Hippocampal tyrosine kinase A receptors are restricted primarily to presynaptic vesicle clusters

Adult septohippocampal cholinergic neurons are dependent on trophic support for normal functioning and survival; these effects are largely mediated by the tyrosine kinase A receptor (TrkA), which binds its ligand, nerve growth factor (NGF), with high affinity. To determine the subcellular localization of TrkA within septohippocampal terminal fields, two rabbit polyclonal antisera to the extracellular domain of TrkA were localized immunocytochemically in rat dentate gyrus by light and electron microscopy. By light microscopy, TrkA immunoreactivity was found mostly in fine, varicose fibers primarily in the hilus and, to a lesser extent, in the granule cell and molecular layers. By electron microscopy, the central and infragranular regions of the hilus contained the highest densities of TrkA-immunoreactive profiles. Most TrkA-labeled profiles were axons (31% of 3,473), axon terminals (20%), and glia (38%); fewer were dendrites (6%), dendritic spines (5%), and granule cell and interneuron somata (<1%). TrkA immunolabeling in axons and axon terminals was discrete, often concentrated in patches of small synaptic vesicles that were adjacent to somatic and dendritic profiles. TrkA-labeled terminals formed both asymmetric and symmetric synapses, primarily with dendritic shafts and spines. TrkA-immunoreactive glial profiles frequently apposed terminals contacting dendritic spines. The findings that presynaptic profiles contain TrkA immunolabeling in sites of vesicle accumulation suggest that NGF binding to TrkA may influence transmitter release. The presence of TrkA immunoreactivity in somata, dendrites, and glia further suggests that cells within the dentate gyrus may take up NGF.