Delay-tuned Neurons Research Articles

Oscillatory discharges in the auditory midbrain of the big brown bat contribute to coding of echo delay.

Subsequent to his breakthrough discovery of delay-tuned neurons in the bat's auditory midbrain and cortex, Albert Feng proposed that neural computations for echo delay involve intrinsic oscillatory discharges generated in the inferior colliculus (IC). To explore further the presence of these neural oscillations, we recorded multiple unit activity with a novel annular low impedance electrode from the IC of anesthetized big brown bats and Seba's short-tailed fruit bats. In both species, responses to tones, noise bursts, and FM sweeps contain long latency components, extending up to 60ms post-stimulus onset, organized in periodic, oscillatory-like patterns at frequencies of 360-740Hz. Latencies of this oscillatory activity resemble the wide distributions of single neuron response latencies in the IC. In big brown bats, oscillations lasting up to 30ms after pulse onset emerge in response to single FM pulse-echo pairs, at particular pulse-echo delays. Oscillatory responses to pulses and evoked responses to echoes overlap extensively at short echo delays (5-7ms), creating interference-like patterns. At longer echo delays, responses are separately evident to both pulses and echoes, with less overlap. These results extend Feng's reports of IC oscillations, and point to different processing mechanisms underlying perception of short vs long echo delays.

Unexpected Rule-Changes in a Working Memory Task Shape the Firing of Histologically Identified Delay-Tuned Neurons in the Prefrontal Cortex

Working memory-guided behaviors require memory retention during delay periods, when subsets of prefrontal neurons have been reported to exhibit persistently elevated firing. What happens to delay activity when information stored in working memory is no longer relevant for guiding behavior? In this study, we perform juxtacellular recording and labeling of delay-tuned (-elevated or -suppressed) neurons in the prelimbic cortex of freely moving rats, performing a familiar delayed cue-matching-to-place task. Unexpectedly, novel task-rules are introduced, rendering information held in working memory irrelevant. Following successful strategy switching within one session, delay-tuned neurons are filled with neurobiotin for histological analysis. Delay-elevated neurons include pyramidal cells with large heterogeneity of soma-dendritic distribution, molecular expression profiles, and task-relevant activity. Rule change induces heterogenous adjustments on individual neurons and ensembles' activity but cumulates in balanced firing rate reorganizations across cortical layers. Our results demonstrate divergent cellular and network dynamics when an abrupt change in task rules interferes with working memory.

Thalamic projections sustain prefrontal activity during working memory maintenance.

The mediodorsal thalamus (MD) shares reciprocal connectivity with the prefrontal cortex (PFC) and decreased MD-PFC connectivity is observed in schizophrenia patients. Patients also display cognitive deficits including impairments in working memory, but a mechanistic link between thalamo-prefrontal circuit function and working memory is missing. Here, using pathway-specific inhibition we found directional interactions between MD and medial PFC (mPFC), with MD-to-mPFC supporting working memory maintenance and mPFC-to-MD supporting subsequent choice. We further identify mPFC neurons that display elevated spiking during the delay, a feature that was absent on error trials and required MD inputs for sustained maintenance. Strikingly, delay-tuned neurons had minimal overlap with spatially-tuned neurons and each mPFC population exhibited mutually exclusive dependence on MD and hippocampal inputs. These findings indicate a role for the MD in sustaining prefrontal activity during working memory maintenance. Consistent with this idea we found that enhancing MD excitability was sufficient to enhance task performance.

Acuity in ranging based on delay-tuned combination-sensitive neurons in the auditory cortex of mustached bats

A 1.0-ms echo delay from an emitted bio-sonar pulse at 25 °C corresponds to a 17.3-cm target distance. In the auditory cortex of the mustached bat, Pteronotus parnellii, neurons tuned to a specific delay (best delay) of an echo from an emitted pulse are clustered in the FF, dorsal fringe and ventral fringe areas. (“FF” stands for the frequency-modulated components of a pulse and its echo.) Those delay-tuned neurons are systematically arranged in the FF area according to their best delays and form a 18-ms-long delay axis. Using the neurophysiological data, the theoretical acuity at a 75% correct level was computed as just-noticeable changes in (a) the location of maximally responding delay-tuned neurons, (b) the location of the center of all responses in the FF area, and (c) the weighted sum of responses of all delay-tuned neurons. The acuity is range-dependent: the shorter the target range, the higher the acuity is. The just-noticeable changes in target range are 7.57–46.2, 0.50–2.32 and 0.22–2.53 mm at the target ranges of up to 140 cm for (a), (b) and (c), respectively. When the dorsal and ventral fringe areas are included in the computation, the just-noticeable changes become smaller than those in the FF area alone. Those acuities computed are comparable to certain behavioral acuities.

Echo-level compensation and delay tuning in the auditory cortex of the mustached bat.

During echolocation, bats continuously perform audio-motor adjustments to optimize detection efficiency. It has been demonstrated that bats adjust the amplitude of their biosonar vocalizations (known as 'pulses') to stabilize the amplitude of the returning echo. Here, we investigated this echo-level compensation behaviour by swinging mustached bats on a pendulum towards a reflective surface. In such a situation, the bats lower the amplitude of their emitted pulses to maintain the amplitude of incoming echoes at a constant level as they approach a target. We report that cortical auditory neurons that encode target distance have receptive fields that are optimized for dealing with echo-level compensation. In most cortical delay-tuned neurons, the echo amplitude eliciting the maximum response matches the echo amplitudes measured from the bats' biosonar vocalizations while they are swung in a pendulum. In addition, neurons tuned to short target distances are maximally responsive to low pulse amplitudes while neurons tuned to long target distances respond maximally to high pulse amplitudes. Our results suggest that bats dynamically adjust biosonar pulse amplitude to match the encoding of target range and to keep the amplitude of the returning echo within the bounds of the cortical map of echo delays.

Temporal encoding precision of bat auditory neurons tuned to target distance deteriorates on the way to the cortex.

During echolocation, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. In the bat's auditory system, echo delay-tuned neurons that only respond to pulse-echo pairs having a specific echo delay serve target distance calculation. Accurate prey localization should benefit from the spike precision in such neurons. Here we show that delay-tuned neurons in the inferior colliculus of the mustached bat respond with higher temporal precision, shorter latency and shorter response duration than those of the auditory cortex. Based on these characteristics, we suggest that collicular neurons are best suited for a fast and accurate response that could lead to fast behavioral reactions while cortical neurons, with coarser temporal precision and longer latencies and response durations could be more appropriate for integrating acoustic information over time. The latter could be important for the formation of biosonar images.

Synaptic mechanisms shaping delay-tuned combination-sensitivity in the auditory thalamus of mustached bats

For the processing of target-distance information, delay-tuned auditory neurons of the mustached bat show facilitative responses to a combination of signal elements of a biosonar pulse-echo pair with a specific echo delay. They are initially produced in the inferior colliculus by facilitative responses based on the coincidence of the rebound response following glycinergic inhibition to the first harmonic of the pulse and a short-latency response to the 2nd–4th harmonics of its echo. Here, we report that further facilitative responses to pulse-echo pairs of thalamic delay-tuned neurons are mediated by glutamate receptors (NMDA and non-NMDA receptors), and that GABAergic inhibition shortens the duration of facilitative responses mediated by NMDA-receptors, without changing the delay tuning of thalamic delay-tuned neurons. Different from collicular delay-tuned neurons, thalamic ones respond much more to pulse-echo pairs than individual signal elements. The neural mechanisms involved in shaping thalamic delay-tuning support a model of hierarchical signal processing in the auditory system.

Albert Feng and target ranging by echolocating bats

Ultrasonic biosonar sounds propagate out to a target and return as echoes. Simultaneously, phasic-on neural responses evoked by each outbound sound propagate from one subpopulation of neurons to another at different latencies in the inferior colliculus, creating delay-lines carrying a replica of the broadcast. When each echo returns, it evokes new on-responses that travel over similar subpopulations of neurons, but lagging behind responses to the broadcast according to the delay of the echo. Albert Feng’s discovery of delay-tuned neurons in the bat’s nucleus intercollicularis revealed that bats “read out” echo delay from the delay-lines by detecting the succession of coincidences between responses to the echo and to the emission. Subsequent work in multiple labs demonstrated the ubiquity of delay-tuning in bats. Working in the inferior colliculus, Al Feng showed how the delay-line responses are restricted to single spikes by initial inhibition that determines each neuron’s characteristic on-response latency followed by new inhibition that suppresses any subsequent multiple spikes. The interplay between timed and triggered inhibition defines the delay-lines, while delay-tuned coincidence-detecting neurons from inferior colliculus to superior colliculus guide the bat and from inferior colliculus to auditory cortex create the bat’s perceived images. [Work supported by ONR.]

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.

Neurons in the inferior colliculus of the mustached bat are tuned both to echo-delay and sound duration

Echolocation in bats requires a precise temporal processing of complex signals. This processing of time includes the encoding of echo-delay, which gives an estimation of target distance, and sound duration, which is considered to be important for own sound or echo recognition. In this study, we report that delay-tuned neurons in the inferior colliculus of the mustached bat (Pteronotus parnellii) are also tuned to sound duration. Collicular delay-tuned neurons showed three types of duration tuning: short-pass (12 of 64), band-pass (16 of 64), and long-pass (17 of 64). The remaining 19 delay-tuned neurons are not selective for sound duration. All short-pass and 10 band-pass neurons' characteristic delays were similar to characteristic duration. In six band-pass neurons, characteristic delay was different from characteristic duration. Neurons processing unmatched delay and durations could be participating in complex kinds of processing where the same neuron has different functions depending on the activated neural network.

Properties of echo delay-tuning receptive fields in the inferior colliculus of the mustached bat

One role of the inferior colliculus (IC) in bats is to create neuronal delay-tuning, which is used for the estimation of target distance in the echolocating bat’s auditory system. In this study, we describe response properties of IC delay-tuned neurons of the mustached bat (Pteronotus parnellii) and compare it with those of delay-tuned neurons of the auditory cortex (AC). We also address the question if frequency content of the stimulus (pure-tone (PT) or frequency-modulated (FM) pairs stimulation) affects combination-sensitive interaction in the same neuron. Sharpness and sensitivity of delay-tuned neurons in the IC are similar to those described in the AC. However, in contrast to cortical responses, in collicular neurons the delay at which the neurons show the maximum response does not change with changes in echo level. This tolerance to changes in the echo level seems to be a property of collicular delay-tuned neurons, which is modified along the ascending auditory pathway. In the IC we found neurons that showed a facilitated delay-tuned response when stimulated with FM components and did not show any delay-tuning with PT stimulation. This result suggests that not only is echo delay-tuning generated in the IC but also its FM-specificity observed in the cortex could be created to some extent in the IC and then topographically organized at higher levels.

Auditory cortex of newborn bats is prewired for echolocation

Neuronal computation of object distance from echo delay is an essential task that echolocating bats must master for spatial orientation and the capture of prey. In the dorsal auditory cortex of bats, neurons specifically respond to combinations of short frequency-modulated components of emitted call and delayed echo. These delay-tuned neurons are thought to serve in target range calculation. It is unknown whether neuronal correlates of active space perception are established by experience-dependent plasticity or by innate mechanisms. Here we demonstrate that in the first postnatal week, before onset of echolocation and flight, dorsal auditory cortex already contains functional circuits that calculate distance from the temporal separation of a simulated pulse and echo. This innate cortical implementation of a purely computational processing mechanism for sonar ranging should enhance survival of juvenile bats when they first engage in active echolocation behaviour and flight.

Comparison of properties of cortical echo delay-tuning in the short-tailed fruit bat and the mustached bat

Target-distance computation by cortical neurons sensitive to echo delay is an essential characteristic of the auditory system of insectivorous bats. To assess if functional requirements such as detection of small insects versus larger stationary surfaces of plants are reflected in cortical properties, we compare delay-tuned neurons in a frugivorous (C. perspicillata, CP) and an insectivorous (P. parnellii, PP) bat species that belong to related families within the superfamily of Noctilionoidea. The bandwidth and shape of delay-tuning curves and the range of characteristic delays are similar in both species and hence are not related to different echolocation strategies. Most units respond at 2-6 ms echo delay with most sensitive thresholds of 20-30 dB SPL. In CP, units tuned to delays >12 ms are slightly more abundant and are more sensitive than in PP. All delay-tuned neurons in CP reliably respond to single pure-tone stimuli, whereas such responses are only observed in 49% of delay-tuned units in PP. The cortical representation of echo delay (chronotopy) covers a larger area in CP but is less precise than described in PP. Since chronotopy is absent in certain other insectivorous bat species, it is open if these differences in topography are related to echolocation behaviour.

Chronotopically Organized Target-Distance Map in the Auditory Cortex of the Short-Tailed Fruit Bat

Topographic cortical representation of echo delay, the cue for target range, is an organizational feature implemented in the auditory cortices of certain bats dedicated to catch flying insects. Such cortical echo-delay maps provide a calibrated neural representation of object spatial distance. To assess general requirements for echo-delay computations, cortical delay sensitivity was examined in the short-tailed fruit bat Carollia perspicillata that uses frequency-modulated (FM) echolocation signals. Delay-tuned neurons with temporal specificity comparable to those of insectivorous bats are located within the high-frequency (HF) field of the auditory cortex. All recorded neurons in the HF field respond well to single pure-tone and FM-FM stimulus pairs. The neurons respond to identical FM harmonic components in echolocation pulse and delayed echo (e.g., FM(2)-FM(2)). Their characteristic delays (CDs) for low echo amplitudes range between 1 and 24 ms, which is comparable to other bat species. Maps of the topography of FM-FM neurons show that they are distributed across the entire HF area and organized along a rostrocaudal echo-delay axis representing object distance. Rostrally located neurons tuned to delays of 2-8 ms are overrepresented (66% of CDs). Neurons with longer delays (>/=10 ms) are located throughout the caudal half of the HF field. The delay-sensitive chronotopic area covers approximately 3.3 mm in rostrocaudal and approximately 3.7 mm in dorsoventral direction, which is comparable or slightly larger than the size of cortical delay-tuned areas in insectivorous constant frequency bats, the only other bat species for which cortical chronotopy has been demonstrated. This indicates that chronotopic cortical organization is not only used exclusively for precise insect localization in constant frequency bats but could also be of advantage for general orientation tasks.

Bilateral Cortical Interaction: Modulation of Delay-Tuned Neurons in the Contralateral Auditory Cortex

Transcallosal excitation and inhibition have been theorized based on the effect of callosotomy on intractable epilepsy and dichotic listening research, respectively. We studied bilateral interaction of cortical auditory neurons and found that this interaction consisted of focused facilitation and widespread lateral inhibition. The frequency modulated (FM)-FM area of the auditory cortex of the mustached bat is composed of delay-tuned neurons tuned to the combination of the emitted biosonar pulse and its echo with a specific echo delay [best delay (BD)] and consists of three subdivisions in terms of the combination sensitivity of neurons. We found that focal electric stimulation of one of these three subdivisions evoked BD shifts of delay-tuned neurons in all three subdivisions of the contralateral FM-FM area, presumably via the corpus callosum. The effect of electric stimulation of the delay-tuned neurons on the contralateral delay-tuned neurons was different depending on whether the BD of a recorded neuron was matched or unmatched in BD with that of the stimulated neurons. BD-matched neurons did not change their BDs and increased the responses at their BDs, whereas BD-unmatched neurons shifted their BDs away from the BD of the stimulated neurons and reduced their responses. The ipsilateral and contralateral BD shifts evoked by the electric stimulation were identical to each other. The contralateral modulation, in addition to the ipsilateral modulation, increases the contrast in the neural representation of the echo delay to which the stimulated neurons are tuned.

Topographical distribution of delay-tuned responses in the mustached bat inferior colliculus

In the mustached bat, delay-tuned neurons respond best to specific delays between the first harmonic frequency modulated (FM) component (FM1; 24–29 kHz) of the emitted biosonar pulse and a higher harmonic FM component in returning echoes (e.g. FM3, 72–89 kHz). These delay-tuned, combinatorial responses predominate in the inferior colliculus (IC) of the mustached bat. This study examined the topographical distribution of delay-tuned neurons in the 72–89 kHz frequency representation of the IC. We recorded and histologically localized 163 single units. Ninety units were facilitated and 41 were inhibited by the combination of two frequencies in the 24–29 kHz and 72–89 kHz ranges. The facilitatory responses were selective for delays up to 20 ms between the two signals. To determine if delay-tuned neurons were topographically organized, we plotted the dorsomedio–ventrolateral and caudo–rostral positions of each unit versus its best delay. Best delay was not correlated with either location. Response latency to best frequency tones was topographically organized, but was not correlated with best delay. This indicates that the latency axis in the IC is unrelated to the delay tuning of these combinatorial neurons. Because delay-tuned neurons are not topographically organized in the IC but are in the auditory cortex, our findings suggest that the creation and organization of delay-tuned neurons occur at different stages in the ascending auditory system.

Delay-tuned neurons in the inferior colliculus of the mustached bat: implications for analyses of target distance.

We examined response properties of delay-tuned neurons in the central nucleus of the inferior colliculus (ICC) of the mustached bat. In the mustached bat, delay-tuned neurons respond best to the combination of the first-harmonic, frequency-modulated (FM1) sweep in the emitted pulse and a higher harmonic frequency-modulated (FM2, FM3 or FM4) component in returning echoes and are referred to as FM-FM neurons. We also examined H1-CF2 neurons. H1-CF2 neurons responded to simultaneous presentation of the first harmonic (H1) in the emitted pulse and the second constant frequency (CF2) component in returning echoes. These neurons served as a comparison as they are thought to encode different features of sonar targets than FM-FM neurons. Only 7% of our neurons (14/198) displayed a single excitatory tuning curve. The rest of the neurons (184) displayed complex responses to sounds in two separate frequency bands. The majority (51%, 101) of neurons were facilitated by the combination of specific components in the mustached bat's vocalizations. Twenty-five percent showed purely inhibitory interactions. The remaining neurons responded to two separate frequencies, without any facilitation or inhibition. FM-FM neurons (69) were facilitated by the FM1 component in the simulated pulse and a higher harmonic FM component in simulated echoes, provided the high-frequency signal was delayed the appropriate amount. The delay producing maximal facilitation ("best delay") among FM-FM neurons ranged between 0 and 20 ms, corresponding to target distances </=3.4 m. Sharpness of delay tuning varied among FM-FM neurons with 50% delay widths between 2 and 13 ms. On average, the facilitated responses of FM-FM neurons were 104% greater than the sum of the responses to the two signals alone. In comparing response properties of delay-tuned, FM-FM neurons in the ICC with those in the medial geniculate body (MGB) from other studies, we find that the range of best delays, sharpness of delay tuning and strength of facilitation are similar in the ICC and MGB. This suggests that by the level of the IC, the basic response properties of FM-FM neurons are established, and they do not undergo extensive transformations with ascending auditory processing.

NMDA-mediated facilitation in the echo-delay tuned areas of the auditory cortex of the mustached bat

We recorded the responses of single delay-tuned neurons in the dorsal fringe (DF) area and the FM–FM area of the auditory cortex of the mustached bat using multi-barreled carbon-fiber electrodes. An iontophoretic application of N-methyl- d-aspartate (NMDA) or kainate (KA) to a DF neuron evoked a burst of discharges from the neuron. The burst of discharges evoked by NMDA was always smaller than that evoked by KA. Simultaneous application of d-2-Amino-5-phosphonovalerate (APV) with NMDA and KA abolished the NMDA-evoked but not the KA-evoked discharges. APV did not evoke any significant changes in the auditory responses of 43 out of the 47 delay-tuned neurons studied in the DF area, and in all 20 neurons studied in the FM–FM area. In the remaining four DF neurons, however, APV either increased the initial discharges of their auditory response or decreased the late discharges of their response. These results indicate that in the majority of neurons in the DF and FM–FM areas NMDA receptors do not play a significant role in the processing of target-distance information, and that their facilitative auditory responses are basically created by synaptic interactions occurring in the subcortical auditory nuclei.

Corticofugal Modulation of Time-Domain Processing of Biosonar Information in Bats

The Jamaican mustached bat has delay-tuned neurons in the inferior colliculus, medial geniculate body, and auditory cortex. The responses of these neurons to an echo are facilitated by a biosonar pulse emitted by the bat when the echo returns with a particular delay from a target located at a particular distance. Electrical stimulation of cortical delay-tuned neurons increases the delay-tuned responses of collicular neurons tuned to the same echo delay as the cortical neurons and decreases those of collicular neurons tuned to different echo delays. Cortical neurons improve information processing in the inferior colliculus by way of the corticocollicular projection.

Long delay lines for ranging are created by inhibition in the inferior colliculus of the mustached bat.

1. The central auditory system of the mustached bat has arrays of delay-tuned (FM-FM combination-sensitive) neurons in the inferior colliculus, the medial geniculate body, and the auditory cortex. These neurons are tuned to particular echo delays, i.e., target distances. The neural mechanisms for creating the delay-tuned neurons involve delay lines, coincidence detection, and amplification. We have hypothesized that delay lines longer than 4 ms are created by inhibition occurring in the anterolateral division (ALD) of the central nucleus of the inferior colliculus. If this hypothesis is correct, suppression of inhibition occurring in the ALD must shorten the best delays of the collicular, thalamic, and cortical delay-tuned neurons. The aim of the present study is to test this hypothesis. Responses of single delay-tuned neurons in the FM-FM area of the auditory cortex were recorded with a tungsten-wire microelectrode, and the effects of iontophoretic microinjections of strychnine (STR) and/or bicuculline methiodide (BMI) into the ALD were examined on the responses of these neurons. 2. STR (glycine receptor antagonist) and/or BMI [gamma-aminobutyric acid-A (GABAA) receptor antagonist] injections into the ALD shortened the best delays of delay-tuned neurons in the FM-FM area with little change in their response patterns. The longer the best delay of a delay-tuned neuron, the larger the amount of shortening. 3. Inhibition mediated by glycine receptors plays a larger role in creating delay lines than that mediated by GABAA receptors, because STR and BMI, respectively, shortened the best delay of 91 and 74% of the neurons with best delays longer than 4.5 ms. 4. BMI has no effect on the best delays of delay-tuned neurons that were tuned to echo delays shorter than 4.5 ms. 5. The present data support the hypothesis that long delay lines utilized by delay-tuned neurons are created by inhibition occurring in the ALD of the inferior colliculus. However, the amount of shortening in delay lines by STR and/or BMI was generally smaller than that predicted by a neural network model. Therefore the present study partially answers the questions of where and how long delay lines were created.