NMDA receptor-dependent pattern transfer from afferents to postsynaptic cells and dendritic differentiation in the barrel cortex.
N-Methyl-D-aspartate receptors (NMDARs) are important for synaptic refinement during development. In CxNR1KO mice, cortical excitatory neurons lack NR1, the essential subunit of the NMDAR, and in their primary somatosensory (S1) cortex whisker-specific cellular patterns, "barrels," are absent. Despite this cytoarchitectural defect, thalamocortical axons (TCAs) representing the mystacial vibrissae form topographically organized patterns and undergo critical period plasticity. This region-specific knockout mouse model allows for dissection of the mechanisms underlying patterning of the pre- and postsynaptic neural elements in the S1 cortex. In the absence of functional NMDARs, layer IV cell numbers are unaltered, but these cells fail to segregate into barrels. Furthermore, the dendritic fields of spiny stellate cells do not orient toward TCA terminal patches as in normal mice. Instead, they radiate in all directions covering larger territories, exhibiting profuse branching with increased spine density. Comparison of TCA patches with serotonin transporter (5-HTT) immunohistochemistry or Dil labeling also indicates that in the CxNR1KO cortex TCAs form smaller patches and individual axon terminal branching is not as well developed as in control cortex. Our results suggest that postsynaptic NMDAR activation is critical in communicating periphery-related sensory patterns from TCAs to barrel cells. When postsynaptic NMDAR function is disrupted, layer IV spiny stellate cells remain imperceptive to patterning of their presynaptic inputs and elaborate exuberant dendritic specializations.
Datwani
Akash
A
Laboratory for Behavioral Genetics, Brain Science Institute (BSI), RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
Iwasato
Takuji
T
Itohara
Shigeyoshi
S
Erzurumlu
Reha S
RS
D000344:Afferent Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D015398:Signal Transduction / Q000235:genetics; D013003:Somatosensory Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*; D013788:Thalamus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C409466:NR1 NMDA receptor; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse