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This work tests the hypothesis that the cerebellum is critical to the perception of the timing of sensory events. Auditory tasks were used to assess two types of timing in a group of patients with a stereotyped specific degeneration of the cerebellum: the analysis of single time intervals requiring absolute measurements of time, and the holistic analysis of rhythmic patterns based on relative measures of time using an underlying regular beat. The data support a specific role for the cerebellum only in the absolute timing of single subsecond intervals but not in the relative timing of rhythmic sequences with a regular beat. The findings support the existence of a stopwatch-like cerebellar timing mechanism for absolute intervals that is distinct from mechanisms for entrainment with a regular beat. human | perception | absolute | relative | subsecond doi/ 10.1073/pnas.0910473107

Male mosquitoes detect flying females using antennal hearing organs sensitive to nanoscale mechanical displacements and that harbor motile mechanosensory neurons. The mechanisms supporting neuronal motility, and their function in peripheral sensory processing, remain, however, puzzling. The mechanical and neural responses reveal a transition that unmasks the onset of synchronization between sensory neurons. This synchronization constitutes an unconventional, mechanically driven, process of communication between sensory neurons. Enhancing auditory sensitivity and selectivity, synchronization between mechanosensors in the mosquito arises from entrainment to twice-frequency forcing and is formally analogous to injection-locking in high-power laser technology. This discovery opens up the enticing possibility that other sensory systems, even nonsensory cell ensembles, coordinate their actions through mechanical signaling. bioacoustics | entrainment | mosquito audition | nonlinear hearing

Hemispheric asymmetries of speech and music processing might arise from more basic specializations of left and right auditory cortex (AC). It is not clear, however, whether such asymmetries are unique to humans, i.e., consequences of speech and music, or whether comparable lateralized AC functions exist in nonhuman animals, as evolutionary precursors. Here, we investigated the cortical lateralization of perception of linearly frequency-modulated (FM) tones in gerbils, a rodent species with human-like low-frequency hearing. Using a footshock-reinforced shuttle-box avoidance go/no-go procedure in a total of 178 gerbils, we found that (i) the discrimination of direction of continuous FM (rising versus falling sweeps, 250-ms duration) was impaired by right but not left AC lesions; (ill the discrimination of direction of segmented FM (50-ms segments, 50-ms silent gaps, total duration 250 ms) was impaired by bilateral but not unilateral AC lesions; (iii) the discrimination of gap durations (10-30 ms) in segmented FM was impaired by left but not right AC lesions. AC lesions before and after training resulted in similar effects. Together, these experiments suggest that right and left AC, even in rodents, use different strategies in analyzing FM stimuli. Thus, the right AC, by using global cues, determines the direction of continuous and segmented FM but cannot discriminate gap durations. The left AC, by using local cues, discriminates gap durations and determines FM direction only when additional segmental information is available. asymmetry | lateralization | rodents

The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification. cochlear amplification | mechanosensory | prestin

We used both structural and functional brain imaging techniques to investigate the neural basis of absolute pitch (AP), a specialized skill present in some musicians. By using positron emission tomography, we measured cerebral blood flow during the presentation of musical tones to AP possessors and to control musicians without AP. Listening to musical tones resulted in similar patterns of increased cerebral blood flow in auditory cortical areas in both groups, as expected. The AP group also demonstrated activation of the left posterior dorsolateral frontal cortex, an area thought to be related to learning conditional associations. However, a similar pattern of left dorsolateral frontal activity was also observed in non-AP subjects when they made relative pitch judgments of intervals, such as minor or major. Conversely, activity within the right inferior frontal cortex was observed in control but not in AP subjects during the interval-judgment task, suggesting that AP possessors need not access working memory mechanisms in this task. MRI measures of cortical volume indicated a larger left planum temporale in the AP group, which correlated with performance on an pitch-naming task. Our findings suggest that AP may not be associated with a unique pattern of cerebral activity but rather may depend on the recruitment of a specialized network involved in the retrieval and manipulation of verbal-tonal associations.

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8 [degrees] for 20-30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.

Visual memory for scenes is surprisingly robust. We wished to examine whether an analogous ability exists in the auditory domain. Participants listened to a variety of sound clips and were tested on their ability to distinguish old from new clips. Stimuli ranged from complex auditory scenes (e.g., talking in a pool hall) to isolated auditory objects (e.g., a dog barking) to music. In some conditions, additional information was provided to help participants with encoding. In every situation, however, auditory memory proved to be systematically inferior to visual memory. This suggests that there exists either a fundamental difference between auditory and visual stimuli, or, more plausibly, an asymmetry between auditory and visual processing.

Auditory conditioning (associative learning) causes reorganization of the cochleotopic (frequency) maps of the primary auditory cortex (Al) and the inferior colliculus. Focal electric stimulation of the Al also evokes basically the same cortical and collicular reorganization as that caused by conditioning. Therefore, part of the neural mechanism for the plasticity of the central auditory system caused by conditioning can be explored by focal electric stimulation of the Al. The reorganization is due to shifts in best frequencies (BFs) together with shifts in frequency-tuning curves of single neurons. In the Al of the Mongolian gerbil (Meriones unguiculatus) and the posterior division of the Al of the mustached bat (Pteronotus parnelli), focal electric stimulation evokes BF shifts of cortical auditory neurons located within a 0.7-mm distance along the frequency axis. The amount and direction of BF shift differ depending on the relationship in BF between stimulated and recorded neurons, and between the gerbil and mustached bat. Comparison in BF shift between different mammalian species and between different cortical areas of a single species indicates that BF shift toward the BF of electrically stimulated cortical neurons (centripetal BF shift) is common in the Al, whereas BF shift away from the BF of electrically stimulated cortical neurons (centrifugal BF shift) is special. Therefore, we propose a hypothesis that reorganization, and accordingly organization, of cortical auditory areas caused by associative learning can be quite different between specialized and nonspecialized (ordinary) areas of the auditory cortex. bat | gerbil | hearing | reorganization of cortex | tonotopic map

We report the cloning and characterization of rat [Alpha]10, a previously unidentified member of the nicotinic acetylcholine receptor (nAChR) subunit gene family. The protein encoded by the [Alpha]10 nAChR subunit gene is most similar to the rat [Alpha]9 nAChR, and both [Alpha]9 and [Alpha]10 subunit genes are transcribed in adult rat mechanosensory hair cells. Injection of Xenopus laevis oocytes with [Alpha]10 cRNA alone or in pairwise combinations with either [Alpha]2-[Alpha]6 or [Beta]2-[Beta]4 subunit cRNAs yielded no detectable ACh-gated currents. However, coinjection of [Alpha]9 and [Alpha]10 cRNAs resulted in the appearance of an unusual nAChR subtype. Compared with homomeric [Alpha]9 channels, the [Alpha]9[Alpha]10 nAChR subtype displays faster and more extensive agonist-mediated desensitization, a distinct currentvoltage relationship, and a biphasic response to changes in extracellular [Ca.sup.2+] ions. The pharmacological profiles of homomeric [Alpha]9 and heteromeric [Alpha]9[Alpha]10 nAChRs are essentially indistinguishable and closely resemble those reported for endogenous cholinergic eceptors found in vertebrate hair cells. Our data suggest that efferent modulation of hair cell function occurs, at least in part, through heteromeric nAChRs assembled from both [Alpha]9 and [Alpha]10 subunits.

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel 'what' and 'where' processing by the primate visual cortex. If 'where' information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

Neuronal models predict that retrieval of specific event information reactivates brain regions that were active during encoding of this information. Consistent with this prediction, this positron-emission tomography study showed that remembering that visual words had been paired with sounds at encoding activated some of the auditory brain regions that were engaged during encoding. After word-sound encoding, activation of auditory brain regions was also observed during visual word recognition when there was no demand to retrieve auditory information. Collectively, these observations suggest that information about the auditory components of multisensory event information is stored in auditory responsive cortex and reactivated at retrieval, in keeping with classical ideas about 'redintegration,' that is, the power of part of an encoded stimulus complex to evoke the whole experience.

Investigations using hippocampal slices maintained in vitro have demonstrated that bursts of oscillatory field potentials in the gamma frequency range (30-80 Hz) are followed by a slower oscillation in the beta 1 range (12-20 Hz). In this study, we demonstrate that a comparable gamma-to-beta transition is seen in the human electroencephalogram (EEG) in response to novel auditory stimuli. Correlations between gamma and beta I activity revealed a high degree of interdependence of synchronized oscillations in these bands in the human EEG. Evoked (stimulus-locked) gamma oscillations preceded beta 1 oscillations in response to novel stimuli, suggesting that this may be analogous to the gamma-to-beta shift observed in vitro. Beta 1 oscillations were the earliest discriminatory responses to show enhancement to novel stimuli, preceding changes in the broad-band event-related potential (mismatch negativity). Later peaks of induced beta activity over the parietal cortex were always accompanied by an underlying gamma frequency oscillation as seen in vitro. A further analogy between in vitro and human recordings was that both gamma and beta oscillations habituated markedly after the initial novel stimulus presentation.

We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system that is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency that depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies that span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions that regulate the motor protein activity. By controlling the bundle's propensity to oscillate, this feedback automatically maintains the system in the operating regime where it is most sensitive to sinusoidal stimuli. The model explains how hair cells can detect sounds that carry less energy than the background noise.