Witcher et al recently published a paper looking at the relationship between astroglia and synapse morphology of three epileptic patients and one control patient. Following surgical resection, these patients allowed for the analysis of some of their hippocampal brain tissue. It took the surgeons less than 2 minutes to resect the hippocampus after cutting the main blood supply, and around 5 mins to collect the samples into the cold and oxygenated artifical cerebrospinal fluid. The quick pace produces healthy, physiologically relevant tissue samples. Eventually these hippocampal samples were cut into 40-50 sections ~45 nm thick and visualized with transmission electron microscopy. These are some of the components that they detected:
- Dendritic spines. These were classified on the basis of their morphology into thin, mushroom, stubby, and giant. Also, the researchers were able to determine the amount of extracellular space around them, the appearance of their organelles, and the organization of their microtubules.
- Docked presynaptic vescicles. These are vescicles that have been primed to form “soluble N-ethylmaleimide-sensitive factor attached protein receptor” complexes, and thus are generally immobilized at the release site before exocytosis. Vescicles were counted as docked if the vescicular membrane was adjacent to the plasma membrane of the presynaptic axon at the “active zones” of the synapse that have high postsynaptic density.
- Neurotransmitter type of synapse. On the basis of morphology, the researchers could make educated guesses as to the neurotransmitter type of the synapse. For example, some asymmetric synapses with round vesicles were assumed to be excitatory and gluatamergic. Some symmetric synapses were assumed to be inhibitory and GABAergic.
One of their findings was that the number of docked synaptic vesicles correlated positively with the postsynaptic density of the synapse, r = 0.68 in the tissue with mild neurodegeneration. This suggests a coordination between pre- and post-synaptic composition that has been found in rats and assumed to be the case in humans. They also found more invasive astroglia processes as the severity of the neurodegeneration increased, indicating that reactive astrogliosis may be responsible for some of the epileptic symptoms of the patients.
Witcher MR, et al. 2009 Three-dimensional relationships between perisynaptic astroglia and human hippocampal synapses. Glia doi:10.1002/glia.20946 .
Nofal S, et al. 2007 Primed Vesicles Can Be Distinguished from Docked Vesicles by Analyzing Their Mobility. J Neuro doi:10.1523/JNEUROSCI.4714-06.2007.