The secret life of memory receptors

The canonical hippocampal NMDA memory receptor also controls the release of the transmitter glutamate and the growth factor BDNF.

Trafficking of Amino Acids between Neurons and Glia In Vivo. Effects of Inhibition of Glial Metabolism by Fluoroacetate

Glial-neuronal interchange of amino acids was studied by 13C nuclear magnetic resonance spectroscopy of brain extracts from fluoroacetate-treated mice that received [1,2-13C]acetate and [1-13C]glucose simultaneously. [13C]Acetate was found to be a specific marker for glial metabolism even with the large doses necessary for nuclear magnetic resonance spectroscopy. Fluoroacetate, 100 mg/kg, blocked the glial, but not the neuronal tricarboxylic acid cycles as seen from the 13C labeling of glutamine, glutamate, and γ-aminobutyric acid. Glutamine, but not citrate, was the only glial metabolite that could account for the transfer of 13C from glia to neurons. Massive glial uptake of transmitter glutamate was indicated by the labeling of glutamine from [1-13C]glucose in fluoroacetate-treated mice. The C-3/C-4 enrichment ratio, which indicates the degree of cycling of label, was higher in glutamine than in glutamate in the presence of fluoroacetate, suggesting that transmitter glutamate (which was converted to glutamine after release) is associated with a tricarboxylic acid cycle that turns more rapidly than the overall cerebral tricarboxylic acid cycle.

Reversal of GABA Actions by Neuronal Trauma

GABA is the most prevalent inhibitory transmitter in the adult brain where it reduces neuronal activity mainly by opening chloride channels and hyperpolarizing the membrane potential. Surprisingly, after some types of neuronal trauma, GABA exerts a different action, depolarizing the membrane potential, raising cytoplasmic calcium levels, and increasing neuronal activity. After trauma, GABA can generate cytoplasmic calcium rises even larger than those elicited by the excitatory transmitter glutamate. Large GABA-mediated increases in intracellular calcium could be toxic. Furthermore, if inhibitory neuronal circuits switched to excitatory actions, maladaptive signaling may be generated in affected pathways. These depolarizing actions of GABA after injury are similar to GABA's function in early neuronal development. Neuronal injury, thus, may generate a recapitulation of GABA's role in ontogeny. NEUROSCIENTIST 3:281–286, 1997