Differential dendritic targeting of AMPA receptor subunit mRNAs in adult rat hippocampal principal neurons and interneurons

Abstract

In hippocampal neurons, AMPA receptors (AMPARs) mediate fast excitatory postsynaptic responses at glutamatergic synapses, and are involved in various forms of synaptic plasticity. Dendritic local protein synthesis of selected AMPAR subunit mRNAs is considered an additional mechanism to independently and rapidly control the strength of individual synapses. We have used fluorescent in situ hybridization and immunocytochemistry to analyze the localization of AMPAR subunit (GluA1-4) mRNAs and their relationship with the translation machinery in principal cells and interneurons of the adult rat hippocampus. The mRNAs encoding all four AMPAR subunits were detected in the somata and dendrites of CA3 and CA1 pyramidal cells and those of six classes of CA1 γ-aminobutyric acid (GABA)ergic interneurons. GluA1-4 subunit mRNAs were highly localized to the apical dendrites of pyramidal cells, whereas in interneurons they were present in multiple dendrites. In contrast, in the dentate gyrus, GluA1-4 subunit mRNAs were virtually restricted to the somata and were absent from the dendrites of granule cells. These different regional and cell type-specific labeling patterns also correlated with the localization of markers for components of the protein synthesis machinery. Our results support the local translation of GluA1-4 mRNAs in dendrites of hippocampal pyramidal cells and CA1 interneurons but not in granule cells of the dentate gyrus. Furthermore, the regional and cell type-specific differences we observed suggest that each cell type uses distinct ways of regulating the local translation of AMPAR subunits.

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

“…nNOS produces the gas-neurotransmitter NO, which is involved in a number of physiological and pathological processes, including vasodilatation and RNS-mediated damage. iii) Goat anti-somastostatin (SOMA) [code# sc-7819, 1:1,000 dilution and characterized previously (26,27); Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA]. SOMA is a neuroendocrine peptide hormone and regulates a number of secondary hormones via its G protein-coupled receptors.…”

Immunoreactivity of the calbindin D28k in the parahippocampal gyrus of chinchilla

“…The third subclass consists of regularly communicating interneurons that demonstrate the presence of other calcium-binding proteins (29). neuromodulators to synaptic cleft is associated with the synaptic plasticity, which also depends on the appropriate concentration of calcium ions in the cell (8,10). Varied distribution of this protein in different classes of PG neurons requires further studies.…”

“…The presence of glutamic acid as an excitatory neurotransmiter in the primary cells is particulary important for memorising process and learning. Gamma-aminobutyric acid (GABA), present in interneurons, is responsible for the inhibitory effect on other interneurons as well as on primary cells, which form a network involved in the control of neuronal activity (8,9,14,27). As it was shown in guinea pig, a specific topographical localisation of PG participates in bidirectional communication between the hippocampus and neocortex (23).…”

Single-molecule insights into mRNA dynamics in neurons

“…Indeed, early demonstration of in situ hybridization in hippocampal slices distinguished mRNAs that were present in dendrites from those which were selectively excluded [18–20]. Moreover, contrasting patterns of mRNA localization in different hippocampal subfields strongly suggested that not only are neurons capable of sorting mRNAs, but that localization of a single species of mRNA could vary between neuronal subtypes and brain regions [18,21–24]. How the differential subcellular localization of a single mRNA species is accomplished remains unknown.…”

“…Due to the central role glutamate receptors play in synaptic transmission, it is likely that neurons have developed multiple and redundant ways to modulate expression during periods of plasticity. Moreover, differential neuronal signaling properties could lead to different AMPA receptor mRNA expression and localization profiles in various neuronal subtypes and brain regions [24]. While improvements in detection of RNA in neurons will inevitably introduce some discrepancies w ith previously published reports, the findings will eventually enhance our understanding of local protein synthesis in neurons.…”