Abstracts

The CA3 field in primates, unlike rats, includes proximal CA3 pyramidal cells with an apical dendrite that extends through the hilus and granule cell layer and into the molecular layer of the dentate gyrus. These unusual neurons are called [quot]dentate[quot] CA3 pyramidal cells (Buckmaster and Amaral, 2001, [italic]J Comp Neurol[/italic] 430:264). The position of their apical dendrite suggests that dentate CA3 pyramidal cells might be more responsive than other CA3 pyramidal cells to synaptic input from the entorhinal cortex to the dentate gyrus. Previous studies in rodents suggest that dentate granule cells filter or gate entorhinal input. In primates, however, dentate CA3 pyramidal cells might bypass granule cells and convey entorhinal input directly to other pyramidal cells in CA3 and CA1. To test this possibility, we stimulated the dentate gyrus molecular layer and measured the spike threshold of morphologically identified proximal CA3 pyramidal cells. Hippocampal slices were prepared from 20 adult, male, neurologically normal monkeys ([italic]Macaca fascicularis[/italic]) that were being euthanized for reasons unrelated to this experiment. Slices were recorded in an interface chamber at 31[deg]. A stimulating electrode was placed in the outer molecular layer of the dentate gyrus. Stimulus intensity was standardized by the threshold for evoking a field potential population spike (T) recorded at the border of the granule cell layer and hilus, close to the site of the recorded CA3 pyramidal cell. Proximal CA3 pyramidal cells were recorded in current-clamp mode with sharp microelectrodes. The molecular layer stimulus intensity needed to evoke an action potential was measured. Cells were labeled with biocytin and processed with DAB for visualization. CA3 pyramidal cells were classified as [quot]classical[quot] (dendrites extended into stratum radiatum and/or stratum oriens of CA3), [quot]nonapical[quot] (all dendrites confined to the pyramidal cell layer), or [quot]dentate[quot] (apical dendrite extended through the hilus and granule cell layer and into molecular layer of dentate gyrus). In response to current injection, dentate CA3 pyramidal cells responded like other CA3 pyramidal cells. In response to stimulation of the dentate gyrus molecular layer, spike thresholds were: 1.02 [plusmn] 0.13 xT (mean [plusmn] sem) for classical CA3 pyramidal cells (n=12); 0.99 [plusmn] 0.12 xT for nonapical CA3 pyramidal cells (n=23); and 0.96 [plusmn] 0.09 xT for dentate CA3 pyramidal cells (n=7). The differences were not significant (t test). These findings suggest that dentate CA3 pyramidal cells have similar spike thresholds to stimulation of the dentate gyrus molecular layer as other types of CA3 pyramidal cells. We cannot exclude the possibility that differences might be detected with more physiological stimulation methods. The role of dentate CA3 pyramidal cells is unclear, but based on these findings, they do not appear to circumvent the dentate gate. (Supported by NIH/NINDS (NS40276))