Laboratory project: "Cell Recognition and Synapse Formation"
Summary of work for this project as indicated on the report: "Long range objectives are to define reactions which are
required for synapse formation and for transmission of information from cell to cell."
Item is a photocopy.
Number of Image Pages:
3 (222,616 Bytes)
1976-09 (September 1976)
Nirenberg, Marshall W.
National Heart and Lung Institute. Laboratory of Biochemical Genetics
This item is in the public domain. It may be used without permission.
From Neuroblastoma to Homeobox Genes, 1976-1992
Neuroblastoma Research, 1967-1976
Annual Report of the Laboratory of Biochemical Genetics, October 1, 1975 - September 30, 1976 (September 1976)
31 of 31
Project Number: Z01 HL 00009-02 LBG
Period Covered: July 1, 1975 through June 30, 1976
Title of Project: Cell Recognition and Synapse Formation
Names, Laboratory and Institute Affiliations, and Titles of Principal Investigators and All Other Professional Personnel Engaged
on the Project:
PI: Marshall Nirenberg, Chief, Lab. of Biochemical Genetics, LBG NHLI
Cooperating Units (if any): Behavioral Biology Branch, NICHD
Lab/Branch: Laboratory of Biochemical Genetics
Section: Section on Molecular Biology
Institute and Location: NHLI, NIH, Bethesda, MD 20014
Total Man Years: 2.2
Summary of Work: Long range objectives are to define reactions which are required for synapse formation and for transmission
of information from cell to cell.
Major Findings: Since normal neurons do not divide, clonal lines of neuroblastoma cells and somatic cell hybrids derived from
neuroblastoma cells were generated and characterized with respect to receptors, neurotransmitters, action potential ionophores,
and other properties which are required for synaptic communication. Fusion of clonal neuroblastoma cells with glioma cells
yielded clonal hybrid cell lines which synthesize, store and excrete acetylcholine; properties which are not expressed by
the parental cell lines. During the past year cells from one hybrid line were found to form synapses with cultured striated
muscle cells. Synapses between hybrid cells and muscle cells closely resemble the synapses between normal motor neurons and
striated muscle before they are fully developed. Under appropriate conditions, hybrid cells established synaptic connections
with almost every muscle cell tested; thus, synapses are synthesized in abundance. Marked differences were observed in the
efficiency of transmission across different synapses. Axonal activities which were found to be regulated include choline
acetyltransferase, acetylcholinesterase, Na+ action potential ionophore specific activities, and the rate of choline transport
Eight species of receptors have been found thus far with the hybrid cell line which forms synapses. Receptor mediated shifts
in cAMP levels, cGMP levels and membrane potentials have been identified and characterized. Thus the foundation has been
laid for studies on the effects of receptor-mediated reactions on synaptic transmission. In addition, more than 100 cell
lines which synthesize acetylcholine have been obtained and are being studied to determine that some cell lines are defective
with respect to synapse formation.
Significance to Biomedical Research: This is the first time that clonal cells of neural origin have been shown to form synapses.
Thus the set of genes which are required for synapse formation are expressed in this cell line. The model system which has
been established affords extraordinary opportunities to define synapse formation reactions and properties and correlate biochemical
events with developmental and electrophysiological phenomena.
Proposed Course: Current studies focus on determining the reactions which are required for synapse formation and factors that
regulate these reactions.
1. Greene, Lloyd A., Shain, William, Chalazonitis, Alcmene, Breakefield, Xandra, Minna, John, Coon, Hayden G. and Nirenberg,
Marshall: Neuronal properties of hybrid neuroblastoma x sympathetic ganglion cells. Proc. Natl. Acad. Sci. USA 72: 4923-4927,
2. Chalazonitis, A., Greene, L.A. and Shain W.: Excitability and chemosensitivity properties of a somatic cell hybrid between
mouse neuroblastoma and sympathetic ganglion cells. Exp. Cell Res. 96: 225-238, 1975.
3. Nelson, Phillip, Christian, Clifford and Nirenberg, Marshall: Synapse formation between clonal neuroblastoma x glioma hybrid
cells and striated muscle cells. Proc. Natl. Acad. Sci. USA 73: 123-127, 1976.
4. Nirenberg, Marshall W.: Coding of neural information by neuroblastoma cells. In: Talwar, G. P. (Ed.): Regulation of Growth
and Differentiated Function in Eukaryote Cells. New York, Raven Press, pp. 537-539, 1975
5. Thompson, Edward J., Griffith, James M., Glazer-Schoenberg, Deverera and Nirenberg, Marshall W.: An improved method for
extracellular recording of action potentials from single cultured neuroblastoma cells. Med. Biol. Eng. 13: 104-106, 1975.
6. Hamprecht, Bernd, Kemper, Wayne and Amano, Takehiko: Electrical response of glioma cells to acetylcholine. Brain Res.
101: 129-135, 1976.