My laboratory studies synaptic modulation in the hippocampus and cortex of the mammalian brain. Our recent work has focused on the physiologic roles of endogenous cannabinoids and nerve growth factors such as BDNF in various forms of synaptic plasticity that are important for learning and memory. These systems are currently major targets for the development of novel therapeutics for neurologic and neurodegenerative disease. Recent work from our laboratory has identified important interactions between BDNF-trkB signaling and endocannabinoid signaling. Specifically, we have shown that BDNF induces release of endocannabinoids at inhibitory synapses, and we identified complementary roles for endogenous BDNF and endocannabinoids in long-term depression at inhibitory synapses.

Another area of interest focuses on understanding the neuronal and synaptic deficits in autism spectrum disorders. In particular, we have been studying Angelman syndrome and Dup15q syndrome using induced pluripotent stem cells (iPSCs) that are derived from human skin cells and then reprogrammed and differentiated into neurons. This project involves patch clamp recordings, calcium imaging, and molecular characterization of these patient-specific brain neurons grown in culture. In collaboration with the laboratories of Dr. Stormy Chamberlain and Dr. Les Loew, we are interested in comparing the functional and structural properties of synapses and neuronal circuits from patients with Angelman syndrome or Dup15q syndrome compared to unaffected control subjects.

Work that began during my postdoctoral fellowship and continued in my own laboratory were some of the first studies showing rapid BDNF modulation of synaptic transmission in the hippocampus. We went on to produce a detailed characterization of the pre- and postsynaptic effects of BDNF, including regulation of NMDA receptor signaling.

We were also the first to characterize the role of endogenous cannabinoid signaling in the neocortex. This included novel discoveries of cortical laminar specificity in the effects of CB1 receptor activation and endocannabinoid modulation of dendritic back-propagating action potentials.

Recent work has identified important interactions between BDNF-trkB signaling and endocannabinoid signaling. Specifically, we have shown that BDNF induces release of endocannabinoids at inhibitory synapses, and we identifed complementary roles for endogenous BDNF and endocannabinoids in long-term depression at inhibitory synapses.

We are currently using cortical neurons differentiated from patient-specific induced pluripotent stem cells to examine the cellular and synaptic pathophysiology in Angelman syndrome and Dup15q syndrome. We are also using this stem cell approach to examine genetic risk factors related to alcohol use disorders.

Not Accepting Lab Rotation Students at this time

One potential rotation project is to examine the interaction between cannabinoids and nerve growth factors in the rodent neocortex. Specifically, this project will introduce the student to patch clamp recording techniques, intracellular calcium imaging, and RNA interference methods in brain slices to determine how cannabinoids regulate growth factor production and explore the functional relevance of this interaction at cortical synapses.

Another project involves recording the electrical activity and monitoring intracellular calcium dynamics from human stem cell-derived brain neurons grown in culture. We are interested in characterizing the functional properties, protein expression patterns, and synaptic connections from neurons derived from patients with autism and other neurogenetic disorders and identifying underlying deficits that may be related to disease phenotype.

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