What’s a cerebellar circuit doing in the auditory system?The DCN has a laminar, cerebellum-like organizationSynapses in the superficial DCN are adjustableDCN neurons convey information related to sound localizationA cerebellum-like function for the DCN?ReferencesWhat’s a cerebellar circuit doing in theauditory system?Donata Oertel1and Eric D. Young21Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA2Department of Biomedical Engineering, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USAThe shapes of the head and ears of mammals are asym-metrical top-to-bottom and front-to-back. Reflections ofsounds from these structures differ with the angle ofincidence, producing cues for monaural sound localiz-ation in the spectra of the stimuli at the eardrum. Neu-rons in the dorsal cochlear nucleus (DCN) respondspecifically to spectral cues and integrate them withsomatosensory, vestibular and higher-level auditoryinformation through parallel fiber inputs in a cerebel-lum-like circuit. Synapses between parallel fibers andtheir targets show long-term potentiation (LTP) andlong-term depression (LTD), whereas those betweenauditory nerve fibers and their targets do not. Thispaper discusses the integration of acoustic and theproprioceptive information in terms of possible compu-tational roles for the DCN.Hearing enables vertebrate animals to know what goes onaround them even when they cannot see. Localizing theposition of sound sources is thus an important biologicalfunction of the auditory system. Interaural time andintensity differences are used by reptiles, birds andmammals for localizing sounds in the horizontal plane[1]. However, these cues are not useful for localizingsounds in the vertical plane (i.e. low–high, front–back) orwhen hearing is lost in one ear. For vertical localization,mammals use spectral cues – modifications in the spectrathat are produced by the interactions of sound with theexternal ear, or pinna. These modifications vary as afunction of the direction from which sound emanates, sothat the frequency content of the sound reaching theeardrum provides a cue for source location [2 –4] (Box 1). Inthe cat, the dorsal cochlear nucleus (DCN) has been shownto be important for behavioral processing of spectrallocalization cues [5,6]. The cells whose axons conveysignals from the DCN to the inferior colliculus provide aspecific representation of these acoustic cues and integratethem with somatosensory information about the positionor movement of the ears.The DCN has a laminar, cerebellum-like organizationThe output axons of the DCN originate from fusiform andgiant cells (Figure 1). These cells integrate activity fromtwo systems of inputs, auditory nerve fibers and parallelfibers. Auditory nerve fibers bring acoustic informationfrom the cochlea to smooth dendrites in the deep layer ofthe DCN [7]. Parallel fibers, the unmyelinated axons ofgranule cells, contact spines on dendrites of fusiform, giantand cartwheel cells in the superficial layer of the DCN [8].Granule cells convey information they receive from wide-spread areas of the brain that are associated with multiplesensory modalities. Inputs to the granule cell area arisefrom the dorsal column nuclei [9], vestibular afferents [10],pontine nuclei [11], unmyelinated auditory nerve fibers[12], the octopus cell area of the ventral cochlear nucleus(VCN) [13], the inferior colliculus [14] and the auditorycortex [15].The superficial layers of the DCN share many featureswith the overlying cerebellum (Figure 1); most import-antly, both structures contain granule cells and associatedinterneurons. Cochlear nuclear and cerebellar granulecells develop from a common population of neurons [16].Granule cells lie in clusters around the VCN and in thefusiform cell layer of the DCN [8]. Like the vestibulocere-bellum, the DCN contains unipolar brush cells [17], Golgicells [18] and superficial stellate cells [19].Cartwheel cells are interneurons that occupy a similarposition in the DCN circuit to that occupied by Purkinjecells in the cerebellum [20]. The two cells contain many ofthe same proteins and are similarly affected by geneticmutations [21], and both fire complex action potentials[19,22]. Unlike Purkinje cells, cartwheel cells terminatelocally, contacting other cartwheel, fusiform and giantcells, and receive no input like that from climbing fibers.Although cartwheel cells contain GABA and glutamic aciddecarboxylase, they are glycinergic [23].Largely because of their granule cell systems, the DCNand the octavolateral nuclei in weakly electric fish areconsidered to be ‘cerebellum-like’ nuclei [24,25]. Likefusiform and giant cells of the DCN, the principal cells ofthese nuclei receive granule cell inputs on one set ofdendrites and primary sensory inputs on another.Synapses in the superficial DCN are adjustableThe strength of synapses between parallel fibers and theirtargets in the DCN, but not that of synapses betweenauditory nerve fibers and their targets, is modulated byactivity (Figure 2) [26]. In fusiform and cartwheel cells,pairing of postsynaptic depolarization with stimulation ofthe parallel fibers in the molecular layer at high frequency(100 Hz) increases the amplitude of the synaptic current.After the high-frequency shocks, short-term potentiationCorresponding author: Donata Oertel ([email protected]).Review TRENDS in Neurosciences Vol.27 No.2 February 2004www.sciencedirect.com 0166-2236/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tins.2003.12.001decreases over several minutes, leaving long-term poten-tiation (LTP). Stimulation at low frequency (1 Hz) pro-duces long-term depression (LTD) of the synaptic currentin both fusiform and cartwheel cells. Stimulation ofauditory nerve fibers in the deep layer evokes synapticresponses in fusiform cells but those synaptic responsesshow no plasticity.Postsynaptic intracellular buffering of Ca2þpreventsLTP and LTD in fusiform and cartwheel cells, indicatingthat plasticity is initiated postsynaptically and involveschanges in intracellular Ca2þlevels. Postsynaptic changesin intracellular Ca2þconcentration following parallel fiberstimulation are initiated by activation of neurotransmitterreceptors and are mediated through signaling pathwaysthat differ in fusiform and cartwheel cells (Table 1) [26].Although AMPA receptors are activated by parallel fibers[27], these