Kathrin Engisch, Ph.D. Associate Professor Address: 012 Math & Microbiology Phone: (937) 775-2292 E-mail: kathrin.engisch@wright.edu

Research Interests:

Our laboratory uses highly specialized electrophysiological measurements in combination with genetic manipulations of individual synaptic proteins, to study the basic mechanisms of neurotransmitter release and its modulation. Neurotransmitter release shows dramatic activity-dependent behaviors. Rapid repetitive stimulation can cause an increase in release, called facilitation, in some nerve terminals. In others, the same protocol can cause depression, or a decrease in release. These types of short-term plasticity are essential for information processing in the brain, but the underlying mechanisms are unknown. We have recently found that expressing a mutant form of the synaptic vesicle protein Rab3A in adrenal chromaffin cells can greatly increase activity-dependent depression. We are currently studying the characteristics of neurotransmitter release in a Rab3A mutant mouse. We are also interested in longer term regulation of neurotransmitter release by activity. In collaboration with Mark Rich's laboratory, we have found that block of activity causes increases in synaptic strength by increasing the number of vesicles that fuse, and the size of the individual release events. We are currently examining the role of particular synaptic proteins in this long term plasticity.

In the laboratory, we study neurotransmitter release in two very accessible, simple preparations. At the mammalian nerve-muscle synapse, we use two electrode voltage clamps to record acetylcholine-activated currents in individual muscle fibers. In a neuroendocrine cell from the adrenal gland, we use perforated patch clamp to record tiny increases in the cell capacitance that occur when vesicle membrane adds to the plasma membrane surface area. We also use carbon fibers to detect released norepinephrine and epinephrine from individual adrenal chromaffin cells. These data are supplemented by imaging of intracellular calcium levels using fluorescent calcium-sensitive dyes.

See also: Molecular Regulation of Release

Selected Publications:

Engisch KL, Chernevskaya NI, Nowycky MC (1997) Short-term changes in the Ca2+- exocytosis relationship during repetitive pulse protocols in bovine adrenal chromaffin cells. J Neurosci 17:9020-9025.

Engisch KL, Nowycky MC (1996) Calcium dependence of large dense-cored vesicle exocytosis evoked by calcium influx in bovine adrenal chromaffin cells. J Neurosci 16:1359-01369.

Engisch KL, Nowycky MC (1998) Compensatory and excess retrieval: two types of endocytosis following single step depolarizations in bovine adrenal chromaffin cells. J Physiol (London) 506:608.

Engisch KL, Rich MM, Cook N, Nowycky MC (1999a) Lambert-Eaton antibodies inhibit Ca2+ currents but paradoxically increase exocytosis during stimulus trains in bovine adrenal chromaffin Cells. J Neurosci 19:3384-3395.

Engisch KL, Rich MM, Cook N, Nowycky MC (1999b) Lambert-Eaton antibodies promote activity-dependent enhancement of exocytosis in bovine adrenal chromaffin cells. Ann N Y Acad Sci 868:213-216.

Engisch KL, Wagner JJ, Alger BE (1996) Whole-cell voltage-clamp investigation of the role of PKC in muscarinic inhibition of IAHP in rat CA1 hippocampal neurons. Hippocampus 6:183-191.

Thiagarajan R, Tewolde T, Li Y, Becker PL, Rich MM, Engisch KL (2004) Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells. J Physiol 555:439-457.

Thiagarajan R, Wilhelm J, Tewolde T, Li Y, Rich MM, Engisch KL (2005) Enhancement of asynchronous and train-evoked exocytosis in bovine adrenal chromaffin cells infected with a replication deficient adenovirus, J Neurophysiol 94:3278-3291.

Wang X, Engisch KL, Li Y, Pinter MJ, Cope TC, Rich MM (2004) Decreased synaptic activity shifts the calcium dependence of release at the mammalian neuromuscular junction in vivo. J Neurosci 24:10687-10692.

Wang X, Li Y, Engisch KL, Nakanishi ST, Dodson SE, Miller GW, Cope TC, Pinter MJ, Rich MM (2005) Activity-dependent presynaptic regulation of quantl size at the mammalian neuromuscular junction in vivo. J Neurosci 25:343-351.