RT Journal Article SR Electronic T1 Three-Dimensional Structure and Composition of CA3→CA1 Axons in Rat Hippocampal Slices: Implications for Presynaptic Connectivity and Compartmentalization JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8300 OP 8310 DO 10.1523/JNEUROSCI.18-20-08300.1998 VO 18 IS 20 A1 Shepherd, Gordon M. G. A1 Harris, Kristen M. YR 1998 UL http://www.jneurosci.org/content/18/20/8300.abstract AB Physiological studies of CA3→CA1 synaptic transmission and plasticity have revealed both pre- and postsynaptic effects. Understanding the extent to which individual presynaptic axonal boutons could provide local compartments for control of synaptic efficacy and microconnectivity requires knowledge of their three-dimensional morphology and composition. In hippocampal slices, serial electron microscopy was used to examine a nearly homogeneous population of CA3→CA1 axons in the middle of stratum radiatum of area CA1. The locations of postsynaptic densities (PSDs), vesicles, and mitochondria were determined along 75 axon segments (9.1 ± 2.0 μm in length). Synapses, defined by the colocalization of PSDs and vesicles, occurred on average at 2.7 μm intervals along the axons. Most varicosities (68%) had one PSD, 19% had 2–4 PSDs, and 13% had none. Synaptic vesicles occurred in 90% of the varicosities. One-half (53%) of the varicosities lacked mitochondria, raising questions about their regulation of ATP and Ca2+, and 8% of varicosities contained only mitochondria. Eleven axons were reconstructed fully. The varicosities were oblong and varied greatly in both length (1.1 ± 0.7 μm) and volume (0.13 ± 0.14 μm3), whereas the intervaricosity shafts were narrow, tubular, and similar in diameter (0.17 ± 0.04 μm) but variable in length (1.4 ± 1.2 μm). The narrow axonal shafts resemble dendritic spine necks and thus could promote biochemical compartmentalization of individual axonal varicosities. The findings raise the intriguing possibility of localized differences in metabolism and connectivity among different axons, varicosities, and synapses.