John T. Hackett

Primary Appointment

  • Professor, Molecular Physiology and Biological Physics

Contact

Research Interest(s)

Synaptic Transmission

Research Description

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.

Selected Publications

  • Friesen W, Mullins O, Xiao R, Hackett J. Positive feedback loops sustain repeating bursts in neuronal circuits. Journal of biological physics. 2012;37(3): 317-45. PMID: 22654180 | PMCID: PMC3101330
  • Mullins O, Brodfuehrer P, Jusufovińá S, Hackett J, Friesen W. Specialized brain regions and sensory inputs that control locomotion in leeches. Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology. 2011;198(2): 97-108. PMID: 22037913 | PMCID: PMC3265633
  • Mullins O, Hackett J, Buchanan J, Friesen W. Neuronal control of swimming behavior: comparison of vertebrate and invertebrate model systems. Progress in neurobiology. 2010;93(2): 244-69. PMID: 21093529 | PMCID: PMC3034781
  • Mullins O, Hackett J, Friesen W. Local-distributed integration by a novel neuron ensures rapid initiation of animal locomotion. Journal of neurophysiology. 2010;105(1): 130-44. PMID: 20980540
  • Bykhovskaia M, Polagaeva E, Hackett J. Mechnisms underlying different facilitation forms at the lobster neuromuscular synapse. Brain research. 2004;1019(1): 10-21. PMID: 15306233
  • Wang K, Hackett J, Cox M, Van Hoek M, Lindstrom J, Parsons S. Regulation of the neuronal nicotinic acetylcholine receptor by SRC family tyrosine kinases. The Journal of biological chemistry. 2003;279(10): 8779-86. PMID: 14679211
  • Vorob'eva O, Polagaeva E, Worden M, Hackett J, Bykhovskaia M. [Statistical analysis of quantal events in synaptic transmission in the neuromuscular junction in lobster Homarus americanus]. Zhurnal evoliutsionnoń≠ biokhimii i fiziologii. 2002;38(4): 341-7. PMID: 12244680
  • Bykhovskaia M, Polagaeva E, Hackett J. Hyperosmolarity reduces facilitation by a Ca(2+)-independent mechanism at the lobster neuromuscular junction: possible depletion of the releasable pool. The Journal of physiology. 2001;537 179-90. PMID: 11711571 | PMCID: PMC2278922