Areas of Research
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.
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.
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, with the ultimate goal of understanding 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.
We use a variety of techniques and tools: