Publications using TDT

Learning involves not only the establishment of memory per se, but also the specific details of its contents. In classical conditioning, the former concerns whether an association was learned while the latter discloses what was learned. The neural bases of associativity have been studied extensively while neural mechanisms of memory specificity have been neglected. Stimulation of the cholinergic nucleus basalis (NBs) paired with a preceding tone induces CS-specific associative memory. As different levels of acetylcholine may be released naturally during different learning situations, we asked whether the level of activation of the cholinergic neuromodulatory system can control the degree of detail that is encoded and retrieved. Adult male rats were tested pre- and post-training for behavioral responses (interruption of ongoing respiration) to tones of various frequencies (1-15 kHz, 70 dB, 2 s). Training consisted of 200 trials/day of tone (8.0 kHz, 70 dB, 2 s) either paired or unpaired with NBs (CS-NBs = 1.8 s) at moderate (65.7+/-9.0 microA, one day) or weak (46.7+/-12.1 microA, three training days) levels of stimulation, under conditions of controlled behavioral state (pre-trial stable respiration rate). Post-training (24 h) responses to tones revealed that moderate activation induced both associative and CS-specific behavioral memory, whereas weak activation produced associative memory lacking frequency specificity. The degree of memory specificity 24 h after training was positively correlated with the magnitude of CS-elicited increase in gamma activity within the EEG during training, but only in the moderate NBs group. Thus, a low level of acetylcholine released by the nucleus basalis during learning is sufficient to induce associativity whereas a higher level of release enables the storage of greater experiential detail. gamma waves, which are thought to reflect the coordinated activity of cortical cells, appear to index the encoding of CS detail. The findings demonstrate that the amount of detail in memory can be directly controlled by neural intervention.

The olivocochlear efferent system is both cholinergic and GABAergic and innervates sensory cells and sensory neurons of the inner ear. Cholinergic effects on cochlear sensory cells are well characterized, both in vivo and in vitro ; however, the robust GABAergic innervation is poorly understood. To explore the functional roles of GABA in the inner ear, we characterized the cochlear phenotype of seven mouse lines with targeted deletion of a GABA A receptor subunit (α1, α2, α5, α6, β2, β3, or δ). Four of the lines (α1, α2, α6, and δ) were normal: there was no cochlear histopathology, and cochlear responses suggested normal function of hair cells, afferent fibers, and efferent feedback. The other three lines (α5, β2, and β3) showed threshold elevations indicative of outer hair cell dysfunction. α5 and β2 lines also showed decreased effects of efferent bundle activation, associated with decreased density of efferent terminals on outer hair cells: although the onset of this degeneration was later in α5 (>6 weeks) than β2 (<6 weeks), both lines shows normal efferent development (up to 3 weeks). Two lines (β2 and β3) showed signs of neuropathy, either decreased density of afferent innervation (β3) or decreased neural responses without concomitant attenuation of hair cell responses (β2). One of the lines (β2) showed a clear sexual dimorphism in cochlear phenotype. Results suggest that the GABAergic component of the olivocochlear system contributes to the long-term maintenance of hair cells and neurons in the inner ear.

Hippocampal sharp waves (SPWs) are among the earliest neural population patterns observed in infant mammals. Similarly, startles are among the earliest behavioral events observed. Here we provide evidence indicating that these two events are linked mechanistically soon after birth in freely moving and head‐fixed 1 to 4‐day‐old rats. EMG electrodes and intrahippocampal silicon depth electrodes were used to detect the presence of startles and SPWs, respectively. In intact pups, the majority of sharp waves were preceded by startles (average latency: 161 ms). When the hippocampal formation was surgically separated from the brainstem, however, sharp waves and startles still occurred, but now independently. In addition, unrelated to startles or SPWs, gamma oscillations were detected in several subjects, as were neocortical “spindles” that propagated passively into the hippocampus. The cooccurrence of sharp waves and startles provides the opportunity for Hebbian changes in synaptic efficacy and, thus, is poised to contribute to the assembly of neural circuits early in development. © 2006 Wiley‐Liss, Inc.

The sound localization abilities of three rhesus monkeys were tested under head-restrained and head-unrestrained conditions. Operant conditioning and the magnetic search coil technique were used to measure eye and head movements to sound sources. Whereas the results support previous findings that monkeys localize sounds very poorly with their heads restrained, the data also reveal for the first time that monkeys localize sounds much more accurately and with less variability when their heads are allowed to move. Control experiments using acoustic stimuli known to produce spatial auditory illusions such as summing localization confirmed that the monkeys based their orienting on localizing the sound sources and not on remembering spatial locations that resulted in rewards. Overall, the importance of using ecologically valid behaviors for studies of sensory processes is confirmed, and the potential of the rhesus monkey, the model closest to human, for studies of spatial auditory function, is established.

Female hormone influences on auditory system aging are not completely understood. Because of widespread clinical use of hormone replacement therapy (HRT), it is critical to understand HRT effects on sensory systems. The present study retrospectively analyzed and compared hearing abilities among 124 postmenopausal women taking HRT, treated with estrogen and progestin (E+P; n = 32), estrogen alone (E; n = 30), and a third [non-hormone replacement therapy (NHRT; n = 62)] control group. Subjects were 60–86 years old and were matched for age and health status. All had relatively healthy medical histories and no significant noise exposure, middle-ear problems, or major surgeries. Hearing tests included pure-tone audiometry, tympanometry, distortion-product otoacoustic emissions (DPOAEs), transient otoacoustic emissions, and the hearing-in-noise test (HINT). The HINT tests for speech perception in background noise, the major complaint of hearing-impaired persons. Pure-tone thresholds in both ears were elevated (poorer) for the E+P relative to the E and control groups. For DPOAEs, the E+P group presented with lower (worse) levels than the E and control groups, with significant differences for both ears. For the HINT results, the E+P group had poorer speech perception than the E and control groups across all background noise speaker locations and in quiet. These findings suggest that the presence of P as a component of HRT results in poorer hearing abilities in aged women taking HRT, affecting both the peripheral (ear) and central (brain) auditory systems, and it interferes with the perception of speech in background noise.

Accurate sensory perception often depends on the independent encoding and subsequent integration of multiple stimulus attributes. In the weakly electric fish Eigenmannia , P- and T-type primary afferent fibers are specialized for encoding the amplitude and phase, respectively, of electrosensory stimuli. We used a stimulus estimation technique to quantify the ability of P- and T-units to encode random modulations in amplitude and phase. As expected, P-units exhibited a clear preference for encoding amplitude modulations, whereas T-units exhibited a clear preference for encoding phase modulations. Surprisingly, both types of afferents also encoded their nonpreferred stimulus attribute when it was presented in isolation or when the preferred stimulus attribute was sufficiently weak. Because afferent activity can be affected by modulations in either amplitude or phase, it is not possible to unambiguously distinguish between these two stimulus attributes by observing the activity of a single afferent fiber. Simple model neurons with a preference for encoding either amplitude or phase also encoded their nonpreferred stimulus attribute when it was presented in isolation, suggesting that such ambiguity is unavoidable. Using the well known jamming avoidance response as a probe of electrosensory perception, we show that the ambiguity at the single-neuron level gives rise to a systematic misrepresentation of stimuli at the population level and a resulting misperception of the amplitude and phase of electrosensory stimuli.

Hypoxia-ischemia (HI) is associated with premature birth, and injury during term birth. Many infants experiencing HI later show disruptions of language, with research suggesting that rapid auditory processing (RAP) deficits (i.e., impairment in the ability to discriminate rapidly changing acoustic signals), play a causal role in language problems. We recently bridged these lines of research by showing RAP deficits in rats with unilateral-HI injury induced on postnatal days 1, 7, or 10 (P1, P7, or P10. While robust RAP deficits were found in HI animals, it was suggested that our within-age sample size did not provide sufficient power to detect age-at-injury differences within the pooled HI group. The current study sought to examine differences in neuropathology and behavior following unilateral-HI injury on P1 versus P7 in rats. Ages chosen for HI induction reflect differential stages of neurodevelopmental maturity, and subsequent regional differences in vulnerability to reduced blood flow/oxygen (modeling age-related differences in premature/term HI injury). Results showed that during the juvenile period, both P1 and P7 HI groups exhibited significant RAP deficits, but deficits in the P1 HI group resolved with repeated testing (compared to shams), while P7 HI animals showed lasting deficits in RAP and spatial learning/memory through adulthood. The current findings are in accord with evidence that HI injury during different stages of developmental maturity (age-at-injury) leads to differential neuropathologies, and provide the novel observation that in rats, P1 versus P7 induced pathologies are associated with different patterns of auditory processing and learning/memory deficits across the lifespan.

The purpose of this paper is to introduce a new signal-processing strategy, spatiotemporal pattern correction (SPC), that is based on our knowledge of the level-dependent temporal response properties of auditory nerve fibers in normal and impaired ears. In normal-hearing listeners, tuning is sharp for low-level inputs and broadens as input level increases. When peripheral filters change their shape with input level, the phase properties of the filters and the latency of the filter’s response also change. However, in listeners with hearing loss, tuning is broad for both low- and high-level inputs. Thus, there is little change in the phase properties of the filters for different input levels. The SPC strategy manipulates the temporal aspects of different frequency channels of sounds in an attempt to “correct” for this abnormal spatiotemporal response pattern of the impaired ear. Quality judgments and intelligibility measures of speech processed at various SPC strengths were obtained from a small group of normal-hearing listeners and listeners with hearing loss. In general, listeners with hearing loss preferred sentences with some degree of SPC processing, whereas normal-hearing listeners preferred unprocessed sentences. Benefit from SPC on the nonsense syllable test varied greatly across phonemes and listeners. A more comprehensive study of listeners with different degrees and configurations of hearing loss is needed to determine the amount of SPC benefit.

An understanding of the auditory system's operation requires knowledge of the mechanisms underlying thresholds. In this work we compare detection thresholds obtained with a three-interval-three-alternative forced-choice paradigm with reaction thresholds extracted from both reaction probabilities (RP) and reaction times (RT) in a simple RT paradigm from the same listeners under otherwise nearly identical experimental conditions. Detection thresholds, RP, and RT to auditory stimuli exhibited substantial variation from session to session. Most of the intersession variation in RP and RT could be accounted for by intersession variation in a listener's absolute sensitivity. The reaction thresholds extracted from RP were very similar, if not identical, to those extracted from RT. On the other hand, reaction thresholds were always higher than detection thresholds. The difference between the two thresholds can be considered as the additional amount of evidence required by each listener to react to a stimulus in an unforced design on top of that necessary for detection in the forced-choice design. This difference is inversely related to the listener's probability of producing false alarms. We found that RT, once corrected for some irreducible minimum RT, reflects the time at which a given stimulus reaches the listener's reaction threshold. This suggests that the relationships between simple RT and loudness (reported in the literature) are probably caused by a tight relationship between temporal summation at threshold and temporal summation of loudness.

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 μM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

Hypothesized circuitry enabling behavioral memory formation can be tested by its direct activation in the absence of normal experience. Neuromodulation via the cortical release of acetylcholine by the nucleus basalis (NB) is hypothesized to be sufficient to induce specific, associative behavioral memory. Previously, we found that tone paired with stimulation of the nucleus basalis (NBs) for 3000 trials over 15 days induced such memory, supporting the hypothesis. However, as standard associative memory can be established much more rapidly, we asked whether NB-induced memory develops rapidly. Adult male Sprague-Dawley rats, trained and tested in the same calm, waking state, were divided into Paired (n=5) and control (n=4) groups, each of which received a single session of 200 trials of an 8.0 kHz conditioned stimulus (CS) either paired with NBs or with unpaired presentation of NBs. Respiration, cardiac activity, and evoked potentials in the primary auditory cortex (ACx) were recorded. Memory and its degree of specificity were assessed 24 h later by presenting tones of various frequencies (1-15 kHz) in the absence of NBs to yield behavioral frequency generalization gradients. Behavioral responses to test tones consisted of interruption of ongoing respiration and changes in heart rate. Post-training behavioral generalization gradients exhibited response peaks centered on the CS frequency for the Paired group alone. Tone evoked potentials from the ACx also developed CS-specific plasticity. The findings indicate that NB induction of specific behavioral associative memory, like normal memory, can develop rapidly and is accompanied by specific cortical plasticity, supporting the view that NB engagement during normal learning produces memory.

Background The common vampire bat Desmodus rotundus is one of three bat species that feed exclusively on the blood of mammals often more than 1000 times its size. Vampire bats even feed on human blood. Moreover, they tend to feed on the same individual over consecutive nights. Results Using psychoacoustical methods, we show that vampire bats can recognize individual humans by their breathing sounds. Accompanying psychoacoustical experiments using the same stimuli and procedure but with human listeners show that even these trained and instructed listeners were unable to achieve the vampire bats' performance under the most difficult conditions, where the breathing sounds had been recorded under physical strain. Conclusion It is suggested that vampire bats can make use of an individual acoustic signature imposed on breathing sounds in a way similar to that in which we identify humans by their vocalizations.

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

Large-conductance voltage- and Ca(2+)-activated K+ channels (BKCa) are involved in shaping spiking patterns in many neurons. Less is known about their role in mammalian inner hair cells (IHCs), mechanosensory cells with unusually large BKCa currents. These currents may be involved in shaping the receptor potential, implying crucial importance for the properties of afferent auditory signals. We addressed the function of BKCa by recording sound-induced responses of afferent auditory nerve (AN) fibers from mice with a targeted deletion of the pore-forming alpha-subunit of BKCa (BKalpha(-/-)) and comparing these with voltage responses of current-clamped IHCs. BKCa-mediated currents in IHCs were selectively abolished in BKalpha(-/-), whereas cochlear physiology was essentially normal with respect to cochlear sensitivity and frequency tuning.BKalpha(-/-) AN fibers showed deteriorated precision of spike timing, measured as an increased variance of first spike latency in response to tone bursts. This impairment could be explained by a slowed voltage response in the presynaptic IHC resulting from the reduced K+ conductance in the absence of BKCa. Maximum spike rates of AN fibers were reduced nearly twofold in BKalpha(-/-), contrasting with increased voltage responses of IHCs. In addition to presynaptic changes, which may be secondary to a modest depolarization of BKalpha(-/-) IHCs, this reduction in AN rates suggests a role of BKCa in postsynaptic AN neurons, which was supported by increased refractory periods. In summary, our results indicate an essential role of IHC BKCa channels for precise timing of high-frequency cochlear signaling as well as a function of BKCa in the primary afferent neuron.

One of the primary challenges that sensory systems face is extracting relevant information from background noise. In the auditory system, the ear receives efferent feedback, which may help it extract signals from noise. Here we directly test the hypothesis that efferent activity increases the signal-to-noise ratio (SNR) of the ear, using the relatively simple teleost ear. Tone-evoked saccular potentials were recorded before and after efferent stimulation, and the SNR of the responses was calculated. In quiet conditions, efferent stimulation suppressed saccular responses to a tone, reducing the SNR. However, when masking noise was added, efferent stimulation increased the SNR of the saccular responses within a range of stimulus combinations. These data demonstrate that auditory efferent feedback can increase SNR in conditions where a signal is masked by noise, thereby enhancing the encoding of signals in noise. Efferent feedback thus performs a fundamental signal processing function, helping the animal to hear sounds in difficult listening conditions.

Many previous studies have subdivided auditory neurons into a number of physiological classes according to various criteria applied to their binaural response properties. However, it is often unclear whether such classifications represent discrete classes of neurons or whether they merely reflect a potentially convenient but ultimately arbitrary partitioning of a continuous underlying distribution of response properties. In this study we recorded the binaural response properties of 310 units in the auditory cortex of anesthetized ferrets, using an extensive range of interaural level differences (ILDs) and average binaural levels (ABLs). Most recordings were from primary auditory fields on the middle ectosylvian gyrus and from neurons with characteristic frequencies >5 kHz. We used simple multivariate statistics to quantify a fundamental coding feature: the shapes of the binaural response functions. The shapes of all 310 binaural response surfaces were represented as points in a five-dimensional principal component space. This space captured the underlying shape of all the binaural response surfaces. The distribution of binaural level functions was not homogeneous because some shapes were more common than others. Despite this, clustering validation techniques revealed no evidence for the existence of discrete, or partially overlapping, clusters that could serve as a basis for an objective classification of binaural-level functions. We also examined the gradients of the response functions for the population of units; these gradients were greatest near the midline, which is consistent with free-field data showing that cortical neurons are most sensitive to changes in stimulus location in this region of space.

The extent to which context influences speech categorization can inform theories of pre-lexical speech perception. Across three conditions, listeners categorized speech targets preceded by speech context syllables. These syllables were presented as the sole context or paired with nonspeech tone contexts previously shown to affect speech categorization. Listeners’ context-dependent categorization across these conditions provides evidence that speech and nonspeech context stimuli jointly influence speech processing. Specifically, when the spectral characteristics of speech and nonspeech context stimuli are mismatched such that they are expected to produce opposing effects on speech categorization the influence of nonspeech contexts may undermine, or even reverse, the expected effect of adjacent speech context. Likewise, when spectrally matched, the cross-class contexts may collaborate to increase effects of context. Similar effects are observed even when natural speech syllables, matched in source to the speech categorization targets, serve as the speech contexts. Results are well-predicted by spectral characteristics of the context stimuli.

A recurring theme in theoretical work is that integration over populations of similarly tuned neurons can reduce neural noise. However, there are relatively few demonstrations of an explicit noise reduction mechanism in a neural network. Here we demonstrate that the brainstem of the barn owl includes a stage of processing apparently devoted to increasing the signal-to-noise ratio in the encoding of the interaural time difference (ITD), one of two primary binaural cues used to compute the position of a sound source in space. In the barn owl, the ITD is processed in a dedicated neural pathway that terminates at the core of the inferior colliculus (ICcc). The actual locus of the computation of the ITD is before ICcc in the nucleus laminaris (NL), and ICcc receives no inputs carrying information that did not originate in NL. Unlike in NL, the rate-ITD functions of ICcc neurons require as little as a single stimulus presentation per ITD to show coherent ITD tuning. ICcc neurons also displayed a greater dynamic range with a maximal difference in ITD response rates approximately double that seen in NL. These results indicate that ICcc neurons perform a computation functionally analogous to averaging across a population of similarly tuned NL neurons.

To study the possible involvement of energy-dependent mechanisms in the transduction of sound within the anuran ear, distortion product otoacoustic emissions (DPOAEs) were recorded in the northern leopard frog over a range of body temperatures. The effect of body temperature depended on the stimulus levels used and on the hearing organ under investigation. Low-level DPOAEs from the amphibian papilla (AP) were reversibly depressed for decreased body temperatures. Apparently, DPOAE generation in the AP depends on metabolic rate, indicating the involvement of active processes in the transduction of sound. In contrast, in the other hearing organ, the basilar papilla (BP), the effects of body temperature on DPOAEs were less pronounced, irrespective of the stimulus levels used. Apparently, metabolic rate is less influencing DPOAE generation. We interpret these results as evidence that no amplifier is involved in sound transduction in the BP. The passive functioning of the anuran BP would place this hearing organ in a unique position within tetrapod hearing, but may actually be beneficial to ectothermic species because it will provide the animal with a consistent spectral window, regardless of ambient or body temperature.

It has been suggested that “call-selective” neurons may play an important role in the encoding of vocalizations in primary auditory cortex (A1). For example, marmoset A1 neurons often respond more vigorously to natural than to time-reversed twitter calls, although the spectral energy distribution in the natural and time-reversed signals is the same. Neurons recorded in cat A1, in contrast, showed no such selectivity for natural marmoset calls. To investigate whether call selectivity in A1 can arise purely as a result of auditory experience, we recorded responses to marmoset calls in A1 of naive ferrets, as well as in ferrets that had been trained to recognize these natural marmoset calls. We found that training did not induce call selectivity for the trained vocalizations in A1. However, although ferret A1 neurons were not call selective, they efficiently represented the vocalizations through temporal pattern codes, and trained animals recognized marmoset twitters with a high degree of accuracy. These temporal patterns needed to be analyzed at timescales of 10–50 ms to ensure efficient decoding. Training led to a substantial increase in the amount of information transmitted by these temporal discharge patterns, but the fundamental nature of the temporal pattern code remained unaltered. These results emphasize the importance of temporal discharge patterns and cast doubt on the functional significance of call-selective neurons in the processing of animal communication sounds at the level of A1.