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mRNA distribution within dendrites: relationship to afferent innervation
1Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Abstract:
The majority of neuronal mRNAs are confined to cell bodies, but a few mRNAs are present at high levels in dendrites. Here we report an initial analysis of the relationship between afferent innervation and the distribution of mRNA within dendritic fields. In situ hybridization techniques were used to compare the subcellular distribution of dendritic mRNAs in principal neurons of the hippocampal formation in vivo. The mRNA encoding the alpha subunit of calcium/calmodulin dependent protein kinase II (CAMII kinase) was present at high levels throughout the layers that contain the dendrites of hippocampal pyramidal cells and dentate granule cells. In contrast, the mRNA encoding the high molecular weight microtubule-associated protein MAP2 had a more limited distribution. In the dentate gyrus, labeling for MAP2 was present in a discrete band in the lamina containing proximal dendrites and decreased to low levels in laminae containing distal dendrites. This laminar pattern resembles the distinct terminations of the commissural/associational projection (high MAP2 labeling) and the entorhinal projection (lower MAP2 labeling) upon dendrites of granule cells. To determine if the differential distribution of dendritic mRNAs was regulated by either the presence or activity of afferents, we evaluated mRNA distribution in the dentate molecular layer following (1) removal of the entorhinal input by lesions of the entorhinal cortex or (2) prolonged delivery of potentiating stimulation to entorhinal afferents. Denervation led to modest decreases in the levels of mRNAs for both CAMII and MAP2 but did not lead to detectable alterations in mRNA distribution. Also, prolonged stimulation did not lead to detectable alterations in MAP2 or CAMII mRNA distribution although such stimulation clearly elevated the expression of mRNA for glial fibrillary acidic protein (GFAP).
Insights
Neuronal mRNA distribution in dendrites is not significantly altered by afferent input removal or stimulation. This suggests local dendritic factors, not just innervation, regulate mRNA localization in hippocampal neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neuronal mRNAs are primarily in cell bodies, but some are found in dendrites.
- Understanding dendritic mRNA distribution is key to neuronal function and plasticity.
Purpose of the Study:
- To investigate the relationship between afferent innervation and dendritic mRNA distribution in hippocampal neurons.
- To determine if mRNA distribution is regulated by the presence or activity of afferent inputs.
Main Methods:
- In situ hybridization was used to analyze mRNA distribution in hippocampal principal neurons.
- Entorhinal cortex lesions and prolonged afferent stimulation were employed to manipulate innervation.
Main Results:
- Calcium/calmodulin dependent protein kinase II (CAMII) kinase mRNA was widespread in dendrites.
- Microtubule-associated protein 2 (MAP2) mRNA showed a more limited, laminar distribution in the dentate gyrus.
- Denervation caused minor decreases in CAMII and MAP2 mRNA levels but no distribution changes.
- Prolonged stimulation did not alter MAP2 or CAMII mRNA distribution but increased glial fibrillary acidic protein (GFAP) mRNA.
Conclusions:
- Afferent innervation does not appear to significantly regulate the laminar distribution of CAMII and MAP2 mRNAs in hippocampal dendrites.
- Local factors within dendrites may play a more critical role in mRNA localization than previously thought.