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Laboratory of Sensory Neuroscience, Department of Psychology, Carleton University, Ottawa, Ontario, Canada
Submitted 5 May 2006; accepted in final form 19 August 2006
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Joris et al. 2004; Langner 1992). Differences in the response to AM sounds at different levels of the auditory system suggest a progressive modification of the neural code for temporal features. Neurons in the eighth nerve or the cochlear nucleus show synchronous responding to the envelope of AM tones at higher modulation rates than neurons in the inferior colliculus (ICC) or auditory cortex. Also, many neurons in the ICC and other central auditory structures show selective firing to specific bands of modulation frequencies, whereas those in the eighth nerve do not typically show selective firing to specific modulation rates (Joris and Yin 1992; Langner and Schreiner 1988; Schreiner and Langner 1988). The physiological data suggest the emergence of a place code for modulation frequency at higher levels of the central auditory system (Frisina 2001; Joris et al. 2004).
In the rat, responses to sinusoidal AM tones have been recorded in the cochlear nucleus (Møller 1974), the superior paraolivary nucleus (Kulesza et al. 2003), the inferior colliculus (Møller and Rees 1986; Palombi et al. 2001; Zhang and Kelly 2003), and the auditory cortex (Gaese and Ostwald 1995; Kilgard and Merzenich 1999), but so far there are no published reports on the responses of the neurons in the rat's lateral lemniscus. Data from the ventral nucleus of the lateral lemniscus (VNLL) are of particular interest because previous results suggested that this structure is important for processing temporal acoustic information (Batra and Fitzpatrick 1999; Covey and Casseday 1991; Zhang and Kelly 2006). Furthermore, this nucleus is a major source of inhibition that likely shapes emergent temporal responses of neurons in the auditory midbrain, e.g., the central nucleus of the ICC and/or higher auditory structures (Oertel and Wickesberg 2002).
Responses to sinusoidal AM tones have been studied in detail with respect to the bat's VNLL, which is an anatomically complex structure consisting of two distinct subdivisions: a columnar area and a multipolar area (Huffman et al. 1998). Neurons in the columnar subdivision respond poorly or not at all to AM tones, whereas those in the multipolar subdivision respond with a high degree of synchrony to the modulation cycle of sinusoidal AM tones. The results from the big brown bat, however, cannot readily be generalized to other mammalian species including the rat, whose VNLL is relatively undifferentiated and not segregated into separate populations of cells (Malmierca and Merchán 2004; Mechán and Berbel 1996; Zhao and Wu 2001). So far, there has been only one report of responses to AM tones in the VNLL of a relatively nonspecialized mammal, the rabbit (Batra 2006).
The purpose of the present study was to examine responses of neurons in the rat's VNLL to sinusoidal AM tones. The results provide data that are important for understanding how information about the temporal structure of sounds is represented at the level of the lateral lemniscus.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Experiments were conducted on 26 male adult Wistar albino rats (Rattus norvegicus) (250–500 g) obtained from Charles River Canada (St. Constant, Quebec, Canada). The animals were 10–18 wk of age at the time of the experiments. The external ears and tympanic membranes of all animals were examined with an otoscope and determined to be free of infection or other abnormalities. Animals were anesthetized with an initial injection of a combination of ketamine hydrochloride [60 mg/kg, administered intramuscularly (im)] and xylazine hydrochloride (10 mg/kg, im) and supplemental injections of ketamine hydrochloride (20 mg/kg, im) and xylazine hydrochloride (3.3 mg/kg, im) at intervals of about 45 min throughout the course of an experiment.
A midline incision was made in the scalp and the skin and muscles were retracted laterally. A small craniotomy was made to permit insertion of a pipette for recording responses from the VNLL. Several small screws were placed in the skull dorsally and fixed to a stainless steel rod with dental acrylic. The rod was then attached to a stereotaxic instrument and the head was held firmly in place, leaving the external ear canals free for insertion of earphone drivers. Recordings were made with the rats inside a single-wall sound-attenuated booth (Eckel Industries)
All procedures used in these experiments were approved by the Carleton University Animal Care Committee and were in accordance with the guidelines of the Canadian Council on Animal Care.
Sound stimulation
Sounds were presented monaurally to the right ear through a sealed headphone assembly (Beyerdynamic DT 48) connected to a hollow speculum (3 mm in diameter at the tip) that was fit against the rat's external meatus. To reduce acoustic cross talk, a second headphone assembly was fit into the left external ear, although no sound was delivered through the headphone. The acoustic waveforms were generated digitally by MALab 881 software controlled by a Macintosh G-3 computer. The sound-generation and data acquisition system (MALab 881) was designed and developed by Dr. Malcolm Semple (Center for Neural Science, New York University) and Steve Kaiser (University of California, Irvine) and produced by Kaiser Instruments.
The stimuli used in this study included noise bursts, tone bursts, and sinusoidal amplitude-modulated (AM) tones. Noise bursts (100-ms duration, 10-ms rise–fall time) served as a search stimulus. Tone bursts (100-ms duration, 10-ms rise–fall time) were used to determine each single neuron's characteristic frequency (CF, the frequency at which the neuron showed the lowest threshold for generating action potentials) and its temporal firing pattern. To examine the temporal firing pattern, a tone burst was presented 20 times to generate a summed peristimulus time histogram (PSTH). AM tones (10-s duration, 10-ms rise–fall time) were used to study how modulation rate, modulation depth, and stimulus intensity were reflected in the strength of firing and the degree of synchronization of spike discharges. An AM tone was presented twice at a rate of one presentation every12 s to generate a summed response.
The sound pressure level (SPL) for all stimuli was calibrated over a frequency range of 100–40,000 Hz using a condenser microphone (Brüel & Kjær 4134) inserted into one port of a small chamber constructed from Tygon tubing to mimic the volume of the rat's external ear. The tip of the hollow speculum was inserted into the other port of the chamber to form a tightly sealed enclosure for making pressure measurements. The acoustic response of the headphone assembly was adjusted on-line to provide a constant SPL over the range from 500 Hz to 30 kHz.
Recording electrode and recording procedure
A single-barrel glass pipette was used for extracellular recordings of responses from single neurons in the VNLL. The electrode had a tip about 2 µm in diameter and was filled with 3 M potassium chloride or 1.5% biocytin in 0.5 M potassium chloride solution. The impedance of the electrodes was typically about 10 M
. The electrodes were driven by a Kopf model 650 micropositioner. Neural activity registered by the electrode was amplified by a Dagan EX 4–400 Quad differential amplifier and digitized and discriminated on the basis of amplitude and waveform using an A/D converter and MALab 881 software. The occurrence times of spikes were recorded with a 1-µs resolution, stored on a computer, and processed later with standard database and graphics software.
During a recording session, the left VNLL was approached obliquely with the electrode in the coronal plane and tilted by 30° relative to the sagittal plane. Stereotaxic coordinates were referenced to a point 6.2–6.7 mm lateral and 0.5–0.9 mm rostral to the lambda. The electrode was lowered into the brain to a depth between 6.2 and 8.8 mm while searching for responses to acoustic stimulation.
The recording locations in VNLL, as determined by our stereotaxic coordinates, were verified by iontophoretic release of biocytin hydrochloride through the recording pipette in eight of the 26 animals. Biocytin was released by applying a train of 1-µA positive current pulses (7-s duration and 7-s interpulse interval) to the recording pipette following the procedures described in Zhang and Kelly (2006). The biocytin deposit was visualized by reaction of histological sections with the avidin–biotin complex in a Vectastain ABC kit (Vector Laboratories, Burlingame, CA). In each case the biocytin deposit was located within the cytoarchitectonic boundaries of VNLL. The dorsoventral location of the recording site was determined for each neuron from the depth of the electrode penetration within the brain, as shown in Fig. 11.
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Data analysis
The firing patterns for responses to tone bursts and sinusoidal AM tones were determined from all neurons involved in this study. Based on shapes of the PSTHs, responses to tone bursts were categorized into two broad groups: onset and sustained. Onset responses were defined as those with a single action potential or a transient burst of action potentials at the beginning of a tone burst followed by inactivity for the remainder of the sound (100 ms). Sustained responses were defined as those with sound-evoked activity for the duration of the tone burst. These included responses with a prominent transient discharge followed by a sustained level of firing (i.e., a primary-like pattern) as well as those with other types of temporal characteristics (for details, see Zhang and Kelly 2006).
For a response to an AM tone, we examined the average firing rate over the duration of the sound and the extent to which spikes were synchronized with the modulation envelope. Spikes recorded during the first 100 ms of each stimulus presentation were excluded from the analysis to avoid contamination by transient onset activity.
Period histograms were constructed to show the summed distribution of spikes over a modulation cycle and the degree to which spike discharges were synchronized with the modulation envelope. A measure of vector strength, as described by Goldberg and Brown (1969), was used to quantify the synchrony of neural firing with the modulation envelope of the AM stimulus. Vector strength (VS) was defined as follows
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i is the phase of spike i relative to the sinusoidal modulation cycle [i.e., 2
(modulation frequency) x (occurrence time of spike i)]. Perfect phase-locking (i.e., all spikes occurred at a single phase angle) results in a VS of 1.0, whereas a complete lack of synchronization between the neural firing and the modulation waveform results in a VS of 0. The Raleigh statistic was used to determine whether there was a statistically significant degree of synchrony in the firing to the modulation cycle of an AM tone (Batschelet 1981). Data points that fall below a significant level of synchrony (P < 0.001) are indicated in the captions of relevant figures. The effect of modulation rate was examined by recording the firing rates and the vector strengths over a wide range of modulation frequencies and plotting a firing rate modulation transfer function (MTFFR) and a vector strength modulation transfer function (MTFVS). To generate both the MTFFR and the MTFVS, the carrier frequency of the AM tone was set at the neuron's CF, the intensity of the sound was adjusted to 10 dB above threshold at CF, and the depth of AM was fixed at 100%. For some neurons we compared the MTFFR's and MTFVS's obtained at various intensities with those obtained at 10 dB above threshold at a neuron's CF to determine how the stimulus intensity affected responses to AM tones. We also examined firing rates and vector strengths obtained at various modulation depths. To study the effect of modulation depth, the modulation frequency was fixed, typically at the best modulation frequency as determined from the MTFFR, with the SPL at 10 dB above the cell's threshold at CF.
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RESULTS |
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Frequency of AM
For most neurons the firing rate and vector strength were highly dependent on modulation frequency, as illustrated by the example in Fig. 1. This neuron had a sustained firing pattern in response to tone bursts (Fig. 1A) and responded to AM tones at all modulation frequencies between 1 and 1,000 Hz (Fig. 1, B and C). The neuron generated its maximum number of spikes when the modulation frequency was 200 Hz. At this frequency, spikes were clustered around a specific phase of the modulation cycle (Fig. 1C). The number of spikes was reduced and the spike temporal distribution was widened at both higher and low modulation frequencies. At modulation frequencies between 700 and 1,000 Hz, spikes were almost evenly distributed over the modulation cycle. Both MTFFR and MTFVS peaked at 200 Hz (Fig. 1, D and E).
Figure 2A shows responses to AM tones for a neuron with onset firing to tone bursts. This neuron generated highly synchronous firing when the modulation frequency was between 40 and 300 Hz, and the firing rate peaked at 100 Hz (Fig. 2, B and C). The MTFFR had a band-pass shape with a narrow bandwidth (Fig. 2D) and the vector strength was high at all modulation frequencies between 40 and 300 Hz (Fig. 2E). This pattern of responding was typical of neurons with onset response to tone bursts.
Modulation frequency and firing rate
The majority of VNLL neurons displayed a band-pass MTFFR in response to sinusoidal AM tones, where band-pass was defined as a single peak of activity with 
30% reduction in firing rate on both high- and low-frequency sides of the peak (Figs. 1, 2, and 3A). Some neurons, however, showed other types of MTFFR as indicated in Fig. 3, B–E. These included high-pass and low-pass (defined by an asymmetrical reduction in firing of 30%), band-suppressed/bimodal (30% reduction compared with firing at high- and low-frequency peaks), and all-pass (<30% reduction in firing at any frequency). Out of the 41 neurons with sustained firing to tone bursts, 22 had band-pass, four had all-pass, five had high-pass, five had low-pass, and five had band-suppressed/bimodal MTFFR's. Out of the 25 neurons with onset responses to tone bursts, 23 had band-pass and two had bimodal MTFFR's. Thus for our entire sample of 66 VNLL neurons, 68% had band-pass MTFFR's. The average maximum firing rate produced by AM tones was similar for onset and sustained neurons. There was no statistically significant difference between the means for these two groups.
Onset neurons, in general, were more narrowly tuned than sustained neurons to modulation rate, as shown in Fig. 4. The bandwidth of the MTFFR as determined by a 30% reduction in activity relative to maximum firing rate tended to be narrower for onset cells than for sustained cells. The means were 90 and 280 Hz, respectively. The distribution of bandwidth was statistically different for these two groups of cells (Kolmogorov–Smirnov test, P < 0.05).
For each of the neurons that had a band-pass MTFFR, we determined the best modulation frequency (i.e., the modulation frequency at which the strongest firing was elicited) and the 50% cutoff point at the upper end of the MTFFR. The best modulation frequencies were widely distributed over the range between 10 and 500 Hz for neurons with sustained firing to tone bursts and between 10 and 300 Hz for neurons with onset firing (top panels of Fig. 5). The 50% cutoff points at the high-frequency flank of the MTFFR were also broadly distributed. The distributions were similar for neurons with sustained or onset responses to a tone burst (bottom panels of Fig. 5). In both groups of neurons, the lowest 50% cutoff point was 20 Hz. For six neurons with sustained responses and three neurons with onset responses, the 50% cutoff points were >1,000 Hz.
Modulation frequency and vector strength
Three examples of MTFVS's are given in Fig. 6 along with their corresponding MTFFR's showing the relation between the two different measures of response to AM tones. For all neurons the vector strength dropped off at high modulation rates. In some cases the upper limit of synchronous responding was determined by a lack of response at high frequencies (Fig. 6B). In other cases, the vector strength dropped precipitously at high frequencies even though the neuron continued to fire (Fig. 6A), or stayed at high levels even though there was a substantial reduction in firing rate (Fig. 6C). Thus the shapes of the MTFVS and the MTFFR were different in many cases. As can be seen in Fig. 6 the best modulation frequency for vector strength (the frequency that produced the highest vector strength) was often, but not always, the same as that for firing rate.
For each of the 66 neurons that fired continuously to AM tones, we examined the maximum degree of synchronization to the modulation cycle (Fig. 7). Neurons with sustained responses to tone bursts had peak vector strengths at modulation frequencies between 10 and 350 Hz (except for one neuron with a maximum vector strength at 1 Hz). For this group of neurons, the maximum vector strengths ranged from 0.37 to 0.98 with a mean of 0.79 and a median of 0.84. For neurons with onset responses, the best modulation frequencies covered the range from 10 to 400 Hz. Maximum vector strengths ranged from 0.78 to 0.99 with a mean of 0.93 and a median of 0.94. The maximum vector strengths for neurons with onset responses were statistically different from those with sustained responses (Kolmogorov–Smirnov test, P < 0.001).
We examined the relation between the vector strength of responses to AM tones and the jitter (SD) in first spike latencies of responses to tone bursts (Fig. 8). Neurons with onset responses had very high maximum vector strengths and very little jitter in first spike latency. For these neurons, the SDs of the first spike latencies ranged between 0.053 and 3.1 ms for responses to tone bursts at 20 dB above threshold at CF. There was a significant negative correlation between vector strength and jitter for these cells (r = –0.48, df = 19, P < 0.05). For neurons with sustained responses to tone bursts, on the other hand, both vector strength and jitter in first spike latency were more broadly distributed. The SDs in first spike latency for these neurons ranged from 0.14 to 17.2 ms; the correlation between vector strength and degree of jitter was marginally significant (r = –0.26, df = 42, P < 0.05).
Modulation depth
In 27 VNLL neurons, we examined the effect of changing modulation depth on responses to AM tones. For this purpose, the carrier frequency was set at the neuron's CF and the modulation frequency was fixed at a value that produced maximum firing at 100% modulation depth as determined from the neuron's MTRFR. Twenty of these neurons showed sustained responses and seven showed onset responses to tone bursts. For 19 of the 27 neurons, including 12 with sustained and seven with onset firing, an increase in modulation depth resulted in a monotonic increase in firing rate. For the remaining eight neurons, all with a sustained firing pattern, an increase in modulation depth resulted in a nonmonotonic change in firing rate. For the entire population of 27 cells the firing rate was reduced by 42% as the modulation depth was lowered from 100 to 10%. The average curves for all neurons, monotonic and nonmonotonic neurons, are shown separately in the three left-hand panels of Fig. 9. The corresponding vector strength curves for these same groups of neurons are shown in the right-hand panels of Fig. 9.
Neurons with nonmonotonic firing rate curves did not always have nonmonotonic vector strength curves. An increase in modulation depth resulted in a monotonic increase in vector strength in 20 neurons. The remaining seven neurons displayed nonmonotonic changes. For the entire population of 27 neurons, the mean vector strength was reduced from 0.81 to 0.33 as the modulation depth was lowered from 100 to 10%, as indicated in the top right-hand panel of Fig. 9.
Stimulus intensity
We examined the effects of stimulus intensity on modulation transfer functions in 31 neurons. For 25 of the 31 neurons, including 12 with sustained and 13 with onset firing, an increase in intensity from 10 dB above threshold at CF to higher values altered the MTFFR as indicated in Fig. 10 (left panels). For most neurons there was either an increase (total = 13; seven sustained and six onset) or a decrease (total = 4; one sustained and three onset) in firing that occurred generally over a wide range of modulation frequencies and was proportional to the firing rate at 10 dB (Fig. 10, A and B). For other neurons the change in firing rate was frequency dependent and not proportional to the firing rate at 10 dB above threshold (total = 8; four sustained and four onset). For these neurons the shape of the MTFFR was altered by an increase in stimulus intensity (see, for example, Fig. 10C). For the remaining six neurons (five sustained and one onset), there was no change in firing rate at any frequency as a result of the increase in stimulus intensity (not shown).
Of the 25 neurons whose firing rate was altered by an increase in stimulus intensity, only 11 (seven sustained and four onset) showed any substantial change in vector strength. Two neurons (both onset) showed an increase, seven (five sustained and two onset) showed a decrease (Fig. 10C) and two (both sustained) showed either an increase or a decrease in vector strength depending on the modulation rate (Fig. 10A). For 14 neurons (five sustained and nine onset) there was no change in vector strength despite substantial alterations in the MTFFR (Fig. 10B). There was also no change in vector strength for the additional 6 neurons that showed no change in firing rate.
Correlation with depth of recording locus
The relation between the best modulation frequency based on the MTFFR and position along the dorsoventral length of VNLL is shown in Fig. 11A. Sustained and onset neurons are indicated by filled and unfilled circles, respectively. The best modulation frequencies were widely distributed along the full extent of VNLL. The correlation between the best modulation frequency and location in VNLL was not statistically significant (r = –0.09; P > 0.05), nor was there any significant correlation between location and best modulation frequency as defined by the MTFVS (r = –0.10; P > 0.05) (Fig. 11B). Furthermore, there was no significant correlation between location and maximum vector strength (r = –0.15; P > 0.05) as shown in Fig. 11C. Also, there was no obvious relation between any of these temporal response measures and dorsal to ventral position when neurons with onset or sustained responses were considered separately.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Many neurons in the rat's VNLL produced action potentials that were highly synchronized to the modulation envelope of AM tones. At their best modulation frequencies neurons with onset responses to tone bursts showed particularly high levels of response synchrony to AM tones with maximum vector strengths that were rarely <0.8. They also showed very low levels of jitter in their first spike latencies to tone bursts. Among cells with onset responses there was a significant correlation between vector strength and jitter (r = –0.48). Many neurons with sustained responses to tone bursts also had high levels of synchronous discharge to AM tones, but the distribution of values was broader with maximum vector strengths that ranged from 0.4 to 0.98. Many of the sustained neurons in VNLL had low levels of jitter in their first spike latency, but the correlation between vector strength and jitter (r = –0.26) was not as strong as that found with onset neurons. In general, the results are consistent with previous reports that neurons in the VNLL show high levels of temporal precision in their response (Batra and Fitzpatrick 1999; Covey and Casseday 1986, 1991; Zhang and Kelly 2006) and support the idea that the VNLL plays an important role in processing temporal information in the central auditory system (Oertel and Wickesberg 2002).
The responses of VNLL neurons to AM tones were previously examined in rabbits and big brown bats (Batra 2006; Huffman et al. 1998). In the rabbit, many neurons within VNLL show high levels of response synchrony similar to that found in the rat. Neurons with onset responses to tone bursts have higher levels of response synchrony to AM tones (maximum vector strengths) than those with sustained responses to tone bursts (Batra 2006). Furthermore, neurons with high levels of synchrony to AM tones are found throughout the VNLL, which is relatively undifferentiated anatomically and similar in appearance to that in the rat (Malmierca and Merchán 2004; Merchán and Berbel 1996).
In contrast, the responses to AM tones in the VNLL of the big brown bat are dependent on the anatomical subdivision from which recordings are made. The VNLL in the big brown bat consists of a multipolar area, which contains primarily neurons with radial dendrites, and a columnar area, which contains small round neurons tightly packed into a distinctive columnar configuration (Covey and Casseday 1995). Within the multipolar region many of the neurons with either sustained or onset responses to tone bursts exhibit high levels of synchrony to the envelope of AM tones (Huffman et al. 1998). On the other hand, neurons in the columnar region typically have very precisely timed onset responses to tone bursts, but show little or no synchronized response to AM tones. These neurons usually respond only at the onset of an AM stimulus, but do not respond to the recurring cycles of modulation.
The modulation rates that produce maximum vector strengths for AM tones in the rat's VNLL cover a wide range from 10 to 400 Hz, with roughly the same distribution for onset and sustained cells. Neither of these populations, however, has cells with synchronized responses at AM rates as high as those found in eighth nerve neurons, which typically show synchronized responses 
1 kHz (Frisina 2001; Joris and Yin 1992; Joris et al. 2004). The absence of a synchronized response at high modulation rates in VNLL neurons is, in many cases, related to a reduction in the level of firing at these rates. In some cases, however, a drop-off in vector strength is apparent even when firing rates remain quite high. The wide distribution of modulation rates to which VNLL neurons are sensitive is comparable to that found in the cochlear nucleus (Backoff et al. 1999; Frisina et al. 1990a,b; Kim et al. 1990; Møller 1972, 1974, 1976; Rhode and Greenberg 1994; Zhao and Liang 1995, 1997). In both cochlear nucleus and VNLL, however, the maximum vector strengths produced at preferred modulation frequencies are often substantially greater than those recorded from eighth nerve neurons. Similar results regarding the limits of synchronized responding to AM tones have been reported for VNLL neurons in both rabbits (Batra 2006) and big brown bats (Huffman 1998).
In general, the neurons in the rat's VNLL show synchronized responses at AM rates well above those that produce synchrony in the ICC under the same experimental conditions (Zhang and Kelly 2003). In the rat's ICC the best modulation frequencies as determined from the MTFVS ranged from 10 to 100 Hz compared with a range of 10–400 Hz in VNLL. Responses to AM tones (or repetitive pulses) are even more limited in the rat's auditory cortex, where the vast majority of neurons show peak response synchrony to rates <12–15 Hz (Gaese and Ostwald 1995; Kilgard and Merzenich 1999).
Effects of amplitude modulation on firing rate
The neurons in the rat's VNLL had various shapes of MTFFR, with most neurons showing selectivity for a specific modulation frequency or frequencies. The most common type was the band-pass function, which was characterized by a single peak of maximum firing over a narrow range of modulation frequencies with reduced firing at both higher and lower frequencies. Similar results were previously reported for neurons located in the cochlear nucleus or other brain stem auditory nuclei (Backoff et al. 1999; Zhang and Kelly 2003). Among the VNLL neurons with band-pass MTFFR, the best modulation frequencies were widely distributed from 10 to 500 Hz for sustained cells and from 10 to 300 Hz for onset cells. Neurons with onset responses to tone bursts had band-pass functions that were generally more narrowly tuned to modulation rate than those with sustained responses, suggesting that they might play an important role in the neural processing of temporal properties of sounds. The band-pass tuning of neurons to specific modulation rates and the range of preferred rates in their MTFFR's suggest that modulation rate (or other temporal properties of sound) could be encoded in VNLL in terms of which neurons are activated rather than their temporal firing patterns. Different AM rates would be expected to activate different populations of neurons in VNLL, although the topographic distribution of activity is not presently known. Thus selective firing of VNLL neurons could contribute to the spatial representation of AM at higher levels of the auditory system as previously described for ICC and auditory cortex (Frisina 2001; Langner 1992; Langner and Schreiner 1988).
Many neurons in the rat's VNLL (32%) had MTFFR's that were not band-pass. These included neurons with band-suppressed, bimodal, high-pass, or low-pass MTFFR. The various types of MTFFR in VNLL were similar to those reported for ICC neurons in rats, gerbils, and other mammals (Krishna and Semple 2000; Zhang and Kelly 2003). As previously suggested by Krishna and Semple (2000) based on their studies of gerbil inferior colliculus, band-suppressed or bimodal MTFFR's reflect emergent response properties not found in more peripheral structures such as the ventral cochlear nucleus, which is the primary source of lower brain stem projections to the VNLL. Therefore bimodal, band-suppressed, and perhaps other types of response to AM tones likely emerge locally within the VNLL.
Excitatory/inhibitory interactions in VNLL
One contributing factor in shaping responses in the VNLL to time-varying auditory stimuli is likely the convergence of excitatory and inhibitory inputs from lower auditory structures. The VNLL receives direct excitatory projections from the contralateral VCN (Adams 1997; Cant 1992; Friauf and Ostwald 1988; Huffman and Covey 1995; Schofield and Cant 1997; Vater and Feng 1990; Zook and Casseday 1985). These projections originate from octopus cells and bushy cells, both of which have properties that preserve the timing of neural responses in the auditory pathway (Rhode et al. 1983; Smith et al. 1993a,b; Wu and Oertel 1984). In addition, the VNLL receives direct afferent inhibitory inputs from GABAergic and glycinergic neurons located in the medial, ventral, and lateral nuclei of the trapezoid body (van Adel 1998; Warr and Beck 1996). Neurons in the medial and ventral nuclei of the trapezoid body receive their excitatory input from the contralateral VCN and send their projections to the ipsilateral VNLL. Thus a sound presented to one ear would result in both excitatory and inhibitory postsynaptic effects on neurons located in the contralateral VNLL.
The prevalence of excitatory and inhibitory projections onto VNLL neurons was earlier confirmed by brain slice studies (Irfan et al. 2005; Wu 1999; Zhao and Wu 2001). Many neurons in the rat's VNLL receive both excitatory and inhibitory synaptic inputs from ascending fibers in the lateral lemniscus. Also, in vivo intracellular recordings by Nayagam et al. (2005) provide strong evidence of a local inhibitory feedback circuit within the rat's VNLL.
The interaction of excitatory and inhibitory projections could result in band-suppressed or bimodal MTFFR's in VNLL by producing a reduction in firing at some modulation rates and an increase in firing at other rates. Furthermore, some neurons in the rat's VNLL change the shape of their MTFFR with changes in stimulus intensity. For example, the modulation rates that produce a reduction in firing at one SPL can cause an increase in firing at other levels, as shown in Fig. 10C. These effects might be explained by the convergence of excitatory and inhibitory inputs onto VNLL neurons with the excitation or inhibition dependent on the SPL of the stimulus. A level-dependent combination of rate-specific excitatory and inhibitory effects could account for the complex MTFFR profiles found in VNLL.
The convergence of excitation and inhibition can affect the level of synchrony of responses in the auditory system. For example, it was previously shown that the synchrony of responses in the mustached bat's medial superior olive was enhanced by the presence of an inhibitory input and reduced by local application of the glycine receptor antagonist strychnine (Grothe 1994; Grothe et al. 1997). Thus it is possible that the high level of synchronous responding to AM tones among neurons in the rat's VNLL is explained in part by local inhibitory synapses. Further studies with neurotransmitter receptor antagonists are needed to determine how excitatory and inhibitory inputs to VNLL affect response to modulated tones.
Topography of VNLL responses to AM tones
Langner et al. (2003, 2006) suggested that the rate of AM of an auditory stimulus might be represented topographically along the dorsal–ventral axis of VNLL. According to this idea, the dorsoventral location of a neuron in VNLL should be correlated with the best modulation frequency regardless of the carrier frequency of a modulated tone. The results of the present study, however, do not provide support for this hypothesis. In the rat's VNLL there is no significant correlation between a neuron's best modulation frequency as determined from its MTFFR and its dorsoventral location within VNLL. There was also no significant correlation between dorsoventral position and maximum vector strength or the preferred modulation frequency determined from the MTFVS. These results do not rule out the possibility that there is some other form of spatial code for modulation rate, but they reduce the likelihood of a dorsoventrally oriented topography.
In conclusion, we found that the neurons in rat's VNLL were very sensitive to modulations in the amplitude of tones, suggesting that these cells might play a role in the perception of temporal structure of complex sounds. The responses of the neurons, particularly those with onset responses to tone bursts, were well synchronized to the envelope of AM tones with an upper frequency limit substantially higher than that seen in IC, but lower than that in peripheral structures such as the 8th nerve or cochlear nucleus. Also, the firing rates of VNLL neurons were clearly dependent on the frequency of AM tones and the best modulation frequencies for neurons with band-pass MTFFR covered a wide range, suggesting that the AM rate could be represented in terms of which VNLL neurons are activated. Neurons with onset responses to a tone burst had generally narrower tuning to modulation rate than those with sustained responses. However, there was no indication of a topographic representation of AM rate along the dorsoventral axis of VNLL for either onset or sustained neurons.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: J. B. Kelly, Department of Psychology, Carleton University, 329 Life Science Research Building, Ottawa, Ontario, Canada K1S 5B6 (E-mail: jkelly{at}ccs.carleton.ca)
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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