Dept Home Page > Department Faculty > Ruth Heidelberger, M.D., Ph.D.

Ruth Heidelberger, M.D., Ph.D.

Associate Professor

Telephone: 713.500.5624
E-mail: ruth.heidelberger@uth.tmc.edu

Mechanisms Of Neurotransmitter Release

A: Illustrates the capacitance record from an isolated synaptic terminal in a flash-photolysis experiment. At the arrow, a flash of UV light was given to photolytically release calcium from its caging group and elevate internal calcium. The lower panel shows the internal calcium concentration as measured with a flourescent calcium indicator dye. B: The calcium dependence of the rate of synaptic vesicle fusion can be determined from experiments similar to that shown in A. For each terminal, the capacitance rise was fitted with a single exponential and the rate constant of this fit was plotted against the post-flash calcium concentration. (see Heidelberger et al., 1994)

The primary function of a presynaptic nerve terminal is to release neurotransmitter into the synaptic cleft in an appropriate manner. The amount and pattern of transmitter release will depend upon several factors, including how long and to what level the presynaptic calcium concentration is elevated and the number of synaptic vesicles that are available for fusion. Knowledge of how these factors are regulated is of fundamental importance and will aid us in understanding the contribution of the presynaptic terminal to changes in synaptic efficacy and memory.

In my laboratory, we examine these questions at the single cell level. Standard electrophysiologic patch-clamp techniques are combined with more specialized methods that include the use of fluorescent indicator dyes (to measure the intracellular calcium concentration) and flash-photolysis of "caged" compounds (to rapidly and uniformly change the intracellular concentration of a compound), and membrane capacitance measurements (to electrically detect fusion of synaptic vesicles with the presynaptic membrane). These techniques allow us to study exocytosis in a living neuron in real-time. Currently, we are using these methods to examine the role of ATP in the regulation of neurotrans-mitter release. Other projects include studying the effects of second messengers and protein phosphorylation on neurotransmitter release, identifying the synaptic proteins that mediate these changes, and developing a more detailed description of calcium entry and calcium handling within a nerve terminal.

Although general principles can be obtained from the study of exocytosis in non-neuronal secretory cells, it is only in the nervous system that speed and fidelity are critical design considerations. Therefore, most of our studies are performed on nerve terminals isolated from vertebrate retina. These synaptic terminals have the advantage that they are unusually large and accessible relative to other CNS nerve terminals. It is anticipated that knowledge about the regulation of neurotransmitter release obtained from these retinal nerve terminals will not only tell us about how some nerve terminals in the CNS behave, but will also yield insights into how the retina encodes and relays visual information.

Selected Reading

Heidelberger R. (2001) Electrophysiological approaches to the study of neuronal exocytosis and synaptic vesicle dynamics.  Rev Physiol Biochem Pharmacol. 2001;143:1-80.

Heidelberger R. (2001) ATP is required at an early step in compensatory endocytosis in synaptic terminals. J Neurosci. 21(17):6467-74.

Heidelberger R, Sterling P, Matthews G. (2002) Roles of ATP in depletion and replenishment of the releasable pool of synaptic vesicles.  J Neurophysiol. 88(1):98-106. 

Heidelberger R, Zhou ZY, Matthews G. (2002) Multiple components of membrane retrieval in synaptic terminals revealed by changes in hydrostatic pressure.  J Neurophysiol. 88(5):2509-17.

Heidelberger R, Wang MM, Sherry DM. (2003) Differential distribution of synaptotagmin immunoreactivity among synapses in the goldfish, salamander, and mouse retina.  Vis Neurosci. 20(1):37-49.

Thoreson WB, Rabl K, Townes-Anderson E, Heidelberger R. (2004) A highly Ca2+-sensitive pool of vesicles contributes to linearity at the rod photoreceptor ribbon synapse.  Neuron 42(4):595-605.

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