Catherine A Christian

Research in my laboratory is focused on synaptic transmission, cellular excitability, neuromodulation, and circuit plasticity in the contexts of neuroendocrinology and epilepsy. We are taking a multidisciplinary approach by using several techniques such as patch clamp electrophysiology, optogenetics, electroencephalography (EEG), ultraviolet uncaging, and calcium imaging to explore the following research themes:

1) Mechanisms of co-morbidity of neuroendocrine dysfunction and epilepsy

Many patients with epilepsy, particularly temporal lobe epilepsy, experience dysfunctional neuroendocrine regulation as a consequence of seizures and/or of taking antiepileptic drugs. This has a significant impact on overall health, quality of life, and seizure control. A greater understanding of the anatomical and functional connections between limbic and hypothalamic systems is needed in order to understand the etiology of this neuroendocrine dysfunction and to develop new treatments. We are focusing on the impact of epilepsy on the hypothalamo-pituitary-gonadal (HPG) axis, which controls the production of gonadal steroid hormones (e.g., estrogen, progesterone, and testosterone) and fertility in both males and females. Elucidating the cellular and circuit mechanisms of HPG axis dysregulation in epilepsy will further our understanding of the hormonal regulation of seizures and provide new targets for therapeutic interventions.

2) Glial-neuronal interactions

Recent exciting work indicates that glial cells (such as astrocytes) play important roles in neuronal functions, particularly with respect to regulation of synapses. Although a role for astrocytes in modulating excitatory glutamatergic transmission is well established, less is known about the roles of astrocytes in modulating synaptic inhibition. We are exploring this question by selectively altering astrocytic function and observing the changes in GABAergic transmission and circuit function that result from modifications in astrocytic activity. We are also investigating the relative roles of glia and neurons as local sources of neuromodulators and neurohormones in different areas of the brain.

3) Peptide and steroid modulation of synapses and circuits

We are currently focusing on the mechanisms of endogenous (i.e., brain-derived) modulation of GABAergic synaptic transmission, which is typically inhibitory, and the effects of this modulation on the larger circuits in which these synapses are located. Our ultimate goal is to understand how this modulation affects both normal and abnormal behaviors. Current projects are investigating the actions of endozepines, which are endogenous peptides that mimic the actions of benzodiazepine drugs, and neurosteroids, which are derived in the brain from cholesterol or hormones such as progesterone. We are also interested in the effects of neuroendocrine hormone peptides, such as gonadotropin-releasing hormone, on areas of the brain outside of the hypothalamus.

Representative Publications

Li J, Kim JS, Abejuela VA, Lamano JB, Klein NJ, Christian CA (2017) Disrupted female estrous cyclicity in the intrahippocampal kainic acid mouse model of temporal lobe epilepsy. Epilepsia Open, 2:39-47

Christian CA, Huguenard JR (2013) Astrocytes potentiate GABAergic transmission in the thalamic reticular nucleus via endozepine signaling. Proc Natl Acad Sci USA 110:20278-20283

Christian CA, Huguenard JR (2013) Sniffer Patch Laser Uncaging REsponse (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance. J Neurophysiol 110:1722-1731

Christian CA, Herbert AG, Holt RL, Peng K, Sherwood KD, Pangratz-Fuehrer S, Rudolph U, Huguenard JR (2013) Endogenous positive allosteric modulation of GABA(A) receptors by Diazepam binding inhibitor. Neuron, 78:1063-1074

Christian CA, Moenter SM (2010) The neurobiology of preovulatory and estradiol-induced gonadotropin-releasing hormone surges. Endocr Rev, 31:544-577

Christian CA, Pielecka-Fortuna J, Moenter SM (2009) Estradiol suppresses glutamatergic transmission to gonadotropin-releasing hormone neurons in a model of negative feedback in mice. Biol Reprod 80:1128-113

Christian CA, Moenter SM (2008) Critical roles for fast synaptic transmission in mediating estradiol negative and positive feedback in the neural control of ovulation. Endocrinology 149:5500-5508

Christian CA*, Glidewell-Kenney C*, Jameson JL, Moenter SM (2008) Classical estrogen receptor alpha signaling mediates negative and positive feedback on gonadotropin-releasing hormone neuron firing. Endocrinology 149:5328-5334 (*equal contribution)

Christian CA, Moenter SM (2008) Vasoactive intestinal polypeptide can excite gonadotropin-releasing hormone neurons in a manner dependent on estradiol and gated by time of day. Endocrinology 149:3130-3136

Christian CA, Moenter SM (2007) Estradiol induces diurnal shifts in GABA transmission to gonadotropin-releasing hormone neurons to provide a neural signal for ovulation. J Neurosci 27:1913-1921

Christian CA, Mobley JL, Moenter SM (2005) Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity. Proc Natl Acad Sci USA 102:15682-15687