Cholecystokinin action on layer 6b neurons in somatosensory cortex

Layer 6b in neocortex is a distinct sublamina at the ventral portion of layer 6. Corticothalamic projections arise from 6b neurons, but few studies have examined the functional properties of these cells. In the present study we examined the actions of cholecystokinin (CCK) on layer 6b neocortical neurons using whole-cell patch clamp recording techniques. We found that the general CCK receptor agonist CCK8S (sulfated CCK octapeptide) strongly depolarized the neurons, and this action persisted in the presence of tetrodotoxin, suggesting a postsynaptic site of action. The excitatory actions of CCK8S were mimicked by the selective CCKB receptor agonist CCK4, and attenuated by the selective CCKB receptor antagonist L365260, indicating a role for CCKB receptors. Voltage-clamp recordings revealed that CCK8S produced a slow inward current associated with a decreased conductance with a reversal potential near the K+ equilibrium potential. In addition, intracellular cesium also blocked the inward current, suggesting the involvement of a K+ conductance, likely Kleak. Our data indicate that CCK, acting via CCKB receptors, produces a long-lasting excitation of layer 6b neocortical neurons, and this action may play a critical role in modulation of corticothalamic circuit activity.