Density of neurons and synapses in the cerebral cortex of the mouse

Abstract

Quantitative anatomical investigations provide the basis for functional models. In this study the density of neurons and synapses was measured in three different areas (8, 6, and 17) of the neocortex of the mouse. Both kinds of measurements were made on the same material, embedded in Epon/Araldit. In order to determine the synaptic density per mm3, the proportion of synaptic neuropil was also measured; it was found to be 84%. The cortical volume occupied by cell bodies of neurons and glia cells amounted to 12%, that by blood vessels to 4%. The total average was 9.2 x 10(4) neurons/mm3 and 7.2 x 10(8) synapses/mm3. About 11% of the synapses were of type II. The density of neurons increased with decreasing cortical thickness; thus the number of neurons under a given surface area was about constant. The synaptic density, on the other hand, was almost constant in the three areas, the number of synapses under a given cortical surface area tended, therefore, to increase with cortical thickness. The average number of synapses per neuron was 8,200, with a tendency to increase with increasing cortical thickness. Shrinkage of the tissue was also measured for various staining techniques. No shrinkage occurred during perfusion with 3.7% formaldehyde or with a solution of buffered paraformaldehyde and glutaraldehyde and during fixation in situ. Electron microscopical material showed almost no shrinkage, whereas Nissl-preparations on paraffin-embedded material had only 43% of their original volume. After Nissl stain on frozen sections the volume had shrunken to 68% and after Golgi impregnation and embedding in celloidin to 70%. The total volume of the neocortex was 112 mm3 (both hemispheres together). The total number of neurons was thus 1.0 x 10(7) and the total number of synapses 8.1 x 10(10).

The basic nonuniformity of the cerebral cortex

“…According to the original study (10), the number of neurons beneath 1 mm 2 of cortical surface is Ϸ147,000 in the mouse, rat, cat, macaque monkey, and man, or 97,351 when corrected for shrinkage. Although one study (11) found that the number of neurons under a given cortical surface in mice is constant and close to the number estimated by Rockel et al (10), and the density of neurons increases with decreasing cortical thickness, studies on other mammalian orders have found numbers that contradict the predicted numerical uniformity of the cerebral cortex. Across insectivores, for instance, the number of neurons beneath 1 mm 2 was found to decrease from close to 70,000 to Ͻ40,000 together with increasing brain size and decreasing neuronal density (13).…”

“…In that study, the authors used twodimensional counts of neurons in sections of the cerebral cortex from mouse, rat, cat, macaque, and man, and concluded that a uniform number of neurons beneath 1 mm 2 is present across species. The notion of numerical uniformity, although supported by data obtained through light microscopy analysis in the mouse (11), has since been disputed by separate research studies within (12,13) and across mammalian orders (14). Despite the evidence to the contrary, most models of cortical evolution and connectivity still assume that cortical columns hold a constant number of neurons across species (7,8,15,16).…”

Indirect measurement of regional axon diameter in excised mouse spinal cord with q-space imaging: Simulation and experimental studies

“…Contradictory reports suggest that histology has no affect (Schuz and Palm, 1989) and linearly decreases axon diameters (O'Kusky and Colonnier, 1982). However, tissue shrinkage is not expected for freshly excised or perfusion fixed tissues (Schuz and Palm, 1989). Comparison with QSI would therefore mitigate problems with tissue shrinkage and sample registration.…”

The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost

“…The appealing alternative view that total connectivity, gauged from the total number of synapses in the brain, should be a direct determinant of brain processing capabilities runs into the same difficulty. Although this possibility remains to be examined systematically, the few pieces of evidence available in the literature suggest that synaptic density is constant across species (14)(15)(16)(17). If that is indeed the case, the total numbers of brain synapses would be simply proportional to brain size and the differences in cognitive abilities between brains of a similar size would, again, be left unaccounted for.…”