Dynamic Interaction of Ih and IK-LVA during Trains of Synaptic Potentials in Principal Neurons of the Medial Superior Olive

Abstract

In neurons of the medial superior olive (MSO), voltage-gated ion channels control the submillisecond time resolution of binaural coincidence detection, but little is known about their interplay during trains of synaptic activity that would be experienced during auditory stimuli. Here, using modeling and patch-clamp recordings from MSO principal neurons in gerbil brainstem slices, we examined interactions between two major currents controlling subthreshold synaptic integration: a low voltage-activated potassium current (IK-LVA) and a hyperpolarization-activated cation current (Ih). Both Ih and IK-LVA contributed strongly to the resting membrane conductance, and during trains of simulated EPSPs exhibited cumulative deactivation and inactivation, respectively. In current-clamp recordings, regular and irregular trains of simulated EPSCs increased input resistance up to 60%, effects that accumulated and decayed (post-train) over hundreds of milliseconds. Surprisingly, the mean voltage and peaks of EPSPs increased by only a few millivolts during trains. Using a model of an MSO cell we demonstrated that the nearly uniform response during modest depolarizing stimuli relied on changes in Ih and IK-LVA, such that their sum remained nearly constant over time. Experiments and modeling showed that for simplified binaural stimuli (EPSC pairs in a noisy background) spike probability gradually increased in parallel with the increasing input resistance. Nevertheless, the interplay between Ih and IK-LVA helps to maintain a nearly uniform shape of individual synaptic responses, and we show that the time resolution of synaptic coincidence detection can be maintained during trains if EPSC size gradually decreases (as in synaptic depression), counteracting slow increases in excitability.

Subthreshold resonance properties contribute to the efficient coding of auditory spatial cues

“…Note that the hyperpolarization-activated current (I h ), which is responsible for resonances in many neurons in the central nervous system, also is highly expressed in principal MSO and LSO cells (37,38). However, its slow activation kinetics (∼100 ms), which would support resonances only at relatively low frequencies (∼10 Hz), means that it cannot account for the high resonant frequencies we report in this study, although I h may help maintain an operating voltage range so that resonance is preserved (39).…”

Combined application of brain-derived neurotrophic factor and neurotrophin-3 and its impact on spiral ganglion neuron firing properties and hyperpolarization-activated currents

“…As previously shown in SGNs, an elevation in cAMP shifts the voltage dependence of I h activation to more depolarized levels (Mo and Davis, 1997b;Yi et al, 2010). In addition, HCN channels and I h regulation has been linked with a number of interacting proteins and molecular factors such as TRIP8b, PIP2, protons, chloride, and tyrosine phosphorylation (Wahl-Schott and Biel, 2009), as well as the activity of voltagegated potassium channels (Cao and Oertel, 2011;George et al, 2009;Khurana et al, 2011;MacLean et al, 2003MacLean et al, , 2005. Further, neurotrophin-mediated regulation of I h has been demonstrated in respiratory neurons (Thoby-Brisson et al, 2003), whilst studies of central auditory nuclei show I h activity is altered in congenitallydeaf animals (Leao et al, 2005) and following sensory deprivation (Hassfurth et al, 2009).…”

Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive

“…They achieve this feat via an extremely precise coincidence detection mechanism (Goldberg and Brown 1969;Grothe and Sanes 1994;Yin and Chan 1990). This mechanism relies on the interaction between binaural excitatory and inhibitory inputs (Brand et al 2002;Pecka et al 2008), a subset of large cation conductances (Khurana et al 2011;Mathews et al 2010), and is thought to be strongly influenced by unique anatomical adaptations (Agmon-Snir et al 1998;Rautenberg et al 2009;Zhou et al 2005). Because of this tight structure-function relationship, a thorough survey of functional receptor and synaptic locations can provide insight into the in vivo behavior of MSO neurons and ultimately into ITD coding.…”