This study examined glutamate-activated current responses of mouse and huma
n Cajal-Retzius (C-R) cells. Thin cortical slices were prepared from the br
ains of mice 4-6 days after birth and from those of midgestational human fe
tuses. Both human and mouse C-R cells displayed glutamate-induced whole-cel
l current responses that were voltage-dependent and included an N-methyl-D-
aspartate (NMDA) receptor-mediated component that was differentially sensit
ive to blockade by the NMDA receptor antagonists 2-amino-5-phosphonovaleric
acid and ifenprodil. alpha -Amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA), a non-NMDA glutamate receptor agonist, induced current respons
es in human but not in mouse C-R cells. These results, taken together, lead
us to conclude that human C-R cells express both NMDA and AMPA types of gl
utamate receptors very early during development of the cortex. In contrast,
mouse C-R cells express only the NMDA type of glutamate receptor. Thus we
demonstrate a species-dependent sensitivity of C-R cells to glutamate and p
ostulate that this differential sensitivity may account in part for a speci
es-dependent difference in the persistence of C-R cells during cortical dev
elopment.