Single Unit publications

Perception of complex sounds depends on the encoding of the dynamic and static structures within the ongoing stimulus by the auditory system. Aging has been associated with deficits in both areas, thus, the difficulty that the elderly have in speech comprehension could due to hearing loss, or to a loss of temporal sensitivity, or some combination of both. We investigated the effects of sensorineural hearing loss (SNHL) on neural correlates of temporal resolution by recording the responses of inferior colliculus neurons to a gap detection paradigm. We used C57BL/6 (C57) strain of laboratory mouse, which carries the Ahl deafness gene that initiates a progressive high frequency SNHL beginning at about 2 months of age and rapidly progresses to total deafness by 18 months. We compared gap encoding from inferior collicular neurons from young, normal-hearing C57 mice and middle-aged, hearing-impaired, C57 mice, quantifying minimal gap threshold, and recovery functions. The proportion of unit types, spontaneous rates and degree of monotonicity were comparable between young and middle-aged C57 mice. As expected, single unit thresholds were elevated by 30-40 dB in middle-aged C57 mice. However, no significant differences in mean minimal gap thresholds or in the slopes of the gap recovery functions were found between the two age groups. Thus, the results suggest that moderate high frequency SNHL does not affect temporal processing as measured by the gap detection paradigm.

The clawed frog Xenopus laevis produces vocalizations consisting of distinct patterns of clicks. This study provides the first description of spontaneous, pure-tone and communication-signal evoked discharge properties of auditory nerve (n.VIII) fibers and dorsal medullary nucleus (DMN) cells in an obligatorily aquatic anuran. Responses of 297 n.VIII and 253 DMN units are analyzed for spontaneous rates (SR), frequency tuning, rate-intensity functions, and firing rate adaptation, with a view to how these basic characteristics shape responses to recorded call stimuli. Response properties generally resemble those in partially terrestrial anurans. Broad tuning exists across characteristic frequencies (CFs). Threshold minima are -101 dB re 1 mm/s at 675 Hz; -87 dB at 1,600 Hz; and -61 dB at 3,000 Hz (-90, -77, and -44 dB re 1 Pa, respectively), paralleling the peak frequency of vocalizations at 1.2-1.6 kHz with approximately 500 Hz in 3 dB bandwidth. SRs range from 0 to 80 (n.VIII) and 0 to 73 spikes/s (DMN). Nerve and DMN units of all CFs follow click rates in natural calls, < or =67 clicks/s and faster. Units encode clicks with a single spike, double spikes, or bursts. Spike times correlate closely with click envelopes. No temporal filtering for communicative click rates occurs in either n.VIII or the DMN.

Pretraining lesions of rat perirhinal cortex (PR) severely impair pavlovian fear conditioning to a 22 kHz ultrasonic vocalization (USV) cue. However, PR lesions are without significant effect when the cue is a continuous tone at the same or a lower frequency. Here we examined fear-conditioning-produced changes in single-unit firing elicited in rat PR by a 22 kHz tone cue or a 22 kHz USV cue. Chronic recording electrodes were introduced from the lateral surface of the skull. Altogether, 200 well isolated units were studied in 28 rats. Overall, 73% of the recorded single units (145 of 200 units) evidenced statistically significant firing changes in response to the tone or USV conditional stimulus (CS) after it had been paired several times with an aversive unconditional stimulus (US). Interestingly, 33% of units (66 of 200 units) that were initially CS-unresponsive became CS-responsive after conditioning. After conditioning, there were two notable differences between single-unit responses elicited by the USV cue and those elicited by the tone cue. First, 11% of the units (14 of 123 units) recorded from the USV-conditioned group displayed a precisely timed increase in firing rate during the 260 ms interval in which the US had previously occurred. This US-timed response was unique to the USV-conditioned group. Second, the mean latency of cue-elicited firing was ∼30 ms longer in the USV-conditioned group than in the tone-conditioned group. These cue-specific differences in acquired firing latencies and acquired firing patterns suggest that spectrotemporal properties of a CS can control the essential circuitry or neurophysiological mechanisms underlying fear conditioning.

During the second postnatal week in rats, the hippocampus exhibits a transient period of hyperexcitability. To systematically assess the relationship between the onset and end of this period and spontaneous hippocampal activity, we used silicon depth electrodes in unanaesthetized head‐fixed rats from postnatal day (P)2 to P18. At all ages, hippocampal sharp waves (SPWs) were prominent in the EEG. Beginning at P6, however, marked changes in SPWs and associated oscillations were detected. SPW‐related ‘gamma tails’ (60–100 Hz) and ‘ripples’ (140–200 Hz) were first observed at P6 and P7, respectively, and both oscillations persisted up to P18. Transiently, between P6 and P11, SPW duration decreased and the occurrence of SPW doublets increased. In addition, between P8 and P11, a subset of rats exhibited ‘spontaneous potentiated SPWs’ characterized by double polarity reversals, enhanced likelihood of gamma tails, and population spikes. Having identified a suite of transient hippocampal features consistent with a window of increased excitability, we next assessed whether electrographic seizure activity would be most easily induced during this period. To do this, kainic acid (KA; 200 ng/infusion) was infused into the hippocampus contralateral to the recording probe. KA did not induce seizure activity until P7 and reached peak effectiveness at P9. Thereafter, sensitivity to KA declined. All together, these findings provide in vivo neurophysiological support for the notion of a developmental window of heightened seizure susceptibility during the second postnatal week, and also suggest that spontaneous nonpathological hippocampal activity can be used to mark the onset and end of this period.

Space-specific neurons in the barn owl's auditory space map gain spatial selectivity through tuning to combinations of the interaural time difference (ITD) and interaural level difference (ILD). The combination of ITD and ILD in the subthreshold responses of space-specific neurons in the external nucleus of the inferior colliculus (ICx) is well described by a multiplication of ITD- and ILD-dependent components. It is unknown, however, how ITD and ILD are combined at the site of ITD and ILD convergence in the lateral shell of the central nucleus of the inferior colliculus (ICcl) and therefore whether ICx is the first site in the auditory pathway where multiplicative tuning to ITD- and ILD-dependent signals occurs. We used extracellular recording of single neurons to determine how ITD and ILD are combined in ICcl of the anesthetized barn owl ( Tyto alba). A comparison of additive, multiplicative, and linear-threshold models of neural responses shows that ITD and ILD are combined nonlinearly in ICcl, but the interaction of ITD and ILD is not uniformly multiplicative over the sample. A subset (61%) of the neural responses is well described by the multiplicative model, indicating that ICcl is the first site where multiplicative tuning to ITD- and ILD-dependent signals occurs. ICx, however, is the first site where multiplicative tuning is observed consistently. A network model shows that a linear combination of ICcl responses to ITD–ILD pairs is sufficient to produce the multiplicative subthreshold responses to ITD and ILD seen in ICx.

Rats emit ultrasonic vocalizations (USVs) as social signals in several situations. Lesion studies have shown that rat perirhinal cortex (PR), a polymodal sensory region that is reciprocally connected with the amygdala, is critical for normal fear conditioning to so-called "22 kHz USVs". Here we evaluated single-unit responses in rat PR to 22 kHz USVs and other acoustic stimuli. One question was whether PR circuits are specifically and preferentially tuned, prior to fear conditioning, to respond to USVs and USV-like stimuli. Two 22 kHz USVs were pre-recorded from different conspecifics. Each USV consisted of a "bout" of several discrete calls. Using experimentally naïve rats, single-unit responses to the USVs were compared with responses to continuous or discontinuous tones that had the same root frequency as the USVs (19 or 22 kHz). The on/off patterns of the discontinuous tones were temporally matched to the call structure in the corresponding USVs. Compared to continuous tones, the USVs were no more likely to elicit single-unit firing changes in PR. On the other hand, the continuous tones and USVs clearly did elicit different firing patterns in many units. More specifically, the USVs sometimes elicited a transient increase in discharge frequency to each call in a bout of calls. Interestingly, the USVs and the temporally matched tone segments usually elicited similar firing patterns. The USV-elicited firing pattern in PR thus appears to be controlled by the on/off temporal structure of the calls rather than by the frequency or amplitude modulations associated with each call in a bout of calls.

Disinhibition of the thalamus remains the primary model of information transfer between the basal ganglia and the cortex. Yet in apparent conflict with this model, the globus pallidus, a GABAergic basal ganglia output structure, often exhibits marked increases in firing rate during movement. To investigate the translation of pallidal activity and its relay through the thalamus, we explored a basal ganglia–thalamic pathway essential for song learning in songbirds. We found that single units in the thalamic nucleus DLM of urethane-anesthetized adult male zebra finches responded selectively to playback of the bird's own song, like neurons in its upstream and downstream nuclei. Because the pallidal input to these neurons forms giant calyx-like synapses, we were able to record extracellular signals from these presynaptic terminals as well. Pallidal units were distinctly excited by song playback, suggesting an increase in GABAergic transmission in the thalamus during sensory processing. However, this overall increased firing rate was phasic, punctuated by rapid decelerations in firing rate. In several cases, we were able to record presynaptic and postsynaptic units simultaneously. Correlating the presynaptic and postsynaptic activity, we found that disinhibition of thalamus may entail pallidal firing rate decelerations rather than simple long pauses in spontaneous activity, as has long been assumed.

Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli. However, whether this occurs in the context of natural communication, where stimulus significance is acquired through social interaction, has not been well investigated, perhaps because neural responses to species-specific vocalizations can be difficult to interpret within a systematic framework. The ultrasonic communication system between isolated mouse pups and adult females that either do or do not recognize the calls' significance provides an opportunity to explore this issue. We applied an information-based analysis to multi- and single unit data collected from anesthetized mothers and pup-naïve females to quantify how the communicative significance of pup calls affects their encoding in the auditory cortex. The timing and magnitude of information that cortical responses convey (at a 2-ms resolution) for pup call detection and discrimination was significantly improved in mothers compared to naïve females, most likely because of changes in call frequency encoding. This was not the case for a non-natural sound ensemble outside the mouse vocalization repertoire. The results demonstrate that a sensory cortical change in the timing code for communication sounds is correlated with the vocalizations' behavioral relevance, potentially enhancing functional processing by improving its signal to noise ratio.

Echolocating bats can identify three-dimensional objects exclusively through the analysis of acoustic echoes of their ultrasonic emissions. However, objects of the same structure can differ in size, and the auditory system must achieve a size-invariant, normalized object representation for reliable object recognition. This study describes both the behavioral classification and the cortical neural representation of echoes of complex virtual objects that vary in object size. In a phantom-target playback experiment, it is shown that the bat Phyllostomus discolor spontaneously classifies most scaled versions of objects according to trained standards. This psychophysical performance is reflected in the electrophysiological responses of a population of cortical units that showed an object-size invariant response (14/109 units, 13%). These units respond preferentially to echoes from objects in which echo duration (encoding object depth) and echo amplitude (encoding object surface area) co-varies in a meaningful manner. These results indicate that at the level of the bat's auditory cortex, an object-oriented rather than a stimulus-parameter-oriented representation of echoes is achieved.

Although NMDA receptors (NMDARs) are associated with synaptic plasticity, they form an essential part of responses to sensory stimuli. We compared contributions of glutamatergic NMDARs and AMPA receptors (AMPARs) to auditory responses in the inferior colliculus (IC) of awake, adult mustached bats. We examined the magnitude and temporal pattern of responses to tonal signals in single units before, during, and after local micro-iontophoretic application of selective antagonists to AMPARs [NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide)] and NMDARs [CPP ((±)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid)]. Combined blockade of AMPARs and NMDARs eliminated excitatory responses in nearly all neurons, whereas separate blockade of each receptor was quantitatively similar, causing substantial (>50%) spike reductions in ∼75% of units. The major result was that effects of receptor blockade were most closely related to the first-spike latency of a unit. Thus, AMPAR blockade substantially reduced spikes in all short-latency units (<12 ms) but never in long-latency units (≥12 ms). NMDAR blockade had variable effects on short-latency units but reduced spikes substantially for all long-latency units. There were no distinct contributions of AMPARs and NMDARs to early and late elements of responses. Thus, AMPAR blockade reduced early (onset) spikes somewhat more effectively than NMDAR blockade in short-latency units, but NMDAR blockade reduced onset spikes more effectively in long-latency units. AMPAR and NMDAR blockade were equally effective in reducing later elements of sustained responses in short-latency units, whereas NMDAR blockade was much more effective in long-latency units. These results indicate that NMDARs play multiple roles for signal processing in adult IC neurons.

Since its introduction in the early 1980s, the concept of a “preferred direction” for neuronal discharge has proven to be a powerful means of studying motor areas of the brain. In the current paper, we introduce the concept of a “muscle-space”–preferred direction (PD M ) that is analogous to the familiar hand-space–preferred direction (PD H ). PD M reflects the similarity between the discharge of a given neuron and the activity of each muscle in much the way that PD H reflects the similarity of discharge with motion along each of the three Cartesian coordinate axes. We used PD M to analyze the data recorded from neurons in the primary motor cortex (M1) of three different monkeys. The monkeys performed center-out movements within two different cubical workspaces centered either to the left or right of the monkey's shoulder while we simultaneously recorded neuronal discharge, muscle activity, and limb orientation. We calculated preferred directions in both hand space and muscle space, and computed the angles between these vectors under a variety of conditions. PDs for different neurons were broadly distributed throughout both hand space and muscle space, but the muscle-space vectors appeared to form clusters of functionally similar neurons. In general, repeated estimates of PD M were more stable over time than were similar estimates of PD H . Likewise, there was less change in PD M than in PD H for data recorded from the two different workspaces. However, although a majority of neurons had this muscle-like property, a significant minority was more stable in Cartesian hand space, reflecting a heterogeneity of function within M1.

Contemporary auditory prostheses ("cochlear implants") employ arrays of stimulating electrodes implanted in the scala tympani of the cochlea. Such arrays have been implanted in some 100,000 profoundly or severely deaf people worldwide and arguably are the most successful of present-day neural prostheses. Nevertheless, most implant users show poor understanding of speech in noisy backgrounds, poor pitch recognition, and poor spatial hearing, even when using bilateral implants. Many of these limitations can be attributed to the remote location of stimulating electrodes relative to excitable cochlear neural elements. That is, a scala tympani electrode array lies within a bony compartment filled with electrically conductive fluid. Moreover, scala tympani arrays typically do not extend to the apical turn of the cochlea in which low frequencies are represented. In the present study, we have tested in an animal model an alternative to the conventional cochlear implant: a multielectrode array implanted directly into the auditory nerve. We monitored the specificity of stimulation of the auditory pathway by recording extracellular unit activity at 32 sites along the tonotopic axis of the inferior colliculus. The results demonstrate the activation of specific auditory nerve populations throughout essentially the entire frequency range that is represented by characteristic frequencies in the inferior colliculus. Compared to conventional scala tympani stimulation, thresholds for neural excitation are as much as 50-fold lower and interference between electrodes stimulated simultaneously is markedly reduced. The results suggest that if an intraneural stimulating array were incorporated into an auditory prosthesis system for humans, it could offer substantial improvement in hearing replacement compared to contemporary cochlear implants.

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.

To examine possible neural strategies for the detection of tones in broadband noise, single-neuron extracellular recordings were obtained from the anteroventral cochlear nucleus (AVCN) in anesthetized gerbils. Detection thresholds determined by average discharge rate and several temporal metrics were compared with previously reported psychophysical detection thresholds in cats ( Costalupes 1985 ). Because of their limited dynamic range, the average discharge rates of single neurons failed to predict psychophysical detection thresholds for relatively high-level noise at all measured characteristic frequencies (CFs). However, temporal responses changed significantly when a tone was added to a noise, even for neurons with flat masked rate-level functions. Three specific temporal analyses were applied to neural responses to tones in noise. First, temporal reliability, a measure of discharge time consistency across stimulus repetitions, decreased with increasing tone level for most AVCN neurons at all measured CFs. Second, synchronization to the tone frequency, a measure of phase-locking to the tone, increased with tone level for low-CF neurons. Third, rapid fluctuations in the poststimulus time histograms (PSTHs) decreased with tone level for a number of neurons at all CFs. For each of the three temporal measures, some neurons had detection thresholds at or below psychophysical thresholds. A physiological model of a higher-stage auditory neuron that received simple excitatory and inhibitory inputs from AVCN neurons was able to extract the PSTH fluctuation information in a form of decreased rate with tone level.

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.

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.

Here we show that mild hearing loss induced by noise exposure in early age causes a decrease in neural temporal resolution when measured in adulthood. We investigated the effect of this chronic hearing loss on the representation of a voice onset time (VOT) and a gap-duration continuum in primary auditory cortex (AI) in cats, which were exposed at the age of 6 weeks to a 120-dB SPL, 5-kHz 1/3 octave noise band for 2 h. The resulting hearing loss measured using auditory brainstem responses and cortical multiunit thresholds at 4-6 months of age was 20-40 dB between 1 and 32 kHz. Multiple single-unit activity was recorded in seven noise-exposed cats and nine control cats related to the presentation of a/ba/-/pa/ continuum in which VOT was varied in 5-ms step from 0 to 70 ms. We also obtained data for noise bursts with gaps, of duration equal to the VOT, embedded in noise 5 ms after the onset. Both stimuli were presented at 65 dB SPL. Minimum VOT and early-gap duration were defined as the lowest value in which an on-response, significantly above the spontaneous activity, to both the leading and trailing noise bursts or vowel was obtained. The mild chronic noise-induced hearing loss increased the minimum detectable VOT and gap duration by 10 ms. We also analyzed the maximum firing rate (FRmax) and the latency of the responses as a function of VOT and gap duration and found a significant reduction in the FRmax to the trailing noise burst for gap durations above 50 ms. This suggests that mild hearing loss acquired in early age may affect cortical temporal processing in adulthood.

Binaural neurons show remarkable sensitivity to temporal differences in the waveforms at the two ears. This ability obviously requires temporal coding of sound waveforms in the monaural afferents that converge on such binaural neurons. We introduce a new analysis to investigate how well responses of single monaural neurons support discrimination of decorrelations in waveforms. Spike trains from auditory nerve (AN) and anteroventral cochlear nucleus (AVCN) neurons of cats to many repetitions of a set of broadband and narrowband noise tokens were obtained. The normalized correlation between the noise tokens ranged from 0.99 to –1. A coincidence and signal detection analysis was used to perform a correlation discrimination task using the monaural spike trains. The correlation discrimination thresholds derived from AVCN neurons were lower than those derived from AN fibers and sometimes as low as human psychophysical just noticeable differences. Importantly, low detection thresholds required comparisons of spike trains at small internal delays. Bandwidth dependence of neural decorrelation thresholds agreed with psychophysical data when large internal delays contributed to the detection. We conclude that, in the context of correlation discrimination, coding by AVCN fibers is superior to that by AN fibers and that these discriminations require a distribution of internal or best delays in binaural processing that differs from the predictions from studies of discrimination in interaural time delays.

To perform the jamming avoidance response (JAR), the weakly electric fish Gymnarchus detects time disparities on the order of microseconds between electrosensory signals received by electroreceptors in different parts of the body surface. This paper describes time-disparity thresholds of output neurons of the electrosensory lateral line lobe (ELL), where the representation of timing information is converted from a time code to a firing-rate code. We recorded extracellular single-unit responses from pyramidal cells in the ELL to sinusoidally modulated time disparity with various depths (0-200 μs). Threshold sensitivity to time disparities measured in 123 units ranged from 0.5 to 100 μs and was ≤5 μs in 60% of the units. The units from pyramidal cells in the inner and outer cell layers of the ELL responded equally well to small time disparities. The neuronal thresholds to time disparities found in the ELL are comparable with those demonstrated in behavioral performance of the JAR. The sensitivity of ELL units to small time disparities was unaffected when the center of the cyclic time-disparity modulation was shifted over a wide range (up to 250 μs), indicating an adaptation mechanism for steady-state time disparities that preserves the sensitivity to small dynamic changes in time disparities. Phase-locked input neurons, which provide time information to the ELL by phase-locked firing of action potentials, did not adapt to steady-state time shifts of sensory signals. This suggests that the adaptation emerges within the ELL.