditioned defeat in male and female Syrian hamsters. Hormones and Behavior, 44, 293-299, 2003.

Jasnow, A. M.; Cooper, M. A.; Huhman, K. L. N-methyl-D-aspartate receptors in the amygdala are necessary for the acquisition and expression of conditioned defeat. Neuroscience, 123, 625-634, 2004.

Jasnow, A. M.; Davis, M., Huhman, K. L. Involvement of central amygdalar and bed nucleus of the stria terminalis corticotropin-releasing factor in behavioral responses to social defeat. Behavioral Neuroscience, 118, 1052-1061, 2004.

Novak, C. M.; Ehlen, C.; Huhman, K. L.; Albers, H. E. GABAB receptor activation in the suprachiasmatic nucleus of diurnal and nocturnal rodents. Brain Research Bulletin, 63, 531-535, 2004

Faruzzi, A. N.; Solomon, M. B.; Demas, G.E.; Huhman, K. L. Gonadal hormones modulate the display of submissive behaivor in socially defeated female Syrian hamsters. Hormones and Behavior, in press.

Lab members

Current members:
Matthew Cooper, Ph.D., Postdoctoral Associate
Diane Day-Balch, Ph.D., Postdoctoral Associate
Alicia Faruzzi, Graduate Research Assistant
Matia Banks Solomon, Graduate Research Assistant
Stacie Lin, Graduate Research Assistant
Lauren Runge, Laboratory Technician

Past members and current affiliation:
Aaron Jasnow, Ph.D. (Rockefeller University, Postdoctoral Associate)
Alicia Askew, Ph.D. (Presbyterian College, Assistant Professor)