Characteristics of Receptors for Excitatory Neurotransmitters

The purpose of this research is to investigate the properties of receptors for excitatory neurotransmitters in the central nervous system CNS, particularly those for acidic amino acids and related derivatives. Most of the synapses in the CNS appear to use these molecules as neurotransmitters but little is known about their receptor properties. Various phosphonic acid derivatives and toxins appear to act directly or indirectly on these receptors. This research uses a newly developed anatomical method to localize the various receptor subtypes in the rodent brain. Electrophysiological analysis is used to record the physiological response to various agonists and antagonists that act on these receptors. Our results have shown, for the first time, that glutamate receptors are most concentrated in the cerebral cortex and hippocampus in addition to key pathways from the peripheral to the CNS. Electrophysiological analysis indicates that select antagonists e.g., 2-amino-4-phosphonobutyric acid will block synaptic transmission at some pathways, while other antagonists in this series e.g., 2-amino-5-phosphonopentanoic acid will block a type of synaptic short-term memory at other pathways without interfering with normal synaptic transmission. These compounds are thus highly selective in their mode of action.