William E. O’Neill

Early bilateral deafening prevents calretinin up-regulation in the dorsal cortex of the inferior colliculus of aged CBA/CaJ mice

This study was conducted to test the hypothesis that age-related calretinin (CR) up-regulation seen in the dorsal cortex of the inferior colliculus (ICdc) of old hearing CBA mice is dependent upon neural activity within the auditory pathway. We tested this hypothesis by bilaterally deafening young CBA/CaJ mice with kanamycin, and then aging them until 24 months. This manipulation mimics the lack of sound-evoked auditory activity experienced by old C57BL/6J mice, who are deaf and do not show CR up-regulation with age. Cell counts revealed that the density of CR+ cells in the ICdc of old hearing CBA mice was statistically different from old deafened CBA mice raised under identical conditions. Old hearing CBAs possessed an average of 27.54 more CR+ cells/100 microm2 than old deafened CBAs. When old deafened CBAs were compared to young hearing CBAs, young hearing C57s, and old deaf C57s, there was no significant difference in mean CR+ cell density in ICdc. Thus, only the old normal hearing CBAs showed an increase in CR+ cells with age, supporting the hypothesis that CR up-regulation depends upon sound-evoked activity. Moreover, these results demonstrate that up-regulation of CR expression was not simply due to a mouse strain difference.

Age-related Decline in Kv3.1b Expression in the Mouse Auditory Brainstem Correlates with Functional Deficits in the Medial Olivocochlear Efferent System

MARTHA L. ZETTEL, XIAOXIA ZHU, WILLIAM E. O_NEILL, AND ROBERT D. FRISINA Department of Otolaryngology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642-8629, USA Department of Neurobiology and Anatomy, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA Center for Navigation and Communication Sciences, University of Rochester, Rochester, NY 14642, USA Department of Brain and Cognitive Sciences, College of Arts, Sciences and Engineering, University of Rochester, Rochester, NY 14642, USA International Center for Hearing and Speech Research, National Technical Institute for the Deaf, Rochester Institute of Technology, Rochester, NY 14623, USA

The effects of early bilateral deafening on calretinin expression in the dorsal cochlear nucleus of aged CBA/CaJ mice.

The aim of this study was to test the hypothesis that calretinin (CR) levels in the aged mouse auditory brainstem depend upon hearing ability. Old animals with good hearing, and thus higher sound-evoked activity levels, were predicted to have higher levels of CR immunoreactivity than old animals with hearing loss. CR immunoreactivity was analyzed in the deep layer (layer III) of the dorsal cochlear nucleus (DCN) in CBA/CaJ mice that were bilaterally deafened at 3 months of age with kanamycin, and then aged until 24 months. This manipulation partially mimics the lack of sound-evoked auditory activity experienced by old C57BL/6J mice, who are deaf at 24 months of age (but show residual hearing at 15 months) and have lower levels of CR immunoreactivity than old CBA mice with normal hearing [Hear. Res. 158 (2001) 131]. Cell counts revealed that the density of CR+ cells in DCN layer III of the deafened CBA mice was statistically different from old intact CBA mice raised under identical conditions. Old deafened CBAs showed a decline of 47% in the mean density of CR+ cells compared to old hearing CBAs, thus supporting the hypothesis. Interestingly, while there tended to be fewer CR+ cells in the old deaf C57s as compared to young C57s and young and old CBAs with normal hearing, the difference was not statistically significant. It is possible that the residual hearing of C57 mice at 15 months may provide sufficient auditory input to maintain CR at levels higher than CBA mice that are deafened completely at 3 months of age, and are profoundly deaf for a much longer time (21 months).

Active behavioral coping alters the behavioral but not the endocrine response to stress

Exposure to traumatic stressors typically causes lasting changes in emotionality and behavior. However, coping strategies have been shown to prevent and alleviate many stress consequences and the biological mechanisms that underlie coping are of great interest. Whereas the laboratory stressor inescapable tail-shock induces anxiety-like behaviors, here we demonstrate that permitting a rat to chew on a wooden dowel during administration of tail-shock prevented the development of anxiety like behaviors in the open field and juvenile social exploration tests. Uncontrollable stressors increase corticosterone and decrease thyroid hormone, and we hypothesized that coping would blunt these changes. While tail-shock did produce these effects, active coping did not alter hormone levels. The dissociation between behavioral resilience and circulating hormones is discussed with regard to the utility of these molecules as biomarkers for psychiatric disease.

Patterned tone sequences reveal non-linear interactions in auditory spectrotemporal receptive fields in the inferior colliculus.

Linear measures of auditory receptive fields do not always fully account for a neurons response to spectrotemporally-complex signals such as frequency-modulated sweeps (FM) and communication sounds. A possible source of this discrepancy is cross-frequency interactions, common response properties which may be missed by linear receptive fields but captured using two-tone masking. Using a patterned tonal sequence that included a balanced set of all possible tone-to-tone transitions, we have here combined the spectrotemporal receptive field with two-tone masking to measure spectrotemporal response maps (STRM). Recording from single units in the mustached bat inferior colliculus, we found significant non-linear interactions between sequential tones in all sampled units. In particular, tone-pair STRMs revealed three common features not visible in linear single-tone STRMs: 1) two-tone facilitative interactions, 2) frequency-specific suppression, and 3) post-stimulatory suppression in the absence of spiking. We also found a correlative relationship between these nonlinear receptive field features and sensitivity for different rates and directions of FM sweeps, dynamic features found in many vocalizations, including speech. The overwhelming prevalence of cross-frequency interactions revealed by this technique provides further evidence of the central auditory systems role as a pattern-detector, and underscores the need to include nonlinearity in measures of the receptive field.

Thalamic projections to the auditory cortex in the rufous horseshoe bat (Rhinolophus rouxi)

In this study, we analyzed the thalamic connections to the parietal or dorsal auditory cortical fields of the horseshoe bat, Rhinolophus rouxi. The data of the present study were collected as part of a combined investigation of physiologic properties, neuroarchitecture, and chemoarchitecture as well as connectivity of cortical fields in Rhinolophus, in order to establish a neuroanatomically and functionally coherent view of the auditory cortex. Horseradish peroxidase or wheat-germ-agglutinated horseradish peroxidase deposits were made into cortical fields after mapping response properties. The dorsal fields of the auditory cortex span nearly the entire parietal region and comprise more than half of the nonprimary auditory cortex. In contrast to the temporal fields of the auditory cortex, which receive input mainly from the ventral medial geniculate body (or “main sensory nucleus”), the dorsal fields of the auditory cortex receive strong input from the “associated nuclei” of the medial geniculate body, especially from the anterior dorsal nucleus of the medial geniculate body. The anterior dorsal nucleus is as significant for the dorsal fields of the auditory cortex as the ventral nucleus of the medial geniculate body is for the temporal fields of the auditory cortex. Additionally, the multisensory nuclei of the medial geniculate body provide a large share of the total input to the nonprimary fields of the auditory cortex. Comparing the organization of thalamic auditory cortical afferents in Rhinolophus with other species demonstrates the strong organizational similarity of this bat’s auditory cortex with that of other mammals, including primates, and provides further evidence that the bat is a relevant and valuable model for studying mammalian auditory function.

Eye position and cross-sensory learning both contribute to prism adaptation of auditory space.

Optical prisms shift visual space, and through adaptation over time, generate a compensatory realignment of sensory-motor reference frames. In humans, prism-induced lateral shifts of visual space produce a corresponding shift in sound localization. We recently reported that sound localization shifts towards eccentric eye position, approaching approximately 40% of gaze over several minutes. Given that eye position affects sound localization directly, prism adaptation may well reflect contributions of both eye position and sensory adaptation; while the visual world is shifted by the prisms, the eyes must also shift simply to gaze ahead. To test this new concept of prism adaptation, 10 young (18-27 year) adults localized sound targets before and after 4 h of adaptation to base-right or base-left prisms that induced an 11.4 degrees shift left or right, respectively. In separate sessions subjects were exposed to: (1) natural binaural hearing; (2) diotically presented inputs devoid of meaningful spatial cues; or (3) attenuated hearing to simulate hearing loss. These preliminary results suggest that the prism adaptation of auditory space is dependent on two independent influences: (1) the effect of displaced mean eye position induced by the prisms, which occurs without cross-sensory experience; and (2) true cross-sensory learning in response to an imposed offset between auditory and visual space.

The Central Control of Biosonar Signal Production in Bats Demonstrated by Microstimulation of Anterior Cingulate Cortex in the Echolocating Bat, Pteronotus Parnelli Parnelli

One of the ultimate goals of sensory neurobiology is to understand how sensory feedback controls subsequent motor behavior. For both auditory and speech scientists, it is of particular interest to know how auditory information influences vocalizations, and conversely how vocalization affects auditory processing. Such questions have an important bearing on both the vocal behavior of the mature organism, and the acquisition of vocal repertoires in the young during development. In many vertebrate species, communication sounds are learned from a combination of exposure to the sounds produced by adults, listening to self-vocalized sounds, and laryngeal and orofacial motor feedback. Thus there is a feedback loop established which involves learning a model of the signal via auditory stimulation, subsequent attempts to duplicate the model vocally, and comparison of the resulting vocalization with the internalized model again via auditory analysis. This process has been well documented for the learning of species-specific song patterns in many songbirds (Konishi and Nottebohm 1969; Marler and Peters 1977), and is thought to guide the development of human speech patterns (Marler 1976).

Advancing age alters the influence of eye position on sound localization

Vision and audition provide spatial information about the environment to guide natural behavior. Because the eyes move in the head while the ears remain head-fixed, input conveying eye position in the head is required to maintain audiovisual congruence. Human perception of auditory space was previously shown to shift with changes in eye position, regardless of the target’s frequency content and spatial cues underlying horizontal and vertical localization. In this study, we examined whether this interaction is altered by advancing age. Head-restrained young (18–44 yo), middle-aged (45–64 yo), and elderly (65–81 yo) human subjects localized noise bursts under conditions of transient and sustained ocular deflection. All three age groups demonstrated a time-dependent shift of auditory space in the direction of eye position. Moreover, this adaptation showed a clear decline with advancing age, but only for peripheral auditory space (beyond ±10° from midline). Alternatively, adaptation in the periphery may occur, but is more sluggish than in the central field and therefore not fully observed in this experiment. The age-dependent effect cannot be readily explained by senescent peripheral hearing loss, suggesting a change in central processing of auditory space in relation to the control of gaze.

Processing of Paired Biosonar Signals in the Cortices of Rhinolophus Rouxi and Pteronotus P. Parnellii: A Comparative Neurophysiological and Neuroanatomical Study

The old world horseshoe bat, Rhinolophus rouxi, and the new world mustached bat, Pteronotus p. parnellii, belong phylogenetically to different bat families. On the other hand they share similar types of echolocation calls, both using long constant frequency (CF) pulses terminated by a downward frequency sweep (FM). The behavioural strategies of the two species also show striking resemblences in that they both are compensating for frequency shifts introduced into the echo by the Doppler effect when flying, and they are known to hunt for prey preferably in acoustically dense and cluttered surroundings. Suga, O’Neill and coworkers have studied in detail the auditory cortex of Pteronotus and especially the processing of paired biosonar signals in this area (for review: Suga, this volume). They found at least three cortical fields in which neurons could only be stimulated if the two stimuli satisfied distinct spectral and temporal conditions (CF/CF-, FM/FM-fields and the dorsal fringe area). These specialized cortical fields lie dorsal and dorsoanterior to the tonotopically organized primary auditory cortex. Paired stimuli have not been used previously in the auditory cortex of Rhinolophus and therefore no equivalent information is available in this species.