SEARCH

SEARCH BY CITATION

Keywords:

  • hyperpolarization-activated cyclic-nucleotide-gated type 1 channels;
  • hyperpolarization-activated current;
  • lateral superior olive;
  • superior olivary complex;
  • synchronous excitatory post-synaptic potential

Abstract

We have previously shown that mice lateral superior olive (LSO) neurons exhibit a large hyperpolarization-activated current (Ih), 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 Ih 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 Ih present in both the soma and dendrites (control) with LSO neurons without Ih (blocked with ZD7288) and with LSO neurons with Ih only present peri-somatically (ZD7288+ computer-simulated Ih using a dynamic clamp). LSO neurons without Ih had a wider time window for firing in response to inputs with short time separations. Simulated somatic Ih (dynamic clamp) could not reverse this effect. Blocking Ih 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 Ih could not abolish a ZD7288-induced increase of responsiveness to widely separated excitatory inputs. Using a compartmental LSO model, we show that dendritic Ih can reduce EPSP integration by locally decreasing the input resistance. Our results suggest a significant role for dendritic Ih in LSO neurons, where the activation/deactivation of Ih can alter the LSO response to synaptic inputs.