Paradoxical Latency Shift Research Articles

Topography of sound level representation in the FM sweep selective region of the pallid bat auditory cortex

Sound level processing is a fundamental function of the auditory system. To determine how the cortex represents sound level, it is important to quantify how changes in level alter the spatiotemporal structure of cortical ensemble activity. This is particularly true for echolocating bats that have control over, and often rapidly adjust, call level to actively change echo level. To understand how cortical activity may change with sound level, here we mapped response rate and latency changes with sound level in the auditory cortex of the pallid bat. The pallid bat uses a 60-30 kHz downward frequency modulated (FM) sweep for echolocation. Neurons tuned to frequencies between 30 and 70 kHz in the auditory cortex are selective for the properties of FM sweeps used in echolocation forming the FM sweep selective region (FMSR). The FMSR is strongly selective for sound level between 30 and 50 dB SPL. Here we mapped the topography of level selectivity in the FMSR using downward FM sweeps and show that neurons with more monotonic rate level functions are located in caudomedial regions of the FMSR overlapping with high frequency (50–60 kHz) neurons. Non-monotonic neurons dominate the FMSR, and are distributed across the entire region, but there is no evidence for amplitopy. We also examined how first spike latency of FMSR neurons change with sound level. The majority of FMSR neurons exhibit paradoxical latency shift wherein the latency increases with sound level. Moreover, neurons with paradoxical latency shifts are more strongly level selective and are tuned to lower sound level than neurons in which latencies decrease with level. These data indicate a clustered arrangement of neurons according to monotonicity, with no strong evidence for finer scale topography, in the FMSR. The latency analysis suggests mechanisms for strong level selectivity that is based on relative timing of excitatory and inhibitory inputs. Taken together, these data suggest how the spatiotemporal spread of cortical activity may represent sound level.

Footprints of inhibition in the response of cortical delay-tuned neurons of bats

Responses of echo-delay-tuned neurons that encode target distance were investigated in the dorsal auditory cortex of anesthetized short-tailed fruit bats (Carollia perspicillata). This species echolocates using short downward frequency-modulated (FM) biosonar signals. In response to FM sweeps of increasing level, 60 out of 131 studied neurons (47%) displayed a "paradoxical latency shift," i.e., longer response latency to loud sounds and shorter latency to faint sounds. In addition, a disproportionately large number of neurons (80%) displayed nonmonotonic responses, i.e., weaker responses to loud sounds and stronger responses to faint sounds. We speculate that the observed paradoxical latency shift and nonmonotonic responses are extracellular footprints of inhibitory processes evoked by loud sounds and that they could represent a specialization for the processing of the emitted loud biosonar pulse. Supporting this idea is the fact that all studied neurons displayed strong response suppression when an artificial loud pulse and a faint echo were presented together at a nonoptimal delay. In 24 neurons, iontophoresis of bicuculline (an antagonist of A-type γ-aminobutyric acid receptors) did not remove inhibitory footprints but did increase the overall spike output, and in some cases it also modified the response bandwidth and shifted the neuron's "best delay." We suggest that inhibition could play a dual role in shaping delay tuning in different auditory stations. Below the cortex it participates in delay-tuning implementation and leaves a footprint that is measurable in cortical responses, while in the cortex it provides a substrate for an in situ control of neuronal selectivity.

Sound-evoked oscillation and paradoxical latency shift in the inferior colliculus neurons of the big fruit-eating bat, Artibeus jamaicensis

Frequency tuning, temporal response pattern and latency properties of inferior colliculus neurons were investigated in the big fruit-eating bat, Artibeus jamaicensis. Neurons having best frequencies between 48-72kHz and between 24-32kHz are overrepresented. The inferior colliculus neurons had either phasic (consisting in only one response cycle at all stimulus intensities) or long-lasting oscillatory responses (consisting of multiple response cycles). Seventeen percent of neurons displayed paradoxical latency shift, i.e. their response latency increased with increasing sound level. Three types of paradoxical latency shift were found: (1) stable, that does not depend on sound duration, (2) duration-dependent, that grows with increasing sound duration, and (3) progressive, whose magnitude increases with increasing sound level. The temporal properties of paradoxical latency shift neurons compare well with those of neurons having long-lasting oscillatory responses, i.e. median inter-spike intervals and paradoxical latency shift below 6ms are overrepresented. In addition, oscillatory and paradoxical latency shift neurons behave similarly when tested with tones of different durations. Temporal properties of oscillation and PLS found in the IC of fruit-eating bats are similar to those found in the IC of insectivorous bats using downward frequency-modulated echolocation calls.

Neural mechanisms of target ranging in FM bats: physiological evidence from bats and frogs

Echolocating bats assess target range by the delay in echo relative to the emitted sonar pulse. Earlier studies in FM bats showed that a population of neurons in auditory centers above the inferior colliculus (IC) is tuned to echo delay, with different neurons tuned to different echo delays. A building block for delay-tuned responses is paradoxical latency shift (PLS), featuring longer response latencies to more intense sounds. PLS is first created in the IC, where neurons exhibit unit-specific quantum increase in response latency with increasing sound level. Other IC neurons display oscillatory discharges whose period is unit-specific and level tolerant, indicating that this is attributable to cell's intrinsic properties. High-threshold inhibition of oscillatory discharge produces PLS, indicating that oscillatory discharge is a building block for PLS. To investigate the cellular basis of oscillatory discharges, we performed whole-cell patch-clamp recordings from IC neurons in leopard frogs (which also exhibit oscillatory discharges and PLS). These recordings show that IC neurons are heterogeneous displaying diverse biophysical phenotypes; each phenotype (and cell) has its own membrane time constant, input resistance, and strengths of I(h), I(kir), I(kv)--these intrinsic properties give rise to cell-specific resonance which can be observed through current and afferent stimulations.

Corticofugal Modulation of the Paradoxical Latency Shifts of Inferior Collicular Neurons

The central auditory system creates various types of neurons tuned to different acoustic parameters other than a specific frequency. The response latency of auditory neurons typically shortens with an increase in stimulus intensity. However, approximately 10% of collicular neurons of the little brown bat show a "paradoxical latency-shift (PLS)": long latencies to intense sounds but short latencies to weak sounds. These neurons presumably are involved in the processing of target distance information carried by a pair of an intense biosonar pulse and its weak echo. Our current studies show that collicular PLS neurons of the big brown bat are modulated by the corticofugal (descending) system. Electric stimulation of cortical auditory neurons evoked two types of changes in the PLS neurons, depending on the relationship in the best frequency (BF) between the stimulated cortical and recorded collicular neurons. When the BF was matched between them, the cortical stimulation did not shift the BFs of the collicular neurons and shortened their response latencies at intense sounds so that the PLS became smaller. When the BF was unmatched, however, the cortical stimulation shifted the BFs of the collicular neurons and lengthened their response latencies at intense sounds, so that the PLS became larger. Cortical electric stimulation also modulated the response latencies of non-PLS neurons. It produced an inhibitory frequency tuning curve or curves. Our findings indicate that corticofugal feedback is involved in shaping the spectrotemporal patterns of responses of subcortical auditory neurons presumably through inhibition.

Timing of sound-evoked potentials and spike responses in the inferior colliculus of awake bats

Neurons in the inferior colliculus (IC), one of the major integrative centers of the auditory system, process acoustic information converging from almost all nuclei of the auditory brain stem. During this integration, excitatory and inhibitory inputs arrive to auditory neurons at different time delays. Result of this integration determines timing of IC neuron firing. In the mammalian IC, the range of the first spike latencies is very large (5–50 ms). At present, a contribution of excitatory and inhibitory inputs in controlling neurons' firing in the IC is still under debate. In the present study we assess the role of excitation and inhibition in determining first spike response latency in the IC. Postsynaptic responses were recorded to pure tones presented at neuron's characteristic frequency or to downward frequency modulated sweeps in awake bats. There are three main results emerging from the present study: (1) the most common response pattern in the IC is hyperpolarization followed by depolarization followed by hyperpolarization, (2) latencies of depolarizing or hyperpolarizing responses to tonal stimuli are short (3–7 ms) whereas the first spike latencies may vary to a great extent (4–26 ms) from one neuron to another, and (3) high threshold hyperpolarization preceded long latency spikes in IC neurons exhibiting paradoxical latency shift. Our data also show that the onset hyperpolarizing potentials in the IC have very small jitter (<100 μs) across repeated stimulus presentations. The results of this study suggest that inhibition, arriving earlier than excitation, may play a role as a mechanism for delaying the first spike latency in IC neurons.

FM signals produce robust paradoxical latency shifts in the bat’s inferior colliculus

Previous studies in echolocating bats, Myotis lucifugus, showed that paradoxical latency shift (PLS) is essential for neural computation of target range and that a number of neurons in the inferior colliculus (IC) exhibit unit-specific PLS (characterized by longer first-spike latency at higher sound levels) in response to tone pulses at the unit's best frequency. The present study investigated whether or not frequency-modulated (FM) pulses that mimic the bat's echolocation sonar signals were equally effective in eliciting PLS. For two-thirds of PLS neurons in the IC, both FM and tone pulses could elicit PLS, but only FM pulses consistently produced unit-specific PLS. For the remainder of PLS neurons, only FM pulses effectively elicited PLS; these cells showed either no PLS or no response, to tone pulses. PLS neurons generally showed more pronounced PLS in response to narrow-band FM (each sweeping 20 kHz in 2 ms) pulse that contained the unit's best frequency. In addition, almost all PLS neurons showed duration-independent PLS to FM pulses, but the same units exhibited duration-dependent PLS to tone pulses. Taken together, when compared to tone pulses, FM stimuli can provide more reliable estimates of target range.

Leading Inhibition to Neural Oscillation Is Important for Time-Domain Processing in the Auditory Midbrain

A number of central auditory neurons exhibit paradoxical latency shift (PLS), a response characterized by longer response latencies at higher sound levels. PLS neurons are known to play a role in target ranging for echolocating bats that emit frequency-modulated sounds. We recently reported that early inhibition of unit's oscillatory discharges is critical for PLS in the inferior colliculus (IC) of little brown bats. The goal of this study was to determine in echolocating bats and in non-echolocating animals (frogs): 1) the detailed characteristics of PLS and whether PLS was dependent on sound level, frequency, and duration; 2) the time course of inhibition underlying PLS using a paired-pulse paradigm. We found that 22% of IC neurons in bats and 15% in frogs exhibited periodic discharge patterns in response to tone pulses at high sound levels. The firing periodicity was unit specific and independent of sound level and duration. Other IC neurons (28% in bats; 14% in frogs) exhibited PLS. These PLS neurons shared several response characteristics: 1) PLS was largely independent of sound frequency and 2) the magnitude of shift in first-spike latency was either duration dependent or duration tolerant. For PLS neurons, application of bicuculline abolished PLS and unmasked the unit's periodical firing pattern that served as the building block for PLS. In response to paired sound pulses, PLS neurons exhibited delay-dependent response suppression, confirming that high-threshold leading inhibition was responsible for PLS. Results also revealed the timing of excitatory and inhibitory inputs underlying PLS and its role in time-domain processing.

FM signals produce a robust paradoxical latency shift that is important for coding of target range in the bat inferior colliculus

Echolocating bats utilize the time delay between an outgoing ultrasonic pulse and its echo to determine target range. Many neurons at the inferior colliculus (IC) and above are tuned to time delays between these sound pulses of unequal amplitudes. Sullivan previously proposed that paradoxical latency shift (PLS), characterized by a quantal increase in firing latency to loud sounds, is important for this attribute because PLS permits coincidence detection that is important for the creation of delay-tuned responses. In the IC of little brown bats, Galazyuk and Feng recently reported that, in response to tone pulses, the proportion of neurons showing PLS was low (&amp;lt;20%). This study was undertaken to determine whether PLS is a function of the acoustic stimulus. For this, the temporal discharge patterns of single IC neurons were investigated over a broad range of sound levels, using tone pulses at CF as well as FM sound pulses that mimicked bats’ ultrasonic cry as stimuli. For many IC neurons, tone pulses did not elicit PLS but FM sound pulses produced robust PLS. This result showed that PLS is stimulus dependent and that the bat’s auditory system is optimal for processing FM sounds employed during echolocation. [Work supported by NIH R01DC04998.]

Oscillation May Play a Role in Time Domain Central Auditory Processing

To study how sound intensity altered the temporal response pattern of a unit, we recorded from 92 single neurons in the inferior colliculus (IC) of the little brown bat and investigated their firing patterns in response to brief tone pulses (2 msec duration) at the characteristic frequency of the unit over a wide dynamic range (10-90 dB sound pressure level). We found two unusual response characteristics at high sound levels in approximately one-third of the IC neurons investigated. For 16 IC neurons (17%), an increase in sound level not only elicited a shorter response latency and an increase in spike count but also transformed the firing pattern of the unit from phasic to periodic; this pattern was more pronounced at higher sound levels. The firing periodicity was unit specific, ranging from 1.3 to 6.7 msec. Twenty-seven IC neurons (29%) exhibited a longer response latency at higher sound levels compared with lower sound levels [i.e., paradoxical latency shift (PLS)]. The majority of this population showed a one or more quantum increase in latency when sound level was elevated. The quantum shift was also unit specific, ranging from 1.2 to 8.2 msec. We further investigated the firing patterns of 14 IC neurons showing PLS before, during, and after iontophoretic application of bicuculline. For 12 of these neurons, drug application abolished the PLS and transformed the firing patterns of the unit at high sound levels from phasic into sustained periodic discharges. Our results suggest that neural oscillation in combination with ordinary inhibition may be responsible for the creation of PLSs shown previously to be important for temporal information processing.

Roles of neural oscillation in time domain processing in the bat inferior colliculus

Central auditory neurons in echolocating bats exhibit pulse-echo delay-tuned responses. Sullivan (1982) proposed that paradoxical latency shift (PLS), characterized by an increase in response latency to loud sounds, is important for this attribute. At present, the mechanism underlying PLS is unclear. The goal of the present study was to identify the mechanism underlying PLS. The responses of 92 neurons in the inferior colliculus of little brown bats to brief tone pulses at the unit’s CF over a wide range of sound levels were studied. Of these, 16 neurons displayed unit-specific periodic oscillatory discharges at high sound levels with a characteristic period of 1.3–6.7 ms. The 27 neurons exhibited unit-specific PLS, with quantal latency shift of 1.2–8.2 ms. In 14 neurons showing PLS, unit’s responses before, during and after iontophoretic application of bicuculline were investigated. Application of bicuculline abolished the PLS and transformed it into periodic discharges, suggesting that neural oscillation in combination with ordinary inhibition may be responsible for PLS. To further investigate whether intrinsic neural property was responsible for PLS, unit’s responses to sounds having different durations were investigated. The result indicates that both intrinsic and extrinsic mechanisms are likely involved in creation of PLS. [Work supported by NIH R01DC00663.]

Echo SPL influences the ranging performance of the big brown bat, Eptesicus fuscus

Four bats of the species Eptesicus fuscus were trained in a two-alternative forced-choice procedure to discriminate between two phantom targets that differed in range. The rewarded stimulus was located at a distance of 52.7 cm, while the other unrewarded stimulus was further away. Only one target was presented at a time. In the first experiment we measured the range discrimination performance at an echo SPL of -28 dB relative to the bat's sonar transmission. A 75% correct performance level was arbitrarily defined as threshold and was obtained at a delay difference of 80 microseconds, corresponding to a range difference of 13.8 mm. In the second experiment the delay difference was fixed at 150 microseconds and the echo SPL varied between -8 and -48 dB relative to sonar emissions. The performance of the bats depended on the relative echo SPL. AT -28 dB the bats showed the best performance. It deteriorated at an increase of the relative echo SPL to -18 dB and -8 dB. The performance also deteriorated when the relative echo SPL was reduced to -38 dB and -48 dB. Only at low relative echo SPLs did the bats partially compensate for the reduction in echo SPL and increased the SPL of their emitted signals by a few dB. Our results support the hypothesis that neurons exhibiting paradoxical latency shift may be involved in encoding target range. This hypothesis predicts a decrease in performance at high echo SPLs as we found it in our experiments. The observed reduction in performance at very low echo SPLs may be due to a decrease in S/N ratio.

Possible neural mechanisms of target distance coding in auditory system of the echolocating bat Myotis lucifugus.

1. In order to investigate the possible neural mechanisms underlying delay-dependent facilitation in the bat's auditory cortex (18), the responses to single FM pulses of varying amplitude were examined. Analysis of amplitude-spike count functions revealed three distinct types: monotonic, simple nonmonotonic, and complex nonmonotonic. The complex nonmonotonic function had two separate amplitude peaks, with a clear notch or worst amplitude between them. Other units had spike count functions that were mainly monotonic or nonmonotonic, but showed some evidence for a second response region. 2. Examination of response latency revealed another novel response property, which has been termed the paradoxical latency shift. Units with this response property responded at a shorter latency to sounds of low amplitude than to sounds of high amplitude. The paradoxical latency shift also appears to be related to the twin-peaked complex nonmonotonic response function. Units with the most prominent twin-peaked response functions also had the clearest latency shifts. In these units, the high-amplitude peak corresponded to the long-latency response and the low-amplitude peak to the short-latency-response. 3. These curious spike count and latency observations can be explained if they are considered in relation to the temporal and amplitude pattern of the acoustic input during echolocation. In echolocation, a loud orientation pulse is followed by a weaker echo. In delay-dependent facilitation, this pulse-echo sequence is followed by a neural response if the pulse-echo delay is appropriate. The simplest model for delay-dependent facilitation assumes that a synchronization of excitatory inputs from the pulse and echo is needed for facilitation. Since the weaker echo occurs after the pulse, it is closer in time to the postulated synchronization point. Therefore, in order for this model to work, the echo input must reach the summation place with less of a time lag than the pulse input. This is exactly what is seen with the paradoxical latency shift; the loud "pulse" response is delayed relative to the weak "echo" response.