Complementary techniques for unbiased stereology of brain ultrastructure

Estimating synaptic density is central to any examination of synaptic change. Barring techniques involving exhaustive sectioning, the traditional method for this estimation is the double dissector technique, which derives a ratio of synapses per neuron. This ratio, however, may not always equate to an absolute number of synapses. In contrast, the unbiased brick, while free of these problems, is limited by changes in reference space and cannot provide information on synaptic connectivity. Thus, the ideal analysis is to derive both synaptic measures. When these measures agree, one can discount changes in extraneous factors influencing synaptic counts.