THE ABSENCE OF A MAJOR CA2+ SIGNALING PATHWAY IN GABAERGIC NEURONS OFTHE HIPPOCAMPUS

The Ca2+/calmodulin-dependent protein phosphatase 2B or calcineurin (C N) participates in several Ca2+-dependent signal transduction cascades and, thus, contributes to the short and long term regulation of neuro nal excitability. By using a specific antibody to CN, we demonstrate i ts absence from hippocampal interneurons and illustrate a physiologica l consequence of such CN deficiency. Consistent with the lack of CN in interneurons as detected by immunocytochemistry, the CN inhibitors FK -506 or okadaic acid significantly prolonged N-methyl-D-aspartate chan nel openings recorded in the cell-attached mode in hippocampal princip al cells but not those recorded in interneurons. Interneurons were als o devoid of Ca2+/calmodulin-dependent protein kinase II alpha, yet man y of their nuclei contained the cyclic AMP-responsive element binding protein. On the basis of the CN and Ca2+/calmodulin-dependent protein kinase II alpha deficiency of interneurons, entirely different biochem ical mechanisms are expected to govern Ca2+-dependent neuronal plastic ity in interneurons versus principal cells.