A fundamental property of neuronal networks in Ammon's horn is that each area comprises
a single glutamatergic cell population and various types of GABAergic neurons. Here
we describe an exception to this rule, in the form of granule cells that reside within
the CA3 area and function as glutamatergic nonprincipal cells with distinct properties.
CA3 granule cells in normal, healthy rats, similarly to dentate gyrus granule cells,
coexpressed calbindin and the homeobox protein Prox1. However, CA3 granule cells were
located outside of the dentate gyrus, often hundreds of micrometers from the hilar
border, in the lucidum and radiatum layers. CA3 granule cells were present in numbers
that were comparable to the rarer GABAergic neuronal subtypes, and their somato-dendritic
morphology, intrinsic properties, and perforant path inputs were similar to those
of dentate gyrus granule cells. CA3 granule cell axons displayed giant mossy fiber
terminals with filopodial extensions, demonstrating that not all mossy fibers originate
from the dentate gyrus. Somatic paired recordings revealed that CA3 granule cells
innervated CA3 pyramidal and GABAergic cells similarly to conventional mossy fiber
synapses. However, CA3 granule cells were distinct in the specific organization of
their GABAergic inputs. They received GABAergic synapses from cholecystokinin-expressing
mossy fiber-associated cells that did not innervate the dentate granule cell layer,
and these synapses demonstrated unusually strong activity-dependent endocannabinoid-mediated
inhibition of GABA release. These results indicate that granule cells in the CA3 constitute
a glutamatergic, nonprincipal neuronal subtype that is integrated into the CA3 synaptic
network.
