Current Research Projects
Ovarian Hormone Control of Threat Memory Processes
Women are twice as likely as men to experience post-traumatic stress disorder (PTSD), and clinical research implicates cycling ovarian hormones as a primary mechanism driving this sex difference in susceptibility. Estradiol levels at the time of trauma are inversely correlated with subsequent development of PTSD, and the mid-cycle estradiol surge coincides with less severe PTSD symptoms. We are interested in understanding how ovarian hormones can influence the fundamental processes of threat memory in naturally cycling mice. We investigate how peaks and troughs in cycling ovarian hormones induce unique neural states that influence the acquisition, recall, and behavioral responses of conditioned threat memory. Several years of federally-funded research have led us to discover not only that threat memory processes are regulated in a state-dependent manner across the estrous cycle but also a specific cellular population within the lateral septum driving this phenomenon. Our current work seeks to understand the molecular mechanisms driving recruitment of this cellular population with the long-term goal of developing therapeutics that influence this circuit to suppress threat memory.
Estradiol Regulation of Valence Processing in the Basolateral Amygdala
In addition to PTSD, women are also twice as likely as men to experience other stress-related disorders, such as anxiety and major depressive disorders. A common link between these psychiatric illnesses is dysregulation of valence processing, which refers to the intrinsic positive or negative emotional value we assign to external stimuli. In both humans and rodent models, valence processing is regulated across the female reproductive cycle whereby high physiological levels of estradiol reduce negative and promote positive valence. The amygdala is well-established as the valence processing center of the brain, and this federally-funded project seeks to establish novel cellular mechanisms driving this beneficial effect of estradiol, with a focus on amygdala neurons that express estrogen receptor beta. We hypothesize that estradiol suppresses amygdala neurons coding negative valence to promote resilience to stress. Our long-term goal is to develop therapeutics downstream of estradiol signaling as potential targets for the treatment of stress-related disorders.
Novel Roles of Glp-1 in Female Cognitive and Cardiometabolic Aging
Ovarian hormone depletion following menopause leads to a unique aging trajectory in women compared to men, including increased risk of obesity, diabetes, cardiometabolic dysfunction, cognitive decline, and dementia. Glucagon-like peptide-1 (Glp-1) agonists, such as semaglutide, have emerged to be promising treatments for not only for diabetes and obesity but also age-related cognitive decline and dementia. In both humans and preclinical rodent models, circulating levels of Glp-1 decline after reproductive senescence and can be rescued by estradiol replacement. In collaboration with Dr. Andrew Hardaway’s lab, we are investigating the mechanisms by which estradiol regulates central and peripheral Glp-1 levels to influence consummatory behavior, cardiometabolic function, and cognitive processes across aging and in menopause models. This project has been led by lab undergraduate students and funded by UAB’s O’Brien Center.
Publications
(2026) The lateral septum orchestrates state-dependent modulation of associative threat memory dynamics across the ovarian hormone cycle. Baumgartner, N.E., Teravskis, P.J., Dechachutinan, N.S., Adcock Binion, K.A., Bell, G.C., Dasari, A.S., Newberry, G.C., Penumudi, M., Rumbell, T.H., & Lucas, E.K. | bioRxiv. PDF
(2025) Dietary phytoestrogens recalibrate socioemotional behavior in C57Bl/6J mice in a sex- and timing-dependent manner. Le Roux, C.E., Farthing, A.L., & Lucas, E.K. | Hormones and Behavior, 168: 105678. PDF
(2023) Sex differences in avoidance behavior and cued threat memory dynamics in mice: Interactions between estrous cycle and genetic background. Ryherd, G.L, Bunce, A.L., Edwards, H.A., Baumgartner, N.E., & Lucas, E.K. | Hormones and Behavior, 156: 105439-47. PDF
(2023) Moving beyond descriptive nosology: an argument for negative valence systems disorder. Lucas, E.K. & McCullumsmith, R.E. | Neuropsychopharmacology, 49: 323-324. PDF
(2023) Sex differences in socioemotional behavior and changes in ventral hippocampal transcription across aging in C57Bl/6J mice. Baumgartner, N.E., Biraud, M.C., & Lucas, E.K. | Neurobiology of Aging, 130: 141-143. PDF
(2022) Sex-Specific Neural Networks of Cued Threat Conditioning: A Pilot Study. du Plessis, K.C., Basu, S., Rumbell, T.H., & Lucas, E.K. | Frontiers in Systems Neuroscience, Special Issue on Negative Valence Systems, 16: 1-11. PDF
(2020) Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice. Flanigan, M.E., Aleyasin, H., Li, L., Burnett, C.J., Chan, K.L., LeClair, K.B., Lucas, E.K., Matikainen-Ankney, B., Cuttoli, R.D., Takahashi, A., Menard, C., Pfau, M.L., Golden, S.A., Bouchard, S., Calipari, E.S., Nestler, E.J., DiLeone, R.J., Yamanaka, A., Huntley, G.W., Clem, R.L., & Russo, S.J. | Nature Neuroscience, 23: 638-650. PDF
(2020) Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior. Bicks, L.K., Yamamuro, K., Flanigan, M.E., Kim, J.M., Kato, D., Lucas, E.K., Koike, H., Peng, M.S., Brady, D.M., Chandrasekaran, S., Norman, K.J., Smith, M.R., Clem, R.L., Russo, S.J., Akbarian, S., & Morishita, H. | Nature Communications, 11: 1003. PDF
(2018) Prazosin during fear conditioning facilitates subsequent extinction in male C57Bl/6N mice. Lucas, E.K., Wu, W-C., Roman-Ortiz, C., & Clem, R.L. | Psychopharmacology, Special Issue, Psychopharmacology of Extinction, 236: 273-279. PDF
(2017) GABAergic interneurons: the orchestra or the conductor in fear learning and memory? Lucas, E.K. & Clem, R.L. | Brain Research Bulletin, Special Issue, Memory Mechanisms in Health and Disease, 141: 13-19. PDF
(2016) Multimodal and site-specific plasticity of amygdala parvalbumin interneurons after fear learning. Lucas, E.K., Jegarl, A.M., Morishita, H., & Clem, R.L. | Neuron, 91, 3: 629-643. PDF
(2016) Cortical PGC-1α-dependent transcripts are reduced in postmortem tissue from patients with schizophrenia. McMeekin, L.J., Lucas, E.K., Meador-Woodruff, J.H., McCullumsmith, R.E., Hendrickson, R.C., Gamble, K.L., & Cowell, R.M. | Schizophrenia Bulletin, 42, 4: 1009-1017. PDF
(2015) Interneuron transcriptional dysregulation causes frequency-dependent alterations in the balance of inhibition and excitation in hippocampus. Bartley, A.F., Lucas, E.K., Brady, L.J., Li, Q., Hablitz, J.J., Cowell, R.M., & Dobrunz, L.E. | Journal of Neuroscience, 35, 46: 15276-15290. PDF
(2015) Cerebellar transcriptional alterations with Purkinje cell dysfunction and loss in mice lacking PGC-1α. Lucas, E.K., Reid, C.S., McMeekin, L.J., Dougherty, S.E., & Cowell, R.M. | Frontiers in Cellular Neuroscience, Special Issue, Neurodegeneration: from Genetics to Molecules, 8, 441: 1-13. PDF
(2014) PGC-1α provides a transcriptional framework for synchronous neurotransmitter release from parvalbumin-positive interneurons. Lucas, E.K., Dougherty, S.E., McMeekin, L.J., Reid, C.S., West, A.B., Dobrunz, L.E., Hablitz, J.J., & Cowell, R.M. | Journal of Neuroscience, 34, 43: 14375-14387. PDF
(2014) Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes. Lucas, E.K., Jegarl, A., & Clem, R.L. | Behavioural Brain Research, 274: 219-225. PDF
(2014) Mice lacking the transcriptional coactivator PGC-1α exhibit alterations in inhibitory synaptic transmission in the motor cortex. Dougherty, S.E., Bartley, A.F., Lucas, E.K., Dobrunz, L.E., Hablitz, J.J., & Cowell, R.M. | Neuroscience, 271: 137-148. PDF
(2013) Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia. Shan, D., Lucas, E.K., Drummond, J.B., Haroutunian, V., Meador-Woodruff, J.H., & McCullumsmith, R.E. | Schizophrenia Research, 144 (1-3): 1-8. PDF
(2012) Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking PGC-1α. Lucas, E.K., Dougherty, S.E., Trinh, A.T., Reid, C.S., McMeekin, L.J., & Cowell, R.M. | PLoS ONE, 7, 8: e42878. PDF
(2012) Disruption of Purkinje cell function prior to huntingtin accumulation and cell loss in an animal model of Huntington Disease. Dougherty, S.E., Reeves, J. L., Lucas, E. K., Gamble, K. L., Lesort, M., & Cowell, R.M. | Experimental Neurology, 236: 171-178. PDF
(2010) Neuronal inactivation of PPARγ coactivator 1α (PGC-1α) protects mice from diet-induced obesity and leads to degenerative lesions. Ma, D., Li, S., Lucas, E.K., Cowell, R.M., & Lin, J.D. | Journal of Biological Chemistry, 285, 10: 39087-39095. PDF
(2010) Parvalbumin deficiency and GABAergic dysfunction in mice lacking PGC-1α. Lucas, E.K., Markwardt, S.J., Gupta, S., Meador-Woodruff, J.H., Lin, J.D., Overstreet-Wadiche, L., & Cowell, R.M. | Journal of Neuroscience, 30, 21: 7227-7235. PDF
(2009) Do perceptually salient stimuli reduce children’s risky decisions? Schwebel, D.C., Lucas, E.K., & Pearson, A. | Journal of Clinical Psychology in Medical Settings, 16, 3: 223-232. PDF
(2007) Unintentional injury risk in children with externalizing behavior disorders at summer camp. Schwebel, D. C., Tavares, C. L., Lucas, E. K., Bowling, E. B., & Hodgens, J. B. | Journal of Clinical Psychology in Medical Settings 14, 2: 145-151. PDF
