Our research examines the interrelationships among social interactions, hormones, growth factors, adult neurogenesis, and spatial cognition.

The Spritzer Lab studies the effects of hormones and social interactions on hippocampus physiology and associated cognitive abilities, using rodents as model systems.  Students in our research group are testing how testosterone and growth factors influence adult neurogenesis and spatial memory in male rodents, with particular interest in treating age-related memory loss.  Additional field experiments involve testing the relationships among sex steroids, natural ranging behavior, and neural turn-over in the hippocampus of wild voles.  Here are our four current lines of research in greater detail:

Dose-dependent effects of testosterone on spatial memoryPast experiments testing the activational effects of testosterone on memory have produced mixed results, both in humans and rodents. Our initial experiments demonstrated that castration impaired spatial working memory among male rats but had minimal effect on long-term memory. Subsequent experiments showed that testosterone injections given to castrated rats could restore spatial working memory and that testosterone could improve long-term memory on certain spatial tasks. We further showed that the effects of testosterone on spatial memory exhibit a complex dose-response relationship, whereby high and low physiological doses of testosterone improve working memory but an intermediate dose does not. We have demonstrated this relationship among both young and aged male rats, indicating that testosterone can improve memory in the aged brain. The underlying cause of the relationship between testosterone and working memory seems to involve the relative effects of testosterone on different brain regions: a low dose of testosterone biases males toward the use of a striatum-dependent response strategy and a high dose of testosterone biases males toward the use of a hippocampus-dependent place strategy. The mechanism for this effect seems to involve up-regulation of BDNF in the corresponding brain regions, but the ability for testosterone to influence BDNF levels may be impaired in the aged brain. Continuing research is exploring the physiological pathways by which testosterone influences place and response learning.  The results have implications for the treatment of age-related memory loss.

  • Spritzer, M.D.,D. Daviau*, M.K. Coneeny*, S.M. Engelman*, W.T. Prince*, and K.N. Rodriguez-Wisdom*. 2011. Effects of testosterone on spatial learning and memory in adult male rats. Hormones and Behavior, 59: 484-496, doi: 10:1016/j.yhbeh.2011.01.009.
  • Spritzer, M.D., D. Fox*, G.E Larson*, C. Batson*, B. Wagner*, J.E. Maher*. 2013. Testosterone influences spatial strategy preferences among adult male rats. Hormones and Behavior, 63: 800-812, doi: 10.1016/j.yhbeh.2013.03.018.
  • Wagner, B.A.*, V.C. Braddick*, C.G. Batson*, B.H. Cullen*, L.E. Miller*, M.D. Spritzer. 2018. Effects of testosterone dose on spatial memory among castrated adult male rats. Psychoneuroendocrinology, 89: 120–130, doi: 1016/j.psyneuen.2017.12.025.
  • Zhang K.J.*, R.A. Ramdev*, N.J. Tuta*, M.D. Spritzer. Dose-dependent effects of testosterone on spatial learning strategies and brain-derived neurotrophic factor in male rats. Psychoneuroendocrinology, 121, 104850. doi.org/10.1016/j.psyneuen.2020.104850

Testosterone and adult neurogenesis—New neurons continue to develop in the hippocampus throughout adulthood, and understanding the function and physiological regulation of adult neurogenesis holds promise for the treatment of neurodegenerative diseases (e.g., Alzheimer’s disease and chronic depression). Paralleling our research on the relationship between testosterone and memory, we tested the role of testosterone in regulating adult neurogenesis within the hippocampus, again using adult male rats as our model. We showed that testosterone had no effect on cell proliferation within the hippocampus, but testosterone injections did enhance the survival of new neurons. Dihydrotestosterone injections enhanced neurogenesis in males, whereas estradiol did not, suggesting that testosterone has its effects on neurogenesis through an androgen-dependent pathway. We have conducted experiments giving rats testosterone injections during different stages of neural development, which have shown that testosterone has its strongest effects during the later stages of neural integration within the hippocampus. On-going experiments will further clarify which stages of neuronal development are most sensitive to testosterone, and whether these effects are entirely androgen-dependent or occur through other physiological pathways.

  • Spritzer, M.D. and L.A.M. Galea. 2007. Testosterone and dihydrotestosterone, but not estradiol, enhance hippocampal neurogenesis in adult male rats. Developmental Neurobiology, 67: 1321-1333, doi: 1002/dneu.20457.
  • Spritzer, M.D., Ibler*, W. Inglis*, and M.G. Curtis*. 2011. Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats. Neuroscience, 195: 180-190, doi: 10.1016/j.neuroscience.2011.08.034.
  • Spritzer, M.D., K.M.K. Calhoun*, E.A. Roy*, Z.E. Schneider-Lynch*, J. M. Barker, L.A.M. Galea. 2014. Effects of testosterone on stages of neural development in the dentate gyrus of adult male rats. Society for Neuroscience Annual Meeting. Washington, D.C.
  • Spritzer, M.D. and E.A. Roy*. 2020. Testosterone and adult neurogenesis. Biomolecules, 10: 225, doi:10.3390/biom10020225

Effects of social interactions on adult neurogenesis—Besides the effects of testosterone on adult neurogenesis, our laboratory has also explored the effects of socio-sexual interactions on adult neurogenesis. Past evidence indicated that adult neurogenesis plays a role in social memory formation, but the effects may be dependent upon the nature of the interaction. Older collaborative work with Drs. Liisa Galea and Victor Viau demonstrated that a combination of an acute stressor and a sexual interaction enhanced cell proliferation within the hippocampus beyond that observed in response to either of these events alone. Further work showed that repeated sexual interactions with different females reduced neurogenesis relative to repeated interactions with the same female. This suggests that repeated social interactions may reinforce the stability of newly formed neurons, whereas new social interactions may cause the selective death of neurons. Subsequent experiments have demonstrated that the main effect of repeated sexual interactions is to reduce adult neurogenesis in the hippocampus, bringing into question the functional role of these new neurons in social memory formation.

  • Spritzer, M.D., A. Weinberg, V. Viau and L.A.M. Galea. 2009. Prior sexual experience increases hippocampal cell proliferation and decreases risk assessment behavior in response to acute predator odor stress in the male rat. Behavioural Brain Research, 200: 106-112, doi: 10.1016/j.bbr.2009.01.003.
  • Shulman, L.M.*, M.D. Spritzer. 2014. Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females. Physiology and Behavior, 133: 8-13, doi: 10.1016/j.physbeh.2014.05.001.
  • Spritzer, M.D., M.G. Curtis*, J.P. DeLoach*, J. Maher*, and L.M. Shulman*. 2016. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats. Neuroscience, 318: 143-156, doi: 1016/j.neuroscience.2016.01.015.
  • Spritzer, M.D., K.T. Grafmiller*, S.M. Engelman*. 2013. Effects of sexual interactions on neurogenesis in the dentate gyrus of adult male rats. Society for Neuroscience Annual Meeting. San Diego, CA.

Sex differences in spatial memory among wild meadow voles—A male advantage on spatial memory tasks is well established for humans and rodents. One theory for the evolutionary cause of this sex difference is that males with better spatial memory are better able to acquire mates (sexual selection hypothesis). Professor Spritzer’s graduate research tested this hypothesis using a wild population of meadow voles. He demonstrated that male voles with better spatial memory, as assessed in a maze task, had larger home ranges and were better able to locate female voles in the field. Males with better spatial memory were also preferred by female voles as mates. We additionally demonstrated that more aggressive males did not achieve greater reproductive success, although spatial ability and aggression were positively correlated among males. Thus, there may be trade-offs between being highly aggressive and having superior spatial memory among voles. This work remains one of the few experimental tests of the sexual selection hypothesis for sex differences in spatial ability. More recently, we have explored the role of cellular turn-over in the hippocampus as a possible mechanism for individual differences in spatial memory among wild-caught voles. We have shown that there are seasonal changes in markers of neurogenesis among voles and that hippocampal cell proliferation is positively correlated home range size among male voles. This is one of the few studies to demonstrate a functional relationship between adult neurogenesis and cognition in a natural population of rodents.

  • Spritzer, M.D.,B. Meikle and N.G. Solomon. 2004. The relationship between dominance and spatial ability among male meadow voles. Journal of Comparative Psychology, 118: 332-336, doi: 10.1037/0735-7036.118.3.332.
  • Spritzer, M.D.,B. Meikle and N.G. Solomon. 2005. Female choice based on male spatial ability and aggressiveness among meadow voles. Animal Behaviour, 69: 1121-1130, doi: 10.1016/j.anbehav.2004.06.033.
  • Spritzer, M.D.,G. Solomon and D.B. Meikle. 2005. Influence of scramble competition for mates upon the spatial ability of male meadow voles. Animal Behaviour, 69: 425-436, doi: 10.1016/j.anbehav.2004.03.015.
  • Spritzer, M.D., A.W. Panning*, S.M. Engelman*, W.T. Prince*, A.E. Casler*, J.E. Georgakas*, E.C.B. Jaeger*, L.R. Nelson*, E.A. Roy*, and B.A. Wagner*. 2017. Seasonal and sex differences in cell proliferation, neurogenesis, and cell death within the dentate gyrus of adult wild-caught meadow voles. Neuroscience, 360: 155-165, doi: 10.1016/j.neuroscience.2017.07.046.