Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles

Abstract

Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.

Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

“…Dense-core vesicles package neuropeptides and small-molecule neurotransmitters such as monoamines, which are capable of exciting action potentials in neurons (Araneda and Firestein, 2006; Ramirez-Franco et al, 2016; Zhou et al, 2016). Monoamines include tryptophan-derived serotonin (5HT) and tyrosine-derived catecholamines, such as dopamine, epinephrine and norepinephrine.…”

Dense‐core vesicle biogenesis and exocytosis in neurons lacking chromogranins A and B

“…A recent study showed that some Cgs are selectively excluded from certain populations of neurons: CgB is absent in hippocampal interneurons (Ramírez‐Franco et al . ). Secretogranins II–IV are the most likely candidates, to provide redundant functionality.…”

Characterization of Tissue Plasminogen Activator Expression and Trafficking in the Adult Murine Brain

“…For, tPA appears to be largely localized to the soma of inhibitory interneurons ( Fredriksson et al, 2015 ) and to the axons of excitatory neurons (Louessard et al, 2015). While knowledge about dense core vesicle trafficking is still nascent compared to synaptic vesicle trafficking, there is evidence which demonstrates regionally-specific, differential trafficking of the neuropeptide NPY to dendrites and axons ( Ramamoorthy et al, 2011 ) and that excitatory and inhibitory neurons in the hippocampus exhibit different dense core vesicle molecular machinery ( Ramírez-Franco et al, 2016 ).…”