Modulation of dendritic synaptic processing in the lateral superior olive by hyperpolarization-activated currents

We have previously shown that mice lateral superior olive (LSO) neurons exhibit a large hyperpolarization-activated current (I-h), and that hyperpolarization-activated cyclic-nucleotide-gated type 1 channels are present in both the soma and dendrites of these cells. Here we show that the dendritic I-h in LSO neurons modulates the integration of multiple synaptic inputs. We tested the LSO neuron's ability to integrate synaptic inputs by evoking excitatory post-synaptic potentials (EPSPs) in conjunction with brief depolarizing current pulses (to simulate a second excitatory input) at different time delays. We compared LSO neurons with the native I-h present in both the soma and dendrites (control) with LSO neurons without I-h (blocked with ZD7288) and with LSO neurons with I-h only present peri-somatically (ZD7288+ computer-simulated I-h using a dynamic clamp). LSO neurons without I-h had a wider time window for firing in response to inputs with short time separations. Simulated somatic I-h (dynamic clamp) could not reverse this effect. Blocking I-h also increased the summation of EPSPs elicited at both proximal and distal dendritic regions, and dramatically altered the integration of EPSPs and inhibitory post-synaptic potentials. The addition of simulated peri-somatic I-h could not abolish a ZD7288-induced increase of responsiveness to widely separated excitatory inputs. Using a compartmental LSO model, we show that dendritic I-h can reduce EPSP integration by locally decreasing the input resistance. Our results suggest a significant role for dendritic I-h in LSO neurons, where the activation/deactivation of I-h can alter the LSO response to synaptic inputs.