Joseph F. Margiotta, Ph.D.
听
Professor Emeritus
Email:听 joseph.margiotta@utoledo.edu
Education:
1970: BS,听Fordham University, Bronx , NY PhD
1980: Ph.D., State University of New York , Stony Brook , NY
Research Interest:
Our experiments focus on chemical synapses, the functional units of cell-to-cell communication
in the nervous system. At nicotinic synapses, acetylcholine (ACh) released from presynaptic
nerve terminals, activates nicotinic acetylcholine receptors (nAChRs) on adjacent
postsynaptic target neurons. Such synapses underlie fast excitatory transmission in
all autonomic ganglia, making them essential for maintaining visceral functions that
sustain life. nAChRs and by extension nicotinic synapses are also targeted in numerous
neurological illnesses inclulding Alzheimer鈥檚 and Parkinson鈥檚 disease, with an annual
health cost of $187 billion. Moreover, chronic nicotine exposure from tobacco smoke
perturbs nAChRs and nicotinic synapses, reinforcing nicotine addiction and underlying
smoking-related illnesses that yearly kill 438,000 Americans and result in $167 billion
in economic losses. Despite this relevance to health and disease, little is known
about mechanisms regulating the function, plasticity and formation of nicotinic synapses.
We address this issue by examining the utilization and regulation of nAChR subtypes
at synapses, the roles of activity, neuropeptides and growth factors in regulating
nicotinic synapse formation and function, and the molecular mechanisms underlying
pre-and postsynaptic differentiation.
Research Techniques:
Our studies utilize multiple experimental approaches, including whole-cell and single-channel
recording, cloning and expression of neural genes, signal pathway biochemistry, and
cell imaging.
Research Summary:
The references cited below provide an introduction to our current work, much of which
is directed towards understanding how neurotrophins and neuropeptides, such as BDNF
and PACAP, regulate nicotinic synaptic function. Here, we recently found that BDNF
and PACAP enhance transmission at nicotinic synapses, and hypothesize they do so via high-affinity cognate receptors (TrkB and PAC 1R, respectively), each triggering
effector systems that differentially regulate the function, structure and formation
of nicotinic synapses.
To access individual synaptic components, methods were devised to evoke and record
excitatory postsynaptic currents (EPSCs) at single nicotinic synapses (Fig. 1).
To control synaptic responses, transfection methods have been developed to ectopically express variant TrkB, PAC 1R nAChR, and toxin genes in single neurons (e.g. Fig. 2).
Using these new approaches we are elucidating how BDNF and PACAP exert rapid and sustained
actions on nicotinic synapses, and determining how the resultant signals influence
nicotinic synaptogenesis. The findings are expected to uncover mechanisms that normally
regulate nicotinic synapses, and that may underlie processes causing synaptic impairment
in neurological illnesses, developmental disorders, and nicotine addiction.
Selected References:
Burns AL, D Benson, MJ Howard, and JF Margiotta (1997). Chick ciliary ganglion neurons contain transcripts coding for AChR associated
protein at synapses (rapsyn). Journal of Neuroscience. 17: 5016-5026.
Pardi D and JF Margiotta (1999). PACAP activates a PLC-dependent signal pathway in chick ciliary ganglion neurons that selectively inhibits a 7-containing nicotinic receptors. Journal of Neuroscience. 19: 6327-6337.
Pugh PC and JF Margiotta (2000). Nicotinic acetylcholine receptor agonists promote survival and reduce apoptosis of chick ciliary ganglion neurons. Molecular and Cellular Neuroscience. 15: 113-122.
McNerney ME, D Pardi, PC Pugh, Q Nai, and JF Margiotta (2000). Expression and channel properties of -bungarotoxin-sensitive acetylcholine receptors on chick ciliary and choroid neurons. Journal of Neurophysiology. 84: 1314-1329.
听 (Cover article).