Pathway-specificity in N-methyl-D-aspartate receptor-mediated synaptic inputs onto subplate neurons.
The subplate plays an important role in forming neuronal connections during early cortical development. We characterized by the use of whole-cell and cell-attached patch-clamp recordings in coronal brain slices from newborn mice (postnatal day [P] 0-3) the functional properties of two major pathways onto subplate neurons (SPn), the thalamocortical and the intra-subplate synaptic input. The two afferent pathways were stimulated extracellularly with bipolar electrodes placed in the thalamus and the subplate, respectively. Synaptically evoked and pharmacologically isolated N-methyl-d-aspartate receptor (NMDAR) -mediated responses with an onset latency of approximately 6 ms could be reliably recorded in P0-3 SPn. Whereas the intra-subplate input revealed a pronounced facilitation using paired pulse stimulation at 60-120 ms or repetitive activation at 10-40 Hz, the thalamocortical input was either stable or markedly suppressed under these conditions. Single cell reverse transcription PCR revealed the expression of the NR2A, B and D subunit in all investigated SPn. The intra-subplate and the thalamocortical synaptic input did not differ in their sensitivity to NVP-AAM077 or ifenprodil, indicating that both synaptic inputs have a similar NR2A/2B subunit composition. At P0, NMDAR-mediated synaptic inputs arising from the thalamus were significantly larger as compared with the intra-subplate input. This difference could no longer be detected in P2-3 SPn, indicating an input-specific developmental regulation during the first Ps. Our data indicate that the thalamocortical and intra-subplate synaptic input onto P0-3 SPn differs in functional, molecular and developmental properties. The intra-subplate synaptic input shows more mature functional properties and sustains high stimulation frequencies, thereby promoting the immature thalamocortical input to the developing neocortical circuit.
Hirsch
S
S
Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, Mainz, Germany.
Luhmann
H J
HJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D051379:Mice; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid