- I am a synaptic neurophysiologist with experience with path clamp electrophysiology in cell culture and in retinal sl... moreI am a synaptic neurophysiologist with experience with path clamp electrophysiology in cell culture and in retinal slices. During my doctoral work with Dr. Steven Mennerick, I explored how two drugs (memantine and ketamine) elicit strikingly different clinical profiles despite similar pharmacological actions at their targeted receptor (NMDA receptors). My work uncovered an unexplored effect of low gating efficacy of the NMDA receptor on pharmacological profiles of clinically used drugs. I am now pursuing a postdoctoral fellowship in the lab of Dr. Peter Lukasiewicz. My research in this lab is to explore the role of retinal dopamine in visual adaptation.edit
Research Interests:
It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavior such... more
It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavior such as seizures. However, methods for quantifying bursting and synchrony are not agreed upon and can be confounded with spike rate measures. Previous validation has largely relied on in silico networks and single experimental conditions. How published measures of bursting and synchrony perform when applied to biological networks of varied average spike rate and subjected to varied experimental challenges is unclear. In multielectrode array recordings of network activity, we found that two mechanistically distinct drugs, cyclothiazide and bicuculline, produced equivalent increases in average spike rate but differed in bursting and synchrony. We applied several measures of bursting to the recordings (2 threshold interval methods and a surprise-based method) and found that a measure based on an average critical interval, adjusted for the array-wide spike rate, performed best in quantifying differential drug effects. To quantify synchrony, we compared a coefficient of variation-based measure, the recently proposed spike time tiling coefficient, the SPIKE-distance measure, and a global synchrony index. The spike time tiling coefficient, the SPIKE-distance measure, and the global synchrony index all captured a difference between drugs with the best performance exhibited by the global synchrony index. In summary, our exploration should aid other investigators by highlighting strengths and limitations of current methods.
Research Interests:
Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important... more
Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how positive allosteric modulators (PAMs) might affect the pharmacodynamics of these NMDA blockers. We used two different PAMs: SGE-201, an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with pregnenolone sulphate (PS), to test on memantine and ketamine responses in single cells (oocytes and cultured neurons) and networks (hippocampal slices), using standard electrophysiological techniques. SGE-201 and PS had no effect on steady-state block or voltage dependence of a channel blocker. However, both PAMs increased the actions of memantine and ketamine on phasic excitatory post-synaptic currents, but neither revealed underlying pharmacodynamic differences. SGE-201 accelerated t...
Research Interests:
The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that... more
The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.
ABSTRACT Transition voltage spectroscopy was used to measure the charge injection properties of monolayers of bithiophene phosphonate, quarterthiophene phosphonate, and decylphosphonate covalently bonded to an indium tin oxide surface.... more
ABSTRACT Transition voltage spectroscopy was used to measure the charge injection properties of monolayers of bithiophene phosphonate, quarterthiophene phosphonate, and decylphosphonate covalently bonded to an indium tin oxide surface. Hysteresis was observed for all three phosphonates, which is possibly explained by charge retention at the phosphonate−ITO interface. Unlike previous work on thiolate-based molecular junctions, there is no significant difference between the charge injection barriers of the three phosphonates, suggesting that the phosphonate moiety dominates the observed charge injection properties.