Current Research Projects
Sex-Specific Brain Circuits for Emotional Memory
The emotion of fear is a powerful trigger for memory storage, helping us avoid cues associated with dangerous outcomes. However, fear memories become maladaptive in common psychiatric diseases disproportionately experienced by women, such as post-traumatic stress disorder, generalized anxiety disorder, panic disorder, and phobia. By understanding how females encode and express fear memories differently than males, we will be able to uncover sex-specific mechanisms and treatment strategies for fear-based psychiatric disease. We use a variety of techniques to pinpoint specific brain circuits and neuron subtypes underlying fear memory dynamics, including whole-brain mapping, in vivo calcium imaging, electrophysiology, and single cell RNA sequencing. We then establish causal relationships between these observations and maladaptive emotional responses by activating and silencing these pathways with chemogenetic or optogenetic tools. Our long-term goal is to discover novel brain circuits driving conditioned fear behavior in females.
ovarian hormone regulation of neuronal plasticity & behavior
Epidemiological data show that women are most susceptible to affective spectrum disorders during reproductive viability: before puberty or after menopause, the prevalence of these disorders between the sexes is equivalent. This clinical reality suggests that puberty onset and circulating sex hormones confer women’s susceptibility to such disorders. Our lab employs a lifespan approach to investigate how gonadal hormones orchestrate brain function and behavior by focusing on puberty onset in adolescent mice, estrous cycle in adult mice, and reproductive senescence in aged mice. We are particularly interested in (1) the anxiolytic actions of ovarian hormones in naturally cycling females, (2) mechanisms driving socioemotional behavioral changes during hormonal transitions, and (3) how stress during puberty may permanently re-wire the brain the promote susceptibility to affective disorders. We use a combination of genetic, electrophysiological, and pharmacological tools to tackle these questions.
Publications
(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, In Press. PDF
(2023) Moving beyond descriptive nosology: an argument for negative valence systems disorder. Lucas, E.K. & McCullumsmith, R.E. | Neuropsychopharmacology, In Press. 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
