Neurotransmitter release was thought to be integral to neuronal identity. Borodinsky et al. show that activity can control not just the levels of the neurotransmitter produced, but whether the neuron produces an inhibitory or excitatory neurotransmitter. The changes in neurotransmitter content appeared to occur independently from the other markers of neuronal identity. Using Xenopus laevis embryos, the authors either inhibited neural activity by hyperpolarization through overexpression of K+ channels or stimulated neural activity by overexpression of Na+ channels. Alternatively, the authors pharmacologically manipulated calcium spike activity by implanting drug-containing agarose beads. Conditions resulting in increased activity resulted in an increase in the number of inhibitory neurons [γ-aminobutyric acid (GABA)- or glycine-positive neurons] and a reduction in excitatory neurotransmitter content (acetylcholine or glutamate-positive neurons) without any change in the number of neurons expressing various identifying marker proteins. The converse was true for conditions that resulted in decreased activity: an increase in excitatory neurons and a decrease in inhibitory neurons. In some cases, both excitatory and inhibitory transmitters were present in the same neuron. Neurotransmitter content was also altered in low-density, cultured neurons that lacked synaptic contacts by manipulating calcium spike frequencies. In vitro, there was a window in which changes in activity could alter the neurotransmitter phenotype of the neurons; thus, there may be a point at which neurotransmitter content is set and cannot be overridden by changes in activity. See Goulding for a discussion of these results.
L. N. Borodinsky, C. M. Root, J. A. Cronin, S. B. Sann, X. Gu, N. C. Spitzer, Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429, 523-530 (2004). [Online Journal]
M. Goulding, A matter of balance. Nature 429, 515-516 (2004). [Online Journal]