Auditory Neurophysiology publications

We reconstructed the intrinsic axons of 32 neurons in the guinea pig inferior colliculus (IC) following juxtacellular labeling. Biocytin was injected into cells in vivo , after first analyzing physiological response properties. Based on axonal morphology there were two classes of neuron: (1) laminar cells (14/32, 44%) with an intrinsic axon and flattened dendrites confined to a single fibrodendritic lamina and (2) translaminar cells (18/32, 56%) with axons that terminated in two or more laminae in the central nucleus (ICc) or the surrounding cortex. There was also one small, low-frequency cell with bushy-like dendrites that was very sensitive to interaural timing differences. The translaminar cells were subdivided into three groups of cells with: (a) stellate dendrites that crossed at least two laminae (8/32, 25%); (b) flattened dendrites confined to one lamina and that had mainly en passant axonal swellings (7/32, 22%) and (c) short, flattened dendrites and axons with distinctive clusters of large terminal boutons in the ICc (3/32, 9%). These terminal clusters were similar to those of cortical basket cells. The 14 laminar cells all had sustained responses apart from one offset response. Almost half the non-basket type translaminar cells (7/15) had onset responses while the others had sustained responses. The basket cells were the only ones to have short-latency (7–9 ms), chopper responses and this distinctive temporal response should allow them to be studied in more detail in future. This is the first description of basket cells in the auditory brainstem, but more work is required to confirm their neurotransmitter and precise post-synaptic targets.

Auditory nerve single-unit recordings were obtained from two groups of young barn owls (age, between posthatching days 11 and 86) in terminal experiments under two different anesthetic regimes: ketamine (6-11 mg/kg) plus xylazine (∼2 mg/kg); or isoflurane (1-1.5%) in oxygen, delivered via artificial respiration. In a second series of minimally invasive experiments, auditory brainstem responses (ABRs) were recorded in the same four adult barn owls (Tyto alba; age, between 5 and 32 months) under three different anesthetic protocols: ketamine (10 mg/kg) plus xylazine (3 mg/kg), isoflurane (1-1.5%), and sevoflurane (2-3%) in carbogen. Finally, the ABR measurements on adult owls were repeated in terminal experiments including more invasive procedures such as artificial respiration and higher isoflurane dosage. The main finding was a significant deterioration of auditory sensitivity in barn owls under gas anesthesia, at the level of the auditory nerve (i.e., a very peripheral level of the auditory system). The effect was drastic in the young animals that experienced threshold elevations in auditory nerve single-unit responses of ≥20 dB. ABR thresholds assessed repeatedly in experiments on adult owls were also significantly higher under isoflurane and sevoflurane, on average by 7 and 15 dB, compared with ketamine/xylazine. This difference already occurred with minimal dosages and was reversibly enlarged with increased isoflurane concentration. Finally, there was evidence for confounding detrimental effects associated with artificial respiration over many hours, which suggested oxygen toxicity.

Auditory stream segregation describes the way that sounds are perceptually segregated into groups or streams on the basis of perceptual attributes such as pitch or spectral content. For sequences of pure tones, segregation depends on the tones' proximity in frequency and time. In the auditory cortex (and elsewhere) responses to sequences of tones are dependent on stimulus conditions in a similar way to the perception of these stimuli. However, although highly dependent on stimulus conditions, perception is also clearly influenced by factors unrelated to the stimulus, such as attention. Exactly how 'bottom-up' sensory processes and non-sensory 'top-down' influences interact is still not clear. Here, we recorded responses to alternating tones (ABAB …) of varying frequency difference (FD) and rate of presentation (PR) in the auditory cortex of anesthetized guinea-pigs. These data complement previous studies, in that top-down processing resulting from conscious perception should be absent or at least considerably attenuated. Under anesthesia, the responses of cortical neurons to the tone sequences adapted rapidly, in a manner sensitive to both the FD and PR of the sequences. While the responses to tones at frequencies more distant from neuron best frequencies (BFs) decreased as the FD increased, the responses to tones near to BF increased, consistent with a release from adaptation, or forward suppression. Increases in PR resulted in reductions in responses to all tones, but the reduction was greater for tones further from BF. Although asymptotically adapted responses to tones showed behavior that was qualitatively consistent with perceptual stream segregation, responses reached asymptote within 2 s, and responses to all tones were very weak at high PRs (>12 tones per second). A signal-detection model, driven by the cortical population response, made decisions that were dependent on both FD and PR in ways consistent with perceptual stream segregation. This included showing a range of conditions over which decisions could be made either in favor of perceptual integration or segregation, depending on the model 'decision criterion'. However, the rate of 'build-up' was more rapid than seen perceptually, and at high PR responses to tones were sometimes so weak as to be undetectable by the model. Under anesthesia, adaptation occurs rapidly, and at high PRs tones are generally poorly represented, which compromises the interpretation of the experiment. However, within these limitations, these results complement experiments in awake animals and humans. They generally support the hypothesis that 'bottom-up' sensory processing plays a major role in perceptual organization, and that processes underlying stream segregation are active in the absence of attention.

Conspecific communication calls can be rhythmic or contain extended, discontinuous series of either constant or frequency modulated harmonic tones and noise bursts separated by brief periods of silence. In the guinea pig, rhythmic calls can produce isomorphic responses within the primary auditory cortex (AI) where single units respond to every call element. Other calls such as the chutter comprise a series of short irregular syllables that vary in their spectral content and are more like human speech. These calls can also evoke isomorphic responses, but may only do so in fields in the auditory belt and not in AI. Here we present evidence that cells in AI treat the individual elements within a syllable as separate auditory objects and respond selectively to one or a subset of them. We used a single chutter exemplar to compare single/multi-unit responses in the low-frequency portion of AI-AI(LF) and the low-frequency part of the thalamic medial geniculate body-MGB(LF) in urethane anaesthetized guinea pigs. Both thalamic and cortical cells responded with brief increases in firing rate to one, or more, of the 8 main elements present in the chutter call. Almost none of the units responded to all 8 elements. While there were many different combinations of responses to between one and five of the elements, MBG(LF) and AI(LF) neurons exhibited the same specific types of response combinations. Nearby units in the upper layers of the cortex tended to respond to similar combinations of elements while the deep layers were less responsive. Thus, the responses from a number of AI units would need to be combined in order to represent the entire chutter call. Our results don't rule out the possibility of constructive convergence but there was no evidence that a convergence of inputs within AI led to a complete representation of all eight elements.

The central nucleus of the inferior colliculus (IC) is organized into a series of fibro-dendritic laminae, orthogonal to the tonotopic progression. Many neurons have their dendrites confined to one lamina while others have dendrites that cross over a number of laminae. Here, we have used juxtacellular labeling in urethane anesthetized guinea pigs to visualize the cells with biocytin and have analyzed their response properties, in order to try and link their structure and function. Out of a sample of 38 filled cells, 15 had dendrites confined within the fibro-dendritic laminae and in 13 we were also able to reconstruct their local axonal tree. Based on dendritic morphology they were subdivided into flat or less flat; small, medium, or large; elongated or disk-shaped cells. Two of the elongated cells had many dendritic spines while the other cells had few or none. Twelve of the cells had their local axonal tree restricted to the same lamina as their dendrites while one cell had its dendrites in a separate lamina from the axon. The axonal plexus was more extensive (width 0.7-1.4 mm) within the lamina than the dendrites (width generally 0.07-0.53 mm). The intrinsic axons were largely confined to a single lamina within the central nucleus, but at least half the cells also had output axons with two heading for the commissure and five heading into the brachium. We were able to identify similarities in the physiological response profiles of small groups of our filled cells but none appeared to represent a homogeneous morphological cell type. The only common feature of our sample was one of exclusion in that the onset response, a response commonly recorded from IC cells, was never seen in laminar cells, but was in cells with a stellate morphology. Thus cells with laminar dendrites have a wide variety of physiological responses and morphological subtypes, but over 90% have an extensive local axonal tree within their local lamina.

We investigated how physiologically observed forward suppression interacts with stimulus frequency in neuronal responses in the guinea pig auditory cortex. The temporal order and frequency proximity of sounds influence both their perception and neuronal responses. Psychophysically, preceding sounds (conditioners) can make successive sounds (probes) harder to hear. These effects are larger when the two sounds are spectrally similar. Physiological forward suppression is usually maximal for conditioner tones near to a unit's characteristic frequency (CF), the frequency to which a neuron is most sensitive. However, in most physiological studies, the frequency of the probe tone and CF are identical, so the role of unit CF and probe frequency cannot be distinguished. Here, we systemically varied the frequency of the probe tone, and found that the tuning of suppression was often more closely related to the frequency of the probe tone than to the unit's CF, i.e. suppressed tuning was specific to probe frequency. This relationship was maintained for all measured gaps between the conditioner and the probe tones. However, when the probe frequency and CF were similar, CF tended to determine suppressed tuning. In addition, the bandwidth of suppression was slightly wider for off-CF probes. Changes in tuning were also reflected in the firing rate in response to probe tones, which was maximally reduced when probe and conditioner tones were matched in frequency. These data are consistent with the idea that cortical neurons receive convergent inputs with a wide range of tuning properties that can adapt independently.

The directionality of hair cell stimulation combined with the vibration of the basilar membrane causes the auditory nerve fiber action potentials, in response to low-frequency stimuli, to occur at a particular phase of the stimulus waveform. Because direct mechanical measurements at the cochlear apex are difficult, such phase locking has often been used to indirectly infer the basilar membrane motion. Here, we confirm and extend earlier data from mammals using sine wave stimulation over a wide range of sound levels (up to 90 dB sound pressure level). We recorded phase-locked responses to pure tones over a wide range of frequencies and sound levels of a large population of auditory nerve fibers in the anesthetized guinea pig. The results indicate that, for a constant frequency of stimulation, the phase lag decreases with increases in the characteristic frequency (CF) of the nerve fiber. The phase lag decreases up to a CF above the stimulation frequency, beyond which it decreases at a much slower rate. Such phase changes are consistent with known basal cochlear mechanics. Measurements from individual fibers showed smaller but systematic variations in phase with sound level, confirming previous reports. We found a "null" stimulation frequency at which little variation in phase occurred with sound level. This null frequency was often not at the CF. At stimulation frequencies below the null, there was a progressive lag with sound level and a progressive lead for stimulation frequencies above the null. This was maximally 0.2 cycles.