Mary Kate Worden, Ph.D.

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Mary Kate Worden, Ph.D.

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Associate Professor of Medical Education

The research interests of my lab focus on the fundamental biological problems of vesicle mobilization and membrane fusion. In the nervous system, where the strength of the neurosecretory process is critical for learning and memory, synaptic vesicle mobilization and fusion are regulated in dynamic ways. We are studying neurosecretion at the crusteacean neuromuscular junction, where synaptic output is exquisitely regulated both by the frequency of electrical activity in the motoneuron and by the modulatory effects of circulating neurohormones. At this synapse, the number of synaptic vesicles that undergo exocytosis in response to a single action potential is a steep function of the stimulus frequency. This phenomenon is called frequency facilitation, and is a form of short-term synaptic plasticity. By electrophysiologically measuring synaptic output from a small number of release sites during frequency facilitation, we have developed a quantitative model that describes synaptic transmission in terms of the mobilization of synaptic vesicles to dock at release sites (Worden et al., 1997).

WordenFig1

Figure 1: Schematic diagram illustrating the physiological processes determining the number of docked quanta (n). Quanta are mobilized from a reserve store (S) by biochemical processes (arrows) that mobilize or demobilize quanta from docking sites with rate constants K-m and K-d respectively. In the absence of stimulation, quanta have a low probability (P-o) of fusing with the presynaptic terminal membrane. When the neuron is stimulated at frequency f, a number of quanta (N-s) become docked in response to each action potential and quanta undergo fusion with a higher probability p. From Worden et al., (1997).

The utility of the stimulus-dependent mobilization model is that it enables estimation of the number of quantal units of transmitter mobilized by each action potential, as well as the rate constant of quantal demobilization from the docking sites back to the reserve quantal store. One current line of research focuses on the cellular mechanisms by which circulating hormones, such as serotonin, potentiate neurotransmission. We are testing the hypothesis that serotonin either enhances quantal mobilization or decreases quantal demobilization, in addition to increasing the probability of quantal fusion. Future plans include examining how second messenger pathways regulate the processes of quantal mobilization and docking, and identifying the physiological roles played by synaptic proteins in the neurosecretory process.

 

Representative Publications:

Worden, M.K., Kravitz, E.A., Goy, M.F. (1995) Peptide F1, an N-terminally extended analogue of FMRFamide, enhances contractile activity in multiple target tissues in lobster. J. Experimental Biology 198:93-108.
Bykhovskaia, M., Worden, M.K., Hackett, J.T. (1996) An algorithm for high resolution detection of postsynaptic quantal events in extracellular records. J. Neuroscience Methods 65:173-182.
Worden, M.K., Bykhovskaia, M., Hackett, J.T. (1997) Facilitation at the lobster neuromuscular junction: a stimulus-dependent mobilization model. J. Neurophysiology 78:417-428.
Worden, M.K . (1998) Modulation of vertebrate and invertebrate neuromuscular junctions. Current Opinion in Neurobiology 8(6):740-745.
Bykhovskaia, M., Worden, M.K., Hackett, J.T. (1999) Presynaptic facilitation: Quantal analysis and simulations. Neurocomputing 26-27: 9-15.
Vorobieva, O.N., Hackett, J.T., Worden, M.K., Bykhovskaia, M. (1999) Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method. J. Neuroscience Methods 92:91-99.
Bykhovskaia, M., Hackett, J.T., Worden, M.K. (1999) Asynchrony of quantal events in evoked multiquantal responses indicates presynaptic quantal interaction. J. Neurophysiology 81:2234-2242.
Bykhovskaia, M., Worden, M.K., Hackett, J.T. (2000) Stochastic modeling of facilitated neurosecretion. J. Computational Neuroscience 8:113-126.

PubMed Link to Worden Publications