MOLECULAR AND SYNAPTIC MECHANISMS The hyperpolarization-activated non-specific cation current (I h ) adjusts the membrane properties, excitability, and activity pattern of the giant cells in the rat dorsal cochlear nucleus Zolt  an Ruszn  ak, 1,2 Bal  azs P  al, 2  Aron K } oszeghy, 2 Yuhong Fu, 1 G  eza Sz€ ucs 2 and George Paxinos 1,3 1 Neuroscience Research Australia, Sydney, NSW, 2031, Australia 2 Department of Physiology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary 3 School of Medical Science, The University of New South Wales, Sydney, NSW, 2052, Australia Keywords: developing auditory system, h-current, spontaneous activity, synaptic transmission, ZD7288 Abstract Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization-activated current in determining the activity of giant neurones in slices prepared from 10 to 14-day-old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)-sensitive inward current with a reversal potential and half-activation voltage of –36 and –88 mV, respectively. Consequently, the current was identified as the hyperpolar- ization-activated non-specific cationic current (I h ). At the resting membrane potential, 3.5% of the maximum I h conductance was available. Immunohistochemistry experiments suggested that hyperpolarization-activated, cyclic nucleotide-gated, cation non- selective (HCN)1, HCN2, and HCN4 subunits contribute to the assembly of the functional channels. Inhibition of I h hyperpolarized the membrane by 6 mV and impeded spontaneous firing. The frequencies of spontaneous inhibitory and excitatory postsynaptic currents reaching the giant cell bodies were reduced but no significant change was observed when evoked postsynaptic currents were recorded. Giant cells are affected by biphasic postsynaptic currents consisting of an excitatory and a subsequent inhibitory component. Inhibition of I h reduced the frequency of these biphasic events by 65% and increased the decay time constants of the inhibitory component. We conclude that I h adjusts the resting membrane potential, contributes to spontaneous action potential fir- ing, and may participate in the dendritic integration of the synaptic inputs of the giant neurones. Because its amplitude was higher in young than in adult rats, I h of the giant cells may be especially important during the postnatal maturation of the auditory system. Introduction The action potential firing pattern of the acoustic nerve contains all meaningful information about sound, including its frequency, inten- sity, and duration as well as the location of the sound source. The cochlear nucleus (CN) commences decoding the auditory informa- tion and passes its various components onto parallel channels that target higher auditory centres (e.g. Rhode & Greenberg, 1992; Romand & Avan, 1997; Rouiller, 1997). Although the details of this task are not fully understood, it is known that there are several cell types responsible for some special aspects of signal processing (e.g. Osen, 1969; Brawer et al., 1974). Most of these cells have charac- teristic morphology and membrane properties that subserve their tasks. A number of cell types in the CN (including bushy, octopus, and pyramidal cells) possess a current known as hyperpolarization- activated non-specific cationic current (I h ) (Bal & Oertel, 2000; Cut- tle et al., 2001; P al et al., 2003). I h was first noted in motoneurones (Araki et al., 1961), then it was described in cardiomyocytes (Brown et al., 1979; Brown & DiFrancesco, 1980) and photorecep- tors (Attwell & Wilson, 1980). I h is expressed in many parts of the auditory pathway, including the spiral ganglion (Chen, 1997; Mo & Davis, 1997; Szab o et al., 2002; Bakondi et al., 2009), trapezoid nucleus (Banks et al., 1993; Leao et al., 2005; Hassfurth et al., 2009), lateral superior olive (Leao et al., 2006; Hassfurth et al., 2009), dorsal nucleus of the lateral lemniscus (Fu et al., 1997), and inferior colliculus (Koch & Grothe, 2003). Giant cells make a significant contribution to the signal process- ing of the CN. They have far-reaching dendritic arborizations (Ostapoff et al., 1994) that allow them to receive information from many sources, including the parallel fibres formed by the axons of Correspondence: Zolt an Ruszn ak, 1 Neuroscience Research Australia, as above. E-mail: z.rusznak@neura.edu.au Received 29 May 2012, revised 19 November 2012, accepted 30 November 2012 © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, Vol. 37, pp. 876–890, 2013 doi:10.1111/ejn.12116 European Journal of Neuroscience