Stereological estimation of the total number of neurons in the murine hippocampus using the optical disector

Using a stereological method, the optical disector, we examined three inbre d strains of mice (NZB/BINJ, DBA/2, and C57BL/6J) for morphological differe nces in volume, neuronal number, and density of the pyramidal cell and dent ate gyrus granule cell layers of the hippocampus. We found significant diff erences in volume and neuronal number for both regions between the three st rains at 9 weeks of age, hut only modest differences in neuronal density. T he left dentate volume was 90% larger in the NZB strain and 70% greater in the DBA strain (P < 0.0001), and the left pyramidal cell layer was 144% lar ger in the NZB strain and 150% larger in the DBA strain, than in the B6 str ain (P < 0.0001). Neuron number in the left dentate was 81% greater in NZB and 37% greater in DBA (P < 0.001), and in the left pyramidal cell layer 11 8% greater in the NZB and 92% greater in the DBA (P < 0.01). Differences in neuronal density of the left dentate were not significant (P = 0.060, ns). For the left pyramidal cell layer, neuronal density was 14% greater in B6 and 34% greater in NZB than the DBA strain (P = 0.016). No significant diff erences were found in left-right laterality, or according to sex. We found that strain accounted for 60% of the variance in hippocampal volume and 44% of neuron number. These differences thus mainly reflect genetic variation in hippocampal volume and may have important implications for brain evoluti on, behaviour, and human diseases where hippocampal degeneration is involve d. (C) 1999 Wiley-Liss,Inc.