In Vivo Dynamic Clamp Study of I_h in the Mouse Inferior Colliculus

Abstract

Nagtegaal AP, Borst JG. In vivo dynamic clamp study of I h in the mouse inferior colliculus. J Neurophysiol 104: 940 -948, 2010. First published June 10, 2010 doi:10.1152/jn.00264.2010. Approximately half of the cells in the mouse inferior colliculus have the hyperpolarization-activated mixed cation current I h , yet little is known about its functional relevance in vivo. We therefore studied its contribution to the processing of sound information in single cells by making in vivo whole cell recordings from the inferior colliculus (IC) of young-adult anesthetized C57Bl/6 mice. Following pharmacological block of the endogenous channels, a dynamic clamp approach allowed us to study the responses to current injections or auditory stimuli in the presence and absence of I h within the same neuron, thus avoiding network or developmental effects. The presence of I h changed basic cellular properties, including depolarizing the resting membrane potential and decreasing resting membrane resistance. Sound-evoked excitatory postsynaptic potentials were smaller but at the same time reached a more positive membrane potential when I h was present. With I h , a subset of cells showed rebound spiking following hyperpolarizing current injection. Its presence also changed more complex cellular properties. It decreased temporal summation in response to both hyperpolarizing and depolarizing repetitive current stimuli, and resulted in small changes in the cycle-averaged membrane potential during sinusoidal amplitude modulated (SAM) tones. Furthermore, I h minimally decreased the response to a tone following a depolarization, an effect that may make a small contribution to forward masking. Our results thus suggest that previously observed differences in IC cells are a mixture of direct effects of I h and indirect effects due to the change in membrane potential or effects due to the co-expression with other channels.

Ih Equalizes Membrane Input Resistance in a Heterogeneous Population of Fusiform Neurons in the Dorsal Cochlear Nucleus

“…I h was built on a previous description of the current (Nagtegaal and Borst, 2010). We used two activation variables ( A h1 and A h2 ) that were described with same steady state dynamics ( A h ∞ ) (Leao et al, 2012) but different voltage dependence of time constant (τ h1 and τ h2 ).…”

Potassium conductance dynamics confer robust spike-time precision in a neuromorphic model of the auditory brain stem

“…In theory, this prediction could be confirmed experimentally using in vivo patch clamp during acoustic stimulation, with local application of dendrotoxin to block g KL and dynamic clamp to introduce a static leak (e.g., Nagtegaal and Borst 2010). A slightly less challenging experimental confirmation would use in vitro patch clamp, again with dendrotoxin and dynamic clamp; however, in this case the dynamic clamp would additionally be used to introduce synthetic synaptic conductances generated from an established auditory nerve model (e.g., Prinz et al 2003b).…”

“…Our results indicate that if the single input spikes more than once per stimulus cycle, g KL could suppress a response to the subsequent, off-phase spikes. Furthermore, these single synaptic inputs are composed of multiple coordinated but independent readily releasable vesicles (Borst and Sakmann 1996;Neef et al 2007) with a heterogeneous distribution of release times (Meinrenken et al 2002;Wittig and Parsons 2008), which essentially increases the number of functional inputs to within the range observed for bushy cells.…”

A neural mechanism of phase-locked responses to sinusoidally amplitude-modulated signals in the inferior colliculus

“…They suggested the possibility that complement of voltagesensitive ion channels in ICc neurons acts to restrict the phaselocking to low SAM frequencies. There is evidence that dynamic properties of ICc neurons are determined by several ion channels expressed in membrane (Sirvaramakrishnan and Oliver, 2001;Koch and Grothe, 2003;Nagtegaal and Borst, 2010). However, it remains unclear which types of ion channels limit the phase-locking to low SAM frequencies.…”

“…The inhibition induced by the inhibitory effect reproduces the response profiles of onset and non-onset PL neurons and contributes to the increased values of VS in these neurons. Several ion channels have been found to be involved in the cellular dynamics of IC neurons in mammalian brain (Sirvaramakrishnan and Oliver, 2001;Koch and Grothe, 2003;Nagtegaal and Borst, 2010). The hyperpolarization-activated mixed cation current I h contributes to different firing pattern of IC neurons (Koch and Groth, 2003;.…”