Action Potential Modulation in CA1 Pyramidal Neuron Axons Facilitates OLM Interneuron Activation in Recurrent Inhibitory Microcircuits of Rat Hippocampus

Oriens-lacunosum moleculare (O-LM) interneurons in the CA 1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA 1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA 1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outside-out patch recordings from CA 1 pyramidal neuron axons revealed a high density of alpha-dendrotoxin (alpha-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA 1 pyramidal neurons and O-LM interneurons. CA 1 pyramidal neuron-O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by alpha-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA 1 pyramidal neuron axons substantially enhances the efficacy of principal neuroninterneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits.