Long-term information storage in the adult brain is increasingly believed to involve the cellular mechanism of synaptic development, requiring active protein synthesis by participating neurons for long-term memory an long-lasting modifications of synaptic strength. Local protein translation in dendrites has been proposed to explain the use of newly synthesized proteins at selective synapses during synaptogenesis, and in cases of synapse-specific plasticity. Synaptic plasticity in vitro requires postsynaptic fusion of vesicles delivering integral membrane and/or secretory proteins. The subcellular organization of the protein synthetic compartments near synapses, for synthesis of secretory and integral membrane proteins, has not been determined. This proposal tests the general hypothesis that local protein synthesis of (secretory and/or integral membrane) proteins contributes to dendritic spine development, regulation, and synaptogenesis.
AIM I will determine if portions of the endomembrane in distal dendrites display immunolabeling for post-RER protein synthetic compartments. Antigens highly concentrated in early, middle, or late protein synthetic compartments will be ultrastructurally localized within distal portions of the hippocampal CAl stratum radiatum when synapse and spine densities reach adult values.
In AIM II dendritic protein synthetic compartments will be analyzed with respect to stages of synaptogenesis and dendritic spine formation to determine if the dendritic protein synthetic pathway is established before, during, or following synaptogenesis and dendritic spine development. This proposal will contribute toward understanding the subcellular distribution and development of protein synthetic compartments in distal dendritic spines and dendrites, which is crucial to understanding the contribution of local protein synthesis to synaptic and dendritic spine function, development, and modulation. Determining the capability of the neuronal endomembrane system for protein synthesis within dendrites and dendritic spines is vital to understanding synapse-specific and dendritic spine-specific modifications, particularly because of the importance of dendritic spines to neurological disorders, synaptic stability and plasticity. The R21 grant mechanism provides for this investigation by supporting initial research and development of a body of date upon which significant future research may be built.
| McCarthy, J Brian; Milner, Teresa A (2003) Dendritic ribosomes suggest local protein synthesis during estrous synaptogenesis. Neuroreport 14:1357-60 |
| McCarthy, J B; Barker-Gibb, A L; Alves, S E et al. (2002) TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous. Glia 38:36-44 |
