John T. Hackett, Ph.D., Professor
and Biological Physics
University of Virginia
PO Box 800736
Charlottesville, VA 22908-0736
Neurosecretion of transmitter substances is a cellular process whereby information transfer occurs in the nervous system. Thus, normal nervous system signaling and resultant behavior depend upon an orderly and closely regulated release mechanism for these transmitters. The hypothesis we wish to test is that the quantal processes of docking and fusion of neurotransmitter packets are critical sites which can be modulated by synaptic integration.
The physiological measures of quantal docking and fusion may be related to the presynaptic parameters (n) and (p), respectively. However, a comprehensive model relating these parameters to modulation of neurosecretion has not been forthcoming. To further work in this area, we have developed a computer algorithm for high resolution quantal detection and for an analysis of unbiased presynaptic parameters.
In concert with these improvements we have found that the increased efficacy of neurosecretion elicited by repetitive simulation of the lobster neuromuscular junction can be explained in terms of changes in presynaptic parameters. This explanation also includes provision for the replenishment of released quanta from a depot pool and mobilization of extra quanta to docking sites.
We wish to further explore presynaptic inhibition and other modes of enhanced neurosecretion, augmentation and potentiation, which may be the forerunners of long term memory storage. Thus, we propose that the isolation of docking and fusion steps by evaluating presynaptic parameters will reveal the mechanisms of synaptic plasticity.
Positive feedback loops sustain repeating bursts in neuronal circuits. Friesen WO, Mullins OJ, Xiao R and Hackett JT.. Journal of Biological Physics 2010 Dec. 15
Neuronal control of swimming behavior: comparison of vertebrate and invertebrate model systems.Mullins OJ, Hackett JT, Buchanan JT, Friesen WO. Prog Neurobiol. 2011 Feb;93(2):244-69. Epub 2010 Nov 18. PMCID: PMC3034781
Local-distributed integration by a novel neuron ensures rapid initiation of animal locomotion.Mullins OJ, Hackett JT, Friesen WO. J Neurophysiol. 2011 Jan;105(1):130-44. Epub 2010 Oct 27. PMID:20980540
Mechnisms underlying different facilitation forms at the lobster neuromuscular synapse.Bykhovskaia M, Polagaeva E, Hackett JT. Brain Res. 2004 Sep 3;1019(1-2):10-21.PMID:15306233
Regulation of the neuronal nicotinic acetylcholine receptor by SRC family tyrosine kinases. Wang K, Hackett JT, Cox ME, Van Hoek M, Lindstrom JM, Parsons SJ. J Biol Chem. 2004 Mar 5;279(10):8779-86. Epub 2003 Dec 16. PMID:14679211
Statistical analysis of quantal events in synaptic transmission in the neuromuscular junction in lobster Homarus americanus. Vorob'eva ON, Polagaeva EB, Worden MK, Hackett JT, Bykhovskaia MB.Zh Evol Biokhim Fiziol. 2002 Jul-Aug;38(4):341-7. Russian. No abstract available. PMID: 12244680
Effect of Ca 2+ on presynaptic facilitation.Bykhovskaia, M., Polagaeva, E and. Hackett, JT. (2002) Neuorcomputing 44-46: 1-5
Hyperosmolarity reduces facilitation by a Ca(2+)-independent mechanism at the lobster neuromuscular junction: possible depletion of the releasable pool. Bykhovskaia M, Polagaeva E, Hackett JT. J Physiol. 2001 Nov 15;537(Pt 1):179-90. PMCID: PMC2278922
Stochastic modeling of facilitated neurosecretion. Bykhovskaia M, Worden MK, Hackett JT.
J Comput Neurosci. 2000 Mar-Apr;8(2):113-26. PMID: 10798597
Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method. Vorobieva ON, Hackett JT, Worden MK, Bykhovskaia M.J Neurosci Methods. 1999 Oct 15;92(1-2):91-9. PMID:10595707
Asynchrony of quantal events in evoked multiquantal responses indicates presynaptic quantal interaction. Bykhovskaia M, Hackett JT, Worden MK. J Neurophysiol. 1999 May;81(5):2234-42.PMID:10322062
Presynaptic Facilitation: Quantal Analylsis and Simulations. Bykhovskaia, M., Worden, M.K., and. Hackett, J.T (1999). Neurocomputing 26-27: 9-15.
Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method. Vorobieva, O.N., Hackett J. T., Worden, M.K. and Bykhovskaia, M (1999) J. Neurosci. Methods 92: 91-99PMID: 10595707
Facilitation at the lobster neuromuscular junction: a stimulus-dependent mobilization model. Worden MK, Bykhovskaia M, Hackett JT. J Neurophysiol. 1997 Jul;78(1):417-28. PMID:9242290
An algorithm for high-resolution detection of postsynaptic quantal events in extracellular records. Bykhovskaia M, Worden MK, Hackett JT. J Neurosci Methods. 1996 Apr;65(2):173-82. PMID: 8740595
Ca(2+)-independent and Ca(2+)-dependent stimulation of quantal neurosecretion in avian ciliary ganglion neurons. Brosius DC, Hackett JT, Tuttle JB. J Neurophysiol. 1992 Oct;68(4):1229-34. PMID:1432080
Xenopus oocyte K+ current. II. Adenylyl cyclase-linked receptors on follicle cells. Greenfield LJ Jr, Hackett JT, Linden J. Am J Physiol. 1990 Nov;259(5 Pt 1):C784-91. PMID:2173413
Xenopus oocyte K+ current. I. FSH and adenosine stimulate follicle cell-dependent currents. Greenfield LJ Jr, Hackett JT, Linden J. Am J Physiol. 1990 Nov;259(5 Pt 1):C775-83. PMID:2122736