Calcium-Dependent Persistent Facilitation of Spike Backpropagation in the CA1 Pyramidal Neurons

Abstract

Sodium-dependent action potentials initiated near the soma are known to backpropagate over the dendrites of CA1 pyramidal neurons in an activity-dependent manner. Consequently, later spikes in a train have smaller amplitude when recorded in the apical dendrites. We found that depolarization and resultant Ca²⁺ influx into dendrites caused a persistent facilitation of spike backpropagation. Dendritic patch recordings were made from CA1 pyramidal neurons in mouse hippocampal slices under blockade of fast excitatory and inhibitory synaptic inputs. Trains of 10 backpropagating action potentials induced by antidromic stimulation showed a clear decrement in the amplitude of later spikes when recorded in the middle apical dendrites. After several depolarizing current pulses, the amplitude of later spikes increased persistently, and all spikes in a train became almost equal in size. BAPTA (10 mM) contained in the pipette or low-Ca^(2+) perfusing solution abolished this depolarization-induced facilitation, indicating that Ca²⁺ influx is required. This facilitation was present in Gα_q knock-out mice that lack the previously reported muscarinic receptor-mediated enhancement of spike backpropagation. Therefore, these two forms of facilitation are clearly distinct in their intracellular mechanisms. Intracellular injection of either calmodulin binding domain (100 μM) or Ca²⁺/calmodulin-kinase II (CaMKII) inhibitor 281–301 (10 μM) blocked the depolarization-induced facilitation. Bath application of a membrane-permeable CaMKII inhibitor KN-93 (10 μM) also blocked the facilitation, but KN-92 (10 μM), an inactive isomer of KN-93, had no effect. These results suggest that increases in [Ca²⁺)]_i cause persistent facilitation of spike backpropagation in the apical dendrite of CA1 pyramidal neuron by CaMKII-dependent mechanisms.

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