Topographically organized maps of the sensory receptor epithelia are regarded as cornerstones of cortical organization as well as valuable readouts of diverse biological processes ranging from evolution to neural plasticity. However, maps are most often derived from multiunit activity recorded in the thalamic input layers of anesthetized animals using near-threshold stimuli. Less distinct topography has been described by studies that deviated from the formula above, which brings into question the generality of the principle. Here, we explicitly compared the strength of tonotopic organization at various depths within core and belt regions of the auditory cortex using electrophysiological measurements ranging from single units to delta-band local field potentials (LFP) in the awake and anesthetized mouse. Unit recordings in the middle cortical layers revealed a precise tonotopic organization in core, but not belt, regions of auditory cortex that was similarly robust in awake and anesthetized conditions. In core fields, tonotopy was degraded outside the middle layers or when LFP signals were substituted for unit activity, due to an increasing proportion of recording sites with irregular tuning for pure tones. However, restricting our analysis to clearly defined receptive fields revealed an equivalent tonotopic organization in all layers of the cortical column and for LFP activity ranging from gamma to theta bands. Thus, core fields represent a transition between topographically organized simple receptive field arrangements that extend throughout all layers of the cortical column and the emergence of non-tonotopic representations outside the input layers that are further elaborated in the belt fields.

Usher syndrome type IIA (USH2A), characterized by progressive photoreceptor degeneration and congenital moderate hearing loss, is the most common subtype of Usher syndrome. In this article, we show that the USH2A protein, also known as usherin, is an exceptionally large (Ϸ600-kDa) matrix protein expressed specifically in retinal photoreceptors and developing cochlear hair cells. In mammalian photoreceptors, usherin is localized to a spatially restricted membrane microdomain at the apical inner segment recess that wraps around the connecting cilia, corresponding to the periciliary ridge complex described for amphibian photoreceptors. In sensory hair cells of the cochlea, it is associated transiently with the hair bundles during postnatal development. Targeted disruption of the Ush2a gene in mice leads to progressive photoreceptor degeneration and a moderate but nonprogressive hearing impairment, mimicking the visual and hearing deficits in USH2A patients. These data suggest that usherin is required for the long-term maintenance of retinal photoreceptors and for the development of cochlear hair cells. We propose a model in which usherin in photoreceptors is tethered via its C terminus to the plasma membrane and its large extracellular domain projecting into the periciliary matrix, where they may interact with the connecting cilium to fulfill important structural or signaling roles.photoreceptor degeneration ͉ retina ͉ retinitis pigmentosa

Neurons in the lateral superior olive (LSO) compute sound location based on differences in interaural intensity, coded in ascending signals from the two cochleas. Unilateral destruction of the neuronal feedback from the LSO to the cochlea, the lateral olivocochlear efferents, disrupted the normal interaural correlation in response amplitudes to sounds of equal intensity. Thus, lateral olivocochlear feedback maintains the binaural balance in neural excitability required for accurate localization of sounds in space.The olivocochlear efferent pathway has two major subsystems (Fig. 1a,b): a medial (MOC) component of myelinated fibers projecting to the cochlea's outer hair cells and a lateral (LOC) component of unmyelinated fibers projecting to cochlear nerve fibers, near their afferent synapses with cochlear inner hair cells 1 . The MOC system is a cholinergic sound-evoked feedback loop, which, when activated, raises cochlear thresholds by decreasing the contributions of electro-motile outer hair cells to the normal amplification of sound-induced vibration of the cochlear epithelium. The LOC system is cytochemically heterogeneous, with cholinergic, GABAergic, dopaminergic and peptidergic transmission. It comprises at least two subgroups: when activated, it elicits either slow (τ ∼ 10 min) excitation or slow suppression of cochlear nerve output 2 .To isolate LOC contributions to cochlear function, we stereotaxically lesioned the LSO unilaterally (right side) in mice (age 6-8 weeks) by injection of a neurotoxin (melittin3) and assessed effects bilaterally by physiological measures of cochlear neural excitability and outer hair cell function, 2 and 4 weeks later. The lesions were assessed double-blind in two ways ( Fig. 1): (1) lesion location in serial brainstem sections stained for cholinergic markers and (2) density of olivocochlear efferent terminals in outer hair cell and inner hair cell areas in immunostained cochleas (Supplementary Methods online). Because LOC projections are almost exclusively to the ipsilateral inner hair cell area (Fig. 1a,b), when the injection successfully targeted the LSO (Fig. 1d), the cochlea on the injected side showed loss of cholinergic terminals in the inner hair cell area (Fig. 1f), without a change in cholinergic terminals on outer hair cells in either ear (Fig. 1e,f). Based on this combined central and peripheral assessment, we concluded that, of the 36 mice that survived the initial surgery and all subsequent electrophysiological testing, 20 were at least partial 'hits' and 16 were complete 'misses'. In most miss cases, there was no lesion, suggesting that the injection pipet clogged. In one hit and one miss case, there was minor damage to the MOC system, as evidenced by proximity of the lesion to their cells of origin and by a just-detectable decrease in cholinergic terminals in the outer hair cell area.To evaluate the effects of selective LOC de-efferentation, we took two measures of cochlear function 4 . The first, auditory brainstem response (ABR), constitutes the sum...