single unit responses in the inferior colliculus of the awake and performing rhesus monkey

Exp. Brain Res. 32, 389-407 (1978) Experimental

Brain Research

@ Springer-Verlag 1978

Single Unit Responses in the Inferior Colliculus of the Awake and Performing Rhesus Monkey*

A. Ryan 1 and J. Miller

Regional Primate Research Center, and Departments of Physiology & Biophysics and Otolaryngology, University of Washington, Seattle, Washington 98195, U.S.A.

Summary. 1. The activity of single units in the inferior colliculus of unanesthetized monkeys was recorded during performance in an auditory reaction time task. Stimulus intensity and frequency were varied.

2. Spontaneous rate of unit discharge varied from 0 to 78.2 discharges per second, with a mean of 14.7 discharges/sec.

3. Both broadly and narrowly tuned units were encountered in the central nucleus of the inferior colliculus. The temporal discharge pattern of most units varied with changes in stimulus frequency; onset bursts and/or sustained discharge suppression dominated the unit discharge at the edges of receptive fields.

4. Hal f of the units examined at several intensity levels displayed nonmonotonic relationships between evoked discharge rate and stimulus intensity, with most nonmonotonic units showing a distinct "best intensity". The temporal response pat tern of almost all units varied with changes in stimulus intensity, with onset bursts and discharge suppression increasing in occurrence with increasing intensity.

5. Units recorded in the external nucleus of the inferior colliculus displayed spontaneous rates which were similar to those of central nucleus units, and were affected by variation in stimulus intensity in the same fashion. However, the average initial latency of such units to intense stimuli was longer than the latency of central nucleus units.

6. Variations in unit discharge with changes in stimulus frequency and intensity are consistent with an interaction of excitatory and inhibitory inputs with different initial latenc!es, dynamic ranges and receptive fields. In

* Based in part on a dissertation submitted to fulfill requirements for the degree of Doctor of Philosophy at the University of Washington. Supported by grants NS08181, RR00166 and GM 00666 from the National Institutes of Health, U.S. Public Health Service 1 Present address: Division of Otolaryngology, Department of Surgery, University of California at San Diego School of Medicine, San Diego, California 92103, U.S.A. Offprint requests to: Allen Ryan, Ph. D. (address see above)

0014-4819 /78 /0032 /0389 /$ 3.80

390 A. Ryan and J. Miller

particular, our data suggest that inhibitory inputs have longer initial latencies and higher thresholds. Inhibition is stronger at the edges of a unit's receptive field, and dominates at high frequencies in units with low characteristic frequency.

7. Our data are not consistent with previous reports that single units in the unanesthetized animal display uniformly monotonic intensity functions and uniformly broad frequency responses.

Key words: Inferior colliculus - Single units - Unanesthetized monkey - Response plasticity

Several investigations of the response characteristics of single units in the inferior colliculus (IC) of the anesthetized animal have established that neurons at this level of the auditory system may exhibit quite narrow tuning across frequency, as well as markedly nonmonotonic relationships between evoked discharge rate and stimulus intensity (Rose et al., 1963; Erulkar, 1959; Hind et al., 1963). From an examination of published figures, it is apparent that IC units in anesthetized animals discharge spontaneously at very low rates (Rose et al., 1963). Several recent studies have also demonstrated that the response patterns of IC units can vary widely with changes in stimulus parameters such as frequency, intensity, interaural phase or interaural intensity (Rose et al., 1963; Geisler et al., 1969; Stillman, 1971; Pollack et al., 1977).

Techniques for single unit recording in the alert animal have been extensively used for the examination of discharge characteristics in auditory cortex. These techniques have been used to assess the effects of anesthesia and state of arousal (Pfingst et al., 1977), behavioral training (Woody et al., 1976) and performance (Miller et al., 1972; Beaton and Miller, 1975) upon single units at the cortical level. In such studies it has been demonstrated that anesthetics can significantly depress the responsiveness of cortical neurons (Pfingst et al., 1977). Alternatively, both classical and operant conditioning with auditory stimuli appear to increase neural responsiveness (Miller et al., 1972; Woody et al., 1976). These findings indicate that data recorded from the cortex of anesthetized preparations may be extrapolated to the awake and behaving animal only with caution.

Recently, chronic recording techniques have been applied to the study of IC single units. Bock et al. (1972) reported that IC single units in the unanesthetized cat showed response characteristics which were quite different from those seen in anesthetized animals. In particular, they found that IC units recorded from the unmedicated preparation displayed high spontaneous rates of discharge, broad frequency responses and uniformly monotonic relationships between evoked discharge rate and stimulus intensity. Bock et al. (1972) attributed these differences to anesthetic depression of certain aspects of IC unit activity. In particular, they felt that the effects of a general, anesthetic-related depression of neural excitability would be more apparent in discharge characteristics which are determined by a relatively limited number of synaptic events. Thus, spontaneous rate of discharge and the edges of receptive fields

IC Unit Responses in the Unanesthetized Monkey 391

would be selectively depressed by anesthesia. They also hypothes ized that

anesthet ics alter the na tu re of inhib i tory inputs to cells in the IC, by an unspecif ied mechanism, based on the lack of n o n m o n o t o n i c in tens i ty funct ions seen in their unanes the t i zed uni t sample. These f indings have p ro found implicat ions for the general i ty of data collected f rom anes thet ized preparat ions .

The present invest igat ion was u n d e r t a k e n to ex tend our knowledge of IC c e l l activity in the unanes the t i zed prepara t ion , and to evaluate the effects of ongoing behaviora l pe r fo rmance upon IC uni t activity. The behaviora l results have b e e n publ i shed elsewhere (Ryan and Miller, 1977). In this paper, paramet r ic f requency and in tens i ty data are presented . The observed changes in response pa t te rn in the unanes the t i zed m o n k e y are compared to observa t ions made in the awake and the anesthet ized cat prepara t ions . Obse rved differences are discussed in terms of anes the t ic - re la ted changes in input to IC cells. It should be no ted that data recorded dur ing task pe r fo rmance are no t always comparab le to those recorded wi thout per formance . In this repor t we have pooled data f rom these two behaviora l condi t ions when per fo rmance did no t appear to significantly affect the variable unde r considera t ion. Where pe r fo rmance has a s t rong effect upon a measure , the data are p resen ted separately. See Ryan and

Miller (1977) for a fur ther discussion of pe r fo rmance effects.

Methods

Subjects. Six young adult male rhesus monkeys (Macaca mulatta), weighing 2.5-3.4 kg, were used. Experimental sessions were conducted in a double-walled, sound-attenuating chamber (IAC 1200A). All behavioral and auditory control equipment was located outside the experimental chamber. Subjects were restrained in a standard primate chair during the experimental sessions, and were kept in cages at all other times. Sound Generation and Control White noise was generated by a General Radio Company Model 1381 random noise generator, with a bandwidth of 20 Hz to 50 kHz. Pure tones were generated by a Hewlett Packard Model 200 CR low-frequency oscillator. A Hewlen-Packard 350D attenuator pad permitted 0-110 dB attentuation of the signal in 1 dB steps. Stimuli were delivered through a TDH 49 ear speaker mounted in a rubber cuff which fitted over the external ear without pressing on the tragus and provided a closed acoustic system.

The stimulus delivery system was calibrated in small steps between 0.1 and 40 kHz. Signals were measured by a General Radio Company Model 1900 A wave analyzer, and a 1/2 inch Briiel and Kjaer condenser microphone with a calibrated probe tube which was inserted through a hole in the rubber cuff and terminated at the opening of the external auditory meatus. Further details of the sound presentation and delivery system have been described elsewhere (Pfingst et al., 1975). Behavioral Procedures. A detailed description of the procedures used in the training and testing of animals in the reaction-time task has been published previously (Stebbins and Miller, 1964). The animals were trained by successive approximations to final performance in a task which consisted of the following sequence: 1. following onset of a visual "alerting" stimulus, the subjects depressed a telegraph key; 2. the key was hqld down for a variable (1-4 sec) waiting period until the onset of a fixed duration 250 msec auditory stimulus, after which; 3. the animal released the key rapidly in order to obtain applesauce reinforcement. The reward was delivered only for key release with latencies of from 0.1 to 1.0 sec after stimulus onset; 4. following key release, a 2.0 sec stimulus-free period was imposed before onset of the next visual alerting stimulus. Premature (<0.1 sec after stimulus onset) or long latency responses (> 1.0 sec) initiated this stimulus-free, intertrial interval. The resulting delay in reinforcement was found to be sufficient to suppress inappropriate responses to an average level of less than 5 % of all bar presses. (It should be noted that stimuli near threshold intensity were rarely used in this investigation.)


In addition to training in the reaction time procedure, the animals were adapted to periods during which acoustic stimuli were presented repetitively in the absence of reinforcement. The monkeys quickly ceased to respond during these "nonperformance" intervals. In both the performance and nonperformance situations, white noise and a variety of pure tones were employed as stimuli. Surgical Procedures. Following stabilization of the animal's performance in the behavioral task, subjects underwent aseptic surgery. Each subject was given a pre-surgical dose of Vetalar ~, then intubated, anesthetized with Halothane vapor, and placed in a Kopf stereotaxic frame. A skin flap was reflected, and a circle of bone approximately 16 mm in diameter was removed. The location of the skin and bone removal was determined stereotaxically, and was appropriate for subsequent introduction of recording electrodes into the IC of the monkey. The stereotaxic coordinates for the IC in the sitting M. mulatta were taken from Smith et al. (1972). A stainless steel chamber (15 mm in height, 16 mm in outside and 13 mm in inside diameter) was implanted, also stereotaxically, over the surgical defect in the bone. In five animals the chamber was oriented in the coronal stereotaxic plane and directed toward the IC with a 17 ~ lateral angle. In one animal a direct vertical approach was employed. The end of the chamber was advanced to contact the dura lightly. The base of the chamber was threaded externally and internally and had an internal layer of silicon rubber which covered the threads and maintained a closed system in the chronic preparation. Dental acrylic was used to cement the chamber to the skull and to stainless steel screws threaded into the bone. A device that allowed rigid stabilization of the head during neurophysiological recording was also affixed to the skull. For further details regarding surgical procedures and stabilization, see Miller and Sutton (1976) and Pfingst et al. (1975). ElectrophysioIogical Recording. Behavioral sessions with head restraint were initiated after animals had fully recovered from surgery. Animals adapted easily to the restraint, and resumed normal behavior in the reaction time procedure within 1 4 days. At this point, neural recording was begun. A coupler was mounted on the implanted chamber which provided access to an area of 5 mm radius from the center of the chamber. A sterile 21 gauge needle cannula was attached to a Trent-Wells micromanipulator. A tungsten microelectrode, insulated with epoxylite and with an iron electroplated tip of 4 to 25 ~m diameter, was inserted into the cannula. The micromanipulator was inserted into the adjustable guide, which directed the cannula into the brain. With a cannula length of 54 mm, the needle terminated 6-10 mm above the IC. The electrode was then advanced out of the cannula with the hydraulic micromanipulator. White noise bursts with an intensity of 80-90 dB SPL, delivered in the nonperformance condition, were routinely used as a searching stimulus until the first evoked units were found on a given track. Single units were then tested with white noise and pure tones for the remainder of the track. Marking lesions were made on fruitful electrode penetrations, using a Grass Model LM54 DC constant current lesion-maker. Cathodal current of 40 uA was passed for 15-30 sec.

The signal from the microelectrode was initially amplified by a unity gain FET follower, and was further amplified by a Grass P511F preamplifier. The preamplifier output passed through a high pass (>0.5 kHz) filter and the filtered signal was monitored on a Tektronix RM565 oscilloscope and a Grass AM8 audio-monitor. The oscilloscope was internally triggered by the unit signals fed into the horizontal amplifier. Gate pulses from the oscilloscope were applied to the input of a dot raster system. The output pulses from the raster, along with the filtered electrode output and the acoustic stimulus, were displayed on a Tektronix 564 memory oscilloscope. The storage oscilloscope was triggered by onset pulses to the tone switch.

The output of the preamplifier was also recorded on one channel of a Honeywell Model 5600 FM tape recorder. Other channels recorded the onset and offset pulses from the tone switch, and the acoustic stimulus.

When a single unit was isolated, the discharge of which appeared to be affected by the acoustic stimulus, its response was examined with various frequencies and intensities under the performance condition. Since the number of stimulus presentations which could be obtained during performance was limited, it was not always possible to examine all appropriate stimuli under this condition. The animals often satiated before the end of an. electrode penetration, and in this event units were examined by presenting stimuli in the absence of performance. In this condition, stimuli were presented with a random interstimulus interval comparable to that of the performance condition. Data Analysis. All data were analyzed from the taped records of single unit activity. Units were isolated with the trigger of the RM 565 oscilloscope. Achievement of isolation was based upon the


2O

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z 5

0 [] []

0 ]0 20 30 40 50 60 70 80

SPONTANEOUS RATE (discherges/sec)

Fig. 1. Distribution of spontaneous rates observed in 128 IC single units

amplitude and slope of the spike waveform. If separation of the spike from other discharge activity on the trace could not be assured, all data from that unit were discarded. The internal trigger of the RM 565 oscilloscope was used as a Schmitt trigger for digitalizing the unit discharges. Statistical analysis of initial latencies and of firing rates for selected intervals, as well as the generation of PST histograms, was performmed by a Prime 200 computer. In some units with high spontaneous rates, measurement of initial latency was made from dot raster representations of the first 50 msec after stimulus onset. The majority of units encountered in the IC were excitatory and exhibited an inital phasic increase in discharge rate associated with stimulus onset, a sustained elevation in discharge throughout the stimulus, or both. Phasic responses lasted from 50-75 msec after stimulus onset. Therefore, two analysis intervals were selected to include a period from 0-75 msec after stimulus onset, and another from 75-200 msec after onset. These intervals permitted independent evaluation of the phasic and sustained components of unit responses. Spontaneous rate was measured in the 100 msec immediately preceding stimulus onset, for 100 stimulus presentations throughout the recorded data of each unit. Histology. After 8-12 days of neural recording, animals were deeply anesthetized with pentobarbitol (35 mg/kg) and perfused with saline solution followed by 10% formalin. The top of the skull was removed and the animal placed in a stereotaxic frame in the same position as that in which neural recording was performed. A knife blade was attached to an electrode carrier and used to cut a coronal section of tissue, which was parallel to the electrode tracks and contained all electrode penetrations. Frozen sections of 30 am were taken and alternate sections stained with cresyl violet. Identification of electrode tracks was made from these sections on the basis of the marking lesions.

Results

Histology. O n e h u n d r e d a n d t w e n t y - e i g h t I C u n i t s w e r e r e c o r d e d o n t a p e a n d

j u d g e d to b e s u i t a b l e f o r ana lys i s . O f t h e s e , 6 7 w e r e l o c a t e d in t h e c e n t r a l

n u c l e u s o f t h e IC, a n d 13 in t h e c a p s u l e o r e x t e r n a l n u c l e u s ( I C X ) o f t h e IC. T h e

p o s i t i o n o f t h e r e m a i n i n g 4 8 un i t s , w h i l e w i t h i n t h e IC, c o u l d n o t b e s p e c i f i e d as to e x a c t l o c a t i o n ( s ee R y a n a n d M i l l e r , 1 9 7 7 ) .

Spontaneous Discharge. S p o n t a n e o u s r a t e o f al l u n i t s w a s e v a l u a t e d . I t v a r i e d

f r o m 0 .0 to 7 8 . 2 d i s c h a r g e s / s e c , w i t h a m e a n v a l u e o f 14 .7 d i s c h a r g e s / s e c . T h e

d i s t r i b u t i o n o f o b s e r v e d s p o n t a n e o u s r a t e s f o r I C u n i t s is i l l u s t r a t e d in F i g u r e 1.


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Fig. 2. Average initial latency as a function of stimulus intensity for unit SR 17-4, recorded in the central nucleus of the IC. Each point represents 22 nonperformance presentations of an 0.8 kHz tone, the unit's CF. Vertical bars represent one standard deviation above and below each mean. The insert shows the relationship between stimulus intensity and discharge rate from 0-75 msec after stimulus onset, for the same stimuli. Stippling in this and all other figures represents the range of spontaneous rate observed for the unit throughout the recording period

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Fig. 3. a Average initial latency as a function of stimulus intensity for unit N 7-1, recorded in the central nucleus of the IC. Each point represents 21 presentations of white noise during reaction time performance. Vertical bars represent one standard deviation above and below each mean. b PST histograms for the same stimulus presentations

IC Unit Responses in the Unanes thet ized Monkey 395

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Fig, 4. a Distribution of average initial latencies to intense stimuli observed in 44 units with excitatory onset responses during behavioral performance, b distribution of average initial latencies to intense stimuli of 52 units observed while subjects sat passively during stimulus presentation. Several units for which performance data could not be obtained have been included. (Average nonperformance initial latency for the 44 units in Figure 4a was 15.23 msec, with a standard deviation of 7.45 msec)

Initial Latency. Initial latency was evaluated at various intensity levels in 38 units which displayed onset excitation in the absence of onset suppression. In all such units latency decreased exponentially with increasing intensity. This was the case both for units which displayed a monotonic and those showing a nonmonotonic relationship between evoked discharge rate and stimulus intensity (Fig, 2). A few units were encountered in which both excitation and suppression of dis_charge were evoked with short latency at stimulus onset. As one might expect, such units could display a varied relationship between initial

' latency and stimulus intensity. An example of this is illustrated in the post-stimulus time (PST) histograms and associated latency intensity function fo r the unit shown in Figure 3. At low stimulus intensities this unit 's response to white noise stimulation was a modest elevation in discharge between 50 and 150 msec after stimulus onset. With an increase in stimulus intensity a sustained suppression of discharge throughout the duration of the stimulus was superimposed upon this excitatory response. The net effect of this interplay of excitation and suppression upon initial latency was a relatively flat, highly variable latency-intensity function.

Because of the exponential nature of latency functions in units which displayed an excitatory onset response with no onset suppression, inital latencies to intense stimuli [90-110 dB SPL white noise or pure tone at characteristic frequency (CF)] could be compared across such units. Initial latencies to intense stimuli were recorded from 44 such units while the animal performed in the reaction time task. Average initial latencies ranged from 4.72 to 36.13 msec, with a mean of 17.10 msec (Fig. 4a). As was pointed out in a previous publication (Ryan and Miller, 1977), initial latency was consistently affected by reaction time performance. Initial latencies recorded during


Fig. 5. a CFs of single units observed on two penetrat ions of the IC near the center of the A - P extent of the nucleus, b similar data obtained in the posterior portion of the IC


performance were longer than those recorded from the same units without performance. Latencies of the units shown in Figure 4a, plus several additional units, were obtained in the nonperformance condition. The average initial latency of 52 units ranged from 4.50 to 35.57 msec, with a mean of 14.02 msec, when the subjects sat passively during the stimulus presentation (Fig. 4b). Effect of Stimulus Frequency. The tonotopic organization of the IC of the rhesus monkey was readily observed in our preparation. As illustrated in Figure 5a, when electrodes traveled from dorsal to ventral through the center of the central nucleus of the IC, CFs of units increased. If the electrode passed through the edge of the central nucleus of the IC, or through the lateral portion of the ICX, CFs tended to remain at about the same value. With more anterior electrode placements, higher CFs than those observed in posterior penetrations were seen. Units recorded from the posterior IC rarely displayed CFs above 2 kHz (Fig. 5b). While electrodes frequently passed through the dorsal portion of ICX,

which some authors have designated the pericentral nucleus (Berman, 1968; Geniac and Morest, 1971), so few units were isolated in this region that its organization could not be ascertained.

Forty-three units were examined at a variety of stimulus frequencies, by obtaining iso-intensity frequency functions at an intensity level 30-40 dB above each unit's threshold. Within this sample, three general categories of iso-intensity functions were observed. The functions of 17 units were "simple" elevations of discharge rate above spontaneous rate with a single, relatively narrow peak. Eleven units displayed "W" shaped functions, with a narrow excitatory region surrounded by frequency regions which elicited suppression of discharge to levels below spontaneous rate. Fifteen units displayed quite broad frequency functions, many of which showed multiple peaks. Figure 6 shows three examples which were obtained in a single penetration through the central nucleus of the IC. The first curve is of the simple type. The second and third, encountered at progressively deeper locations, are of the "W" type. Figure 7 illustrates the broad and complex tuning curves of two central nucleus units which were recorded simultaneously from the same location. The units were differentiated during data analysis by their distinct spike amplitudes. Note that, although one response is excitatory and the other suppressed, the frequency functions are similar in their general configuration.

The temporal response patterns of 30 of the 42 units changed with variations in stimulus frequency. A common mode of such change involved the appearance of discharge suppression immediately above and below the CF of the unit, a phenomenon associated with the "W" shaped iso-intensity frequency functions mentioned above. This type of response pattern variation was observed at all frequencies, although for CFs below approximately 0.6 kHz there was little or no suppression below CF. A second, and perhaps related variation was seen in units which displayed "primary-like" (Pfeiffer, 1966) response patterns at CF. In several such units, increase or decrease of stimulus frequency caused a decrease in late evoked discharge, leaving only an onset burst of discharges at the edges of the unit's response area. This type of response pattern variation was frequently observed in units with simple iso-intensity frequency functions. A third type of response pattern variation was seen only in units with CFs of 2 kHz


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Fig. 7. Iso-intensity frequency functions obtained from two single units at the same location in the central nucleus of the IC. Each point represents the mean discharge rate observed during ten nonperformance stimulus presentations at 80 dB SPL Analysis interval for the upper function was 0-75 msec, and for the lower function 75-200 msec after stimulus onset

o r b e l o w . In s ev e ra l such uni ts , phas i c o n s e t bu r s t s b e c a m e t h e d o m i n a n t f e a t u r e o f t h e r e s p o n s e p a t t e r n as s t imu lus f r e q u e n c y was i nc r ea sed . T h i s o f t e n i n v o l v e d

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Fig. 9. Discharge rate during the first 85 msec after stimulus onset as a function of stimulus intensity for unit SR 3 -1 , recorded from the central nucleus of the IC. Each point represents the mean of 30 nonperformance presentations of a pure tone at the unit's CF, 0.75 kHz. Vertical bars represent one standard deviation above and below each mean


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Fig. 11. Discharge rate from 0-75 msec after stimulus onset, as a function of stimulus intensity for unit SR 9-1, recorded in the central nucleus of the IC. Each point represents 14 stimulus presentations during reaction time performance. Vertical bars represent one standard deviation


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87 dB

| = | i i i a m m

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67 dB I , .

i i i

i i t i i

27 dB �9 l= .m.l= .= J - J i d . . . , , . . d . I . i .

100 200 300 4 0 500

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Fig. 13. PST histograms obtained with different intensities of a 1.3 kHz tone at the CF of unit SR 6-4. Each histogram represents 10 nonperformance stimulus presentations. Intensity given in dB SPL


20] | 90 dB

30- l 8O dB 20-

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20 7o dB

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Fig. 14. PST histograms obtained at several intensities of a 9.0 kHz pure tone at the CF of unit SR 3-5, from the central nucleus of the IC. Each histogram represents 30 nonperformance stimulus presentations. Intensity given in the dB SPL

Effect of Stimulus Intensity. Forty-nine units were examined at various stimulus intensities. Of this sample, 24 exhibited monotonic functions and 25 units displayed relationships between evoked discharge rate and stimulus intensity which deviated from monotonicity by greater than 10% of their maximal discharge rate. In some cases, this represented a simple deviation from an otherwise monotonic function. However , 17 of the 25 showed a distinct "best intensity" above and below which discharge rate was less than maximal.

Figure 9 shows a monotonic relationship between evoked discharge rate and stimulus intensity for a unit from the central nucleus of the IC, which was observed at its CF. Figure 10 illustrates a monotonic intensity function of another central nucleus unit in the form of PST histograms. Figures 11 and 1 2 are from nonmonotonic central nucleus units; one shows a function obtained with white noise stimulation (Fig. 11), the other shows PST histograms at various intensities of CF stimulation from another unit (Fig. 12). As can be seen from the histograms, the nonmonotonic function does not appear to result f rom an obvious suppressive component of the unit 's response pattern. Rather, the amplitude of the response decreases as a whole at intensities above 60 dB SPL.

The temporal response patterns of 42 of the 49 units showed significant change with variation in stimulus intensity. The most commonly observed patterns of this change were from a primary-l ike to a pause response pat tern (9/49), from a sustained elevation in discharge without an onset burst to a primary-l ike response (8/49, see Fig. 12), and a progression of response pat tern from sustained elevation in discharge to primary-l ike to pause (7/49) or further to a simple phasic onset burst (3/49). These changes involve the increasing prominence of brief-latency excitation and long-latency suppression with increasing stimulus intensity. Increases in the prominence of phasic onset


discharge with increase in intensity was also seen in units which displayed only inhibitory responses at low intensities (3/49) as illustrated in Figure 13. Increase in prominence of discharge suppression in a unit which exhibited only a phasic onset response at low intensities is illustrated in Figure 14. In a smaller number of units, phasic onset discharge at low intensities was combined with sustained elevation in discharge with increases in intensity (6/49), as in Figure 10. Response of Units in ICX. Only 13 units wet studied from ICX. On the basis of such a limited sample, little can be said regarding the characteristics of units in this division of the IC. The spontaneous rate of ICX units ranged from 1.22 to 32.22 discharges/sec, with a mean value of 10.4 discharges/sec. Initial latency of eight 1CX units, measured during performance under the conditions described above, ranged from 14.86 to 36.13 msec, with a mean of 25.14 msec. ICX unit latencies were appreciably longer than those from the central nucleus. The latencies of 36 central nucleus units during RT performance ranged from 4.72 to 31.17 msec, with a mean of 15.13 msec.

An iso-intensity function was obtained from only one ICX unit. It exhibited a phasic onset burst to stimuli from 0.1 to 30 kHz, at an intensity level 40 dB above its threshold at a CF of 0.3 kHz. A phasic offset burst was also elicited by stimuli between 0.1 an 0.3 kHz. A general impression, received from units not well isolated enough for reliable analysis and from background multiunit activity, was that ICX units were broadly tuned, without the narrow tuning often observed in the central nucleus. Six ICX units were examined at several stimulus intensities. Three intensity functions were monotonic, three nonmonotonic. Response pattern variation with changes in stimulus intensity was similar to that seen in the central nucleus.

Discussion

To summarize, IC units in the alert monkey displayed marked variations in temporal discharge pattern with variations in stimulus frequency and intensity. Most units displayed significant spontaneous discharge. Both broadly and narrowly tuned units were encountered in the central nucleus of the IC. Half of all units encountered displayed nonmonotonic relationships between evoked discharge rate and stimulus intensity.

The changes in temporal response pattern which we observed with changes in stimulus frequency and intensity have been reported by other investigators (Rose et al., 1963; Geisler et al., 1969; Stillman, 1971). The proportion of our units which exhibited such changes in pattern was high (76 %) and it is probable that if sufficient stimulus parameters had been varied in each case, all units would have exhibited some form of response pattern variation. As was pointed out by Stillman (1971), such variability makes the classification of units by response pattern difficult, if not impossible. However, this prevalence of response pattern variation is not surprising. It is reasonable to assume that changes in stimulus parameters lead to changes in the pattern of inputs to IC cells, and thus to variation in temporal firing pattern. In the IC units which we studied, the variation in response pattern was often orderly, and certain


common trends were observed. The types of response pattern variation which we observed have implications for the manner in which IC units receive input from other portions of the auditory pathway.

Nelson and Erulker (1963) have described, on the basis of intracellular recordings, a sequence of events evoked by tonal stimulation in neurons of the IC of the anesthetized cat. At high stimulus intensities, the onset of tonal stimulation evoked short-latency excitatory postsynaptic potentials (EPSPs) and associated cell discharge. At longer latencies, both EPSPs and inhibitory postsynaptic potentials (IPSPs) were observed. With decreases in stimulus intensity toward threshold, both the short-latency EPSPs and the long-latency IPSPs disappeared before the long-latency EPSPs. This pattern of synaptic events was common, though not universal. Further evidence that the interplay of inhibitory and excitatory events determines the temporal response patterns of units in the IC comes from the work of Watanabe and Simada (1971), who demonstrated that the phasic onset response of some IC units could be converted into a sustained discharge response by the in situ microinjection of picrotoxin. This suggests that presynaptic inhibition plays a role in determining the response characteristics of IC units. The patterns of synaptic events implied by the above investigations are consistent with the intensity-related changes which we observed in many cells of the IC of the alert monkey. The combination of low threshold, long-latency excitatory input with higher threshold, short- latency excitatory and long-latency inhibitory inputs would account for the commonly observed increasing dominance of phasic onset discharge and sustained discharge suppression with increasing stimulus intensity.

While Nelson and Erulkar (1963) also reported that EPSP and IPSP patterns changed with changes in stimulus frequency, they did not report any consistent pattern which would relate these changes either to absolute frequency or to unit CF. Our data indicate such a pattern. If one assumes that primary-like temporal response patterns represent input from VIIIth nerve fibers which has been influenced to a relatively small degree by central processing, then it is apparent that such input is important near and/or below the CF of many IC units. Changes in stimulus frequency away from CF appear to produce in most IC units either a decrease in later excitatory input or, more probably, an increase in stimulus-evoked inhibitory input. Depending upon latency and duration, these changes could account for " W " shaped iso-intensity rate functions (development of a brief latency inhibition) or the progression from primary-like to pause to pure onset response (development of inhibition evoked with a latency of 50-75 msec). The observation that units with CFs below 2 kHz displayed a progression of response patterns from primary-like to pause to phasic onset response with increasing stimulus frequency, suggests a relationship between stimulus frequency and the amount of inhibition evoked with a latency of 50-75 msec.

Chronic recording in alert, performing animals is the only means by which the activity of auditory single units may be evaluated when they are actually called upon to perform in hearing. Concomitantly, with chronic recording we can assess the degree to which unit data recorded from acute preparations are influenced by anesthesi a , and thus the degree to which such data can be


generalized to the auditory system in its normal, functional state. The results of this study are in agreement with previous findings that the behavior of single units in unanesthetized preparations is different from that observed in the anesthetized animal (Miller et al., 1972; Bock et al., 1972; Pfingst et al., 1977). However, the differences seen were not as extensive as those reported by some previous investigators.

The many nonmonotonic intensity functions which were observed in the IC of the unanesthetized rhesus monkey are consistent with observations in the anesthetized cat (Rose et al., 1963). Such intensity functions may reflect increases in inhibition, as inferred from the changes in response patterns with increasing intensity discussed above. The observation of both broadly and narrowly tuned units in our IC sample consistent with reports from anesthetized cat (Erulkar, 1959; Rose et al., 1963). Both of these findings are in conflict with the report of Bock et al. (1972) that single units in the IC of the alert cat displayed monotonic intensity functions and uniformly broad frequency responses. The spontaneous rates of discharge of IC units in our sample are significantly higher than those reported from anesthetized cat (Rose et al., 1963; Nelson and Erulkar, 1963), and similar to those reported by Bock et al. (1972) from the alert cat. While Bock et al. reported no spontaneous rates below 2/sec and we observed several units with rates between 0/sec and 1/sec, this may reflect Bock et al.'s small sample size (n = 26).

The reason for the disparities between our work and that of Bock et al. is not clear. Since our data are consistent with many reports from anesthetized cat, a species difference seems unlikely. Bock et al. attributed the differences between their data and previous reports from anesthetized cat to anesthetic depression of unit responsiveness. They proposed that anesthesia selectively depresses excitatory responses, and thus enhances the importance of inhibitory inputs to IC neurons. This would result in low spontaneous rates, narrow tuning curves and inhibitory dominance at high stimulus intensities (nonmonotonic intensity functions). Our data support the concept of anesthetic depression of spontaneous rate. However, they do not support the extent of anesthetic effects implied by Bock et al.'s report. In particular, the high proportion of nonmonotonic intensity functions seen in our unit sample and the narrow frequency responses clearly demonstrate that these phenomena are not an artifact produced by anesthetic depression of normal IC unit function. This is supported by the observations of Pfingst et al. (1977) in the auditory cortex of the monkey in which anesthetics and sleep-waking state were found to exert relatively modest influcence upon response area, and of Evans and Nelson (1973), who found that anesthesia exerted a greater influence upon inhibitory than upon excitatory unit responses in the cochlear nucleus of the cat.

Webster and Veale (1971) and Aitkin et al. (1972) have reported that the discharge characteristics of units recorded in the ICX are quite distinct from those observed in the central nucleus of the IC. In particular, they cited rapid habituation of unit responses to repetitive stimuli in the ICX, with little habituation seen in the central nucleus. No significant habituation was noted in our admittedly small sample of ICX units. This may be related to our use of trained, alert monkeys. This preparation has been reported to greatly decrease


the hab i tua t ion of audi tory cortical uni ts to simple, repet i t ive st imuli (Miller et al., 1972). Our results do no t suppor t a special role for the ICX in a t tent ion, as has been suggested by the above authors. However , the relat ively long latencies of our ICX units as compared to centra l nucleus units is cons is tent with a less direct origin of the audi tory input to the cells of this division, as has been suggested by Webs te r and Ai tk in (1975).

The tonotopic organiza t ion which we observed in the m o n k e y is essential ly

similar to that seen in the cat by Rose et al. (1963). The pos te ro -an te r io r tonotopic a r r angemen t which we e n c o u n t e r e d is p robab ly due only in part to the ro ta t ion of the IC in the seated m o n k e y (Smith et al., 1972), and is suggestive of observat ions by Katsuki et al. (1958) in the cat. It is in conflict with D ixon ' s (1973) repor t of an an te ro -pos te r io r tonotopic a r r angemen t also in the cat.

References

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Dixon, N.T.: Tonotopic organization of the inferior colliculus and the effects of lateral lemniscus lesions on hearing sensitivity in the cat. Unpublished Ph.D. dissertation, Univ. of Indiana (1973)

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Pollack, G., Marsh, D., Bodenhamer, R., Souther, A.: Echo-detecting characteristics of neurons in inferior colliculus of unanesthetized bats. Science 196, 675-678 (1977)

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Ryan, A. F., Miller, J.M.: Effects of behavioral performance on single-unit firing patterns in inferior colliculus of the rhesus monkey. J. Neurophysiol. 40, 943-956 (1977)

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Received August 16, 1977

single unit responses in the inferior colliculus of the awake and performing rhesus monkey

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