CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity.
We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing
a previously undetected membrane potential-dependent firing or regular firing phenotype,
due to different low-voltage-activated potassium currents. These different excitability
properties destine the two types for distinct functions, because the former is essentially
silenced during realistic 8-15 Hz oscillations. By contrast, the general intrinsic
excitability, morphology and gene-profiles of the two types were surprisingly similar.
Even the expression of Kv4.3 channels were comparable, despite evidences showing that
Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing
phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary
subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms
of two previously unknown types of CCK+INs and demonstrate that alternative splicing
of few genes, which may be viewed as a minor change in the cells' whole transcriptome,
can determine cell-type identity.
