Abstract

The purpose of this article is to review the contributions of transmission electron microscopy studies to the understanding of brain circuits and neurotransmitter systems. Our views on the microstructure of connections between neurons have gradually changed, and now we recognize that the classical mental image we had on a chemical synapse is no longer applicable to every neuronal connection. We highlight studies that converge to point out that, while the most prevalent fast transmitters in the brain, glutamate and GABA, are stored in small, clear synaptic vesicles (SSV) and released at synapses, neuropeptides are exclusively stored in large dense core vesicles (LDCV) and released extrasynaptically. Amine transmitters are preferentially, but not exclusively, accumulated in LDCV and may be released at synaptic or extrasynaptic sites. We discuss evidence suggesting that axon terminals from pyramidal cortical neurons and dorsal thalamic neurons lack LDCV and therefore could not use neuropeptides as transmitters. This idea fits with the fast, high temporal resolution information processing that characterizes cortical and thalamic function.