Back to Search
Start Over
A role for atypical cadherin Celsr3 in hippocampal maturation and connectivity.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Oct 03; Vol. 32 (40), pp. 13729-43. - Publication Year :
- 2012
-
Abstract
- Atypical cadherin Celsr3, a regulator of planar cell polarity, is critical for the development of the axonal blueprint. We previously showed that expression of Celsr3 is necessary to establish forebrain connections such as the anterior commissure and thalamocortical and corticospinal tracts. The requirement for Celsr3 during hippocampal wiring and its action in the hippocampus remain largely unexplored. Here, we compared the connectivity and maturation of the hippocampal formation in Celsr3|Foxg1 and Celsr3|Dlx mice. Celsr3 is inactivated in the whole telencephalon, including the hippocampal primordium, in Celsr3|Foxg1 mice, and in the early basal telencephalon, including ganglionic eminences and ventral diencephalon, in Celsr3|Dlx mice. Behavioral tests showed that both mutants were hyperactive and had impaired learning and memory. Abnormal cytoarchitecture of CA1, CA3, and dentate gyrus was found in the Celsr3|Foxg1 mutant, in which afferent and efferent hippocampal pathways, as well as intrinsic connections, were dramatically disrupted. In Celsr3|Dlx mutant mice, hippocampal cytoarchitecture was mildly affected and extrinsic and intrinsic connectivity moderately disturbed. In both mutants, pyramidal neurons in CA1 harbored atrophic dendritic trees, with decreased synapse density and increased proportion of symmetric versus asymmetric synapses, and long-term potentiation was altered. In contrast, mutant hippocampal neurons extended neurites that were normal, even longer than those of control neurons, indicating that anomalies in vivo are secondary to defective connections. Postnatal neurogenesis was preserved and mutant interneurons were able to migrate to the hippocampus. Thus, like in neocortex, Celsr3 is required for hippocampal development, connectivity and function, and for pyramidal cell maturation.
- Subjects :
- Animals
Cadherins deficiency
Cadherins genetics
Cell Movement
Cells, Cultured metabolism
Cells, Cultured ultrastructure
Dendrites ultrastructure
Female
Fluorescent Dyes
Forkhead Transcription Factors deficiency
Forkhead Transcription Factors genetics
Forkhead Transcription Factors physiology
Hippocampus growth & development
Hippocampus physiology
Hippocampus ultrastructure
Homeodomain Proteins genetics
Homeodomain Proteins physiology
Hyperkinesis embryology
Hyperkinesis pathology
Interneurons physiology
Learning Disabilities pathology
Male
Maze Learning
Memory Disorders pathology
Mice
Mice, Knockout
Nerve Tissue Proteins deficiency
Nerve Tissue Proteins genetics
Nerve Tissue Proteins physiology
Neurogenesis
Pyramidal Cells ultrastructure
Reaction Time
Receptors, Cell Surface deficiency
Receptors, Cell Surface genetics
Synapses ultrastructure
Transcription Factors deficiency
Transcription Factors genetics
Transcription Factors physiology
Cadherins physiology
Hippocampus embryology
Hyperkinesis genetics
Learning Disabilities genetics
Memory Disorders genetics
Neural Pathways ultrastructure
Pyramidal Cells physiology
Receptors, Cell Surface physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 32
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 23035085
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1965-12.2012