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The electrogenesis of synaptically activated dendritic Ca2+-mediated potentials, which may contribute to synaptic signal integration in pyramidal cells, was examined in rat layers V–VI prefrontal cortical (PFC) neurons in vitro. Intrasomatically recorded suprathreshold synaptic responses evoked by stimulation of the distal dendrites were attenuated by focal Cd2+ application to the proximal apical dendritic stem (100–200 μm from soma), but not to the apical dendritic tuft (>500 μm from soma). With use of intracellular QX-314 and Cs+ to block Na+ and K+ currents, intrasomatic recordings revealed that the Cd2+-induced attenuation of synaptic responses was attributable to the blockade of a dendritic Ca2+-mediated “hump” potential and high-threshold Ca2+ spike activated by NMDA EPSPs. The hump potential was not blocked by bath application of Ni2+ (100 μm) but was blocked by focal application of Cd2+ to the proximal but not distal apical dendrites, suggesting that it was generated by Ca2+ channels located in the proximal dendrites. Direct patch-clamp recordings made from the distal apical tuft of layers V–VI PFC neurons revealed that layers I–II synaptic stimulation or intradendritic depolarizing current pulses evoked tetrodotoxin- and QX-314-sensitive Na+ spikes. Unlike in the stem of the apical dendrite, Ca2+spikes were not easily evoked in the distal apical tuft when Na+ channels were blocked. When triggered, the Cd2+-sensitive Ca2+ spikes in the dendritic tuft were nonregenerative and had very high activation thresholds (approximately +10 mV). These results suggested that the high voltage-activated Ca2+ potentials that amplify distal EPSPs are primarily generated in the proximal stem of the apical dendrite and not within the fine dendritic branches of the apical tuft of layers V–VI PFC neurons.

Contributions of Voltage-Gated Ca2+Channels in the Proximal versus Distal Dendrites to Synaptic Integration in Prefrontal Cortical Neurons

Contributions of Voltage-Gated Ca²⁺Channels in the Proximal versus Distal Dendrites to Synaptic Integration in Prefrontal Cortical Neurons