Calcium-dependent persistent facilitation of spike backpropagation in the CA1 pyramidal neurons

Sodium-dependent action potentials initiated near the soma are known to bac kpropagate over the dendrites of CA1 pyramidal neurons in an activity-depen dent manner. Consequently, later spikes in a train have smaller amplitude w hen recorded in the apical dendrites. We found that depolarization and resu ltant Ca2+ influx into dendrites caused a persistent facilitation of spike backpropagation. Dendritic patch recordings were made from CA1 pyramidal ne urons in mouse hippocampal slices under blockade of fast excitatory and inh ibitory synaptic inputs. Trains of 10 backpropagating action potentials ind uced by antidromic stimulation showed a clear decrement in the amplitude of later spikes when recorded in the middle apical dendrites. After several d epolarizing current pulses, the amplitude of later spikes increased persist ently, and all spikes in a train became almost equal in size. BAPTA (10 mM) contained in the pipette or low-Ca2+ perfusing solution abolished this dep olarization-induced facilitation, indicating that Ca2+ influx is required. This facilitation was present in G alpha(q) knock-out mice that lack the pr eviously reported muscarinic receptor-mediated enhancement of spike backpro pagation. Therefore, these two forms of facilitation are clearly distinct i n their intracellular mechanisms. Intracellular injection of either calmodu lin binding domain (100 mu M) or Ca2+/calmodulin-kinase II (CaMKII) inhibit or 281-301 (10 mu M) blocked the depolarization-induced facilitation. Bath application of a membrane-permeable CaMKII inhibitor KN-93 (10 mu M) also b locked the facilitation, but KN-92 (10 mu M), an inactive isomer of KN-93, had no effect. These results suggest that increases in [Ca2+](i) cause pers istent facilitation of spike backpropagation in the apical dendrite of CA1 pyramidal neuron by CaMKII-dependent mechanisms.