Combination-sensitive Neurons Research Articles

Specialization of Neurons with Different Response Patterns in the Mouse Mus musculus Auditory Midbrain and Primary Auditory Cortex during Communication Call Processing

Wriggling call produced by mouse pups when struggling in the nest is one of the mouse early ontogenesis communicative vocalization. Processing of these signals by auditory midbrain and primary auditory cortex neurons with different response patterns was the subject of this study. Responses of single neurons evoked by wriggling call models and a series of models consisting of 4 stimuli with different interstimulus intervals (0–1000 ms) were recorded extracellularly. A third of central nucleus neurons in the inferior colliculus showed a spectral facilitation in responses to various two- and three-tone combinations of the wriggling call frequency components. About 80% of such combination-sensitive neurons had tonic characteristics of responses, i.e. tonic, phasic-tonic, pauser and long-latency discharges. A study of responses of central nucleus neurons to a series of wriggling call models showed that at short interstimulus intervals (0–50 ms) responses to the 2nd–4th signals in a series were completely suppressed or significantly decreased in two-thirds of the recorded neurons, i.e. there arose adaptation to a series of sounds. Such neurons had mainly phasic discharges. In a third of neurons, adaptation did not arise; these neurons were tonically discharging. All neurons in the primary auditory cortex (anterior and primary auditory fields) demonstrated adaptation in responses to a series of wriggling calls. Discharges of neurons were phasic.

Inhibitory mechanisms shaping delay-tuned combination-sensitivity in the auditory cortex and thalamus of the mustached bat

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. The subcollicular nuclei produce latency-constant phasic on-responding neurons, and the inferior colliculus produces delay-tuned combination-sensitive neurons, designated “FM-FM” neurons. The combination-sensitivity is a facilitated response to the coincidence of the excitatory rebound following glycinergic inhibition to the pulse (1st harmonic) and the short-latency response to the echo (2nd–4th harmonics). The facilitative response of thalamic FM-FM neurons is mediated by glutamate receptors (NMDA and non-NMDA receptors). Different from collicular FM-FM neurons, thalamic ones respond more selectively to pulse-echo pairs than individual signal elements. A number of differences in response properties between collicular and thalamic or cortical FM-FM neurons have been reported. However, differences between thalamic and cortical FM-FM neurons have remained to be studied. Here, we report that GABAergic inhibition controls the duration of burst of spikes of facilitative responses of thalamic FM-FM neurons and sharpens the delay tuning of cortical ones. That is, intra-cortical inhibition sharpens the delay tuning of cortical FM-FM neurons that is potentially broad because of divergent/convergent thalamo-cortical projections. Compared with thalamic neurons, cortical ones tend to show sharper delay tuning, longer response duration, and larger facilitation index. However, those differences are statistically insignificant.

Nonlinear processing of a multicomponent communication signal by combination-sensitive neurons in the anuran inferior colliculus.

Diverse animals communicate using multicomponent signals. How a receiver's central nervous system integrates multiple signal components remains largely unknown. We investigated how female green treefrogs (Hyla cinerea) integrate the multiple spectral components present in male advertisement calls. Typical calls have a bimodal spectrum consisting of formant-like low-frequency (~0.9kHz) and high-frequency (~2.7kHz) components that are transduced by different sensory organs in the inner ear. In behavioral experiments, only bimodal calls reliably elicited phonotaxis in no-choice tests, and they were selectively chosen over unimodal calls in two-alternative choice tests. Single neurons in the inferior colliculus of awake, passively listening subjects were classified as combination-insensitive units (27.9%) or combination-sensitive units (72.1%) based on patterns of relative responses to the same bimodal and unimodal calls. Combination-insensitive units responded similarly to the bimodal call and one or both unimodal calls. In contrast, combination-sensitive units exhibited both linear responses (i.e., linear summation) and, more commonly, nonlinear responses (e.g., facilitation, compressive summation, or suppression) to the spectral combination in the bimodal call. These results are consistent with the hypothesis that nonlinearities play potentially critical roles in spectral integration and in the neural processing of multicomponent communication signals.

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.

Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum.

Social Calls Exhibit a Distributed Consensus Map in the Auditory Cortex of Mustached Bats

Social Calls Exhibit a Distributed Consensus Map in the Auditory Cortex of Mustached Bats

Neural Coding of Call Pitch and Syllable Type in the Auditory Cortex of Mustached Bats

Neural Coding of Call Pitch and Syllable Type in the Auditory Cortex of Mustached Bats

Circuitry Underlying Spectrotemporal Integration in the Auditory Midbrain

Combination sensitivity in central auditory neurons is a form of spectrotemporal integration in which excitatory responses to sounds at one frequency are facilitated by sounds within a distinctly different frequency band. Combination-sensitive neurons respond selectively to acoustic elements of sonar echoes or social vocalizations. In mustached bats, this response property originates in high-frequency representations of the inferior colliculus (IC) and depends on low and high frequency-tuned glycinergic inputs. To identify the source of these inputs, we combined glycine immunohistochemistry with retrograde tract tracing. Tracers were deposited at high-frequency (>56 kHz), combination-sensitive recording sites in IC. Most glycine-immunopositive, retrogradely labeled cells were in ipsilateral ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL), with some double labeling in ipsilateral lateral and medial superior olivary nuclei (LSO and MSO). Generally, double-labeled cells were in expected high-frequency tonotopic areas, but some VNLL and INLL labeling appeared to be in low-frequency representations. To test whether these nuclei provide low frequency-tuned input to the high-frequency IC, we combined retrograde tracing from IC combination-sensitive sites with anterograde tracing from low frequency-tuned sites in the anteroventral cochlear nucleus (AVCN). Only VNLL and INLL contained retrogradely labeled cells near (≤50 μm) anterogradely labeled boutons. These cells likely receive excitatory low-frequency input from AVCN. Results suggest that combination-sensitive facilitation arises through convergence of high-frequency glycinergic inputs from VNLL, INLL, or MSO and low-frequency glycinergic inputs from VNLL or INLL. This work establishes an anatomical basis for spectrotemporal integration in the auditory midbrain and a functional role for monaural nuclei of the lateral lemniscus.

Combination-sensitive neurons in the central nucleus of inferior colliculus of the house mouse Mus musculus

tion in this analysis. The goal of the present work was to reveal mechanisms of spectral processing of complex communicative signals by neurons of the central nucleus of inferior colliculus.This work evaluates extracellular activity of single neurons of the central nucleus of the house mouse inferior colliculus, evoked by call of dis-comfort from repertoire of early ontogeny of the mouse pups, so called “wriggling call,” its model reproducing harmonic structure of natural call and its frequency components. The wriggling call is a nest call of discomfort of mouse pups. It in-duces the instinctive maternal behavior—care of pups, building of nest, and a change of the mater-nal body position during lactation [7]. The main features of the call are its low frequency range (the main energy is concentrated between 2 and 15 kHz) and the pronounced harmonic structure (the call is formed by three major equally-powered harmonics located at 5, 10, and 15 kHz). Neu-ral responses to the wriggling call model, natural wriggling call, and its components were compared with organization of neuronal frequency receptive fields.The study was carried out on females of F1 hy-brids of CBA and C57BL/6 strains at the age of 8–15 weeks. Anesthesia was performed by intra-The most important function of the auditory system is processing of communicative acoustic signals. However, how analysis of communica-tive signals occurs in the brain auditory centers re-mains to be elucidated and, moreover, we do not know what principles underlie the communicative signal discrimination by the auditory system from the diversity of complex sounds. Studies of neuro-nal mechanisms of the analysis of species-specific signals were carried out predominantly in the fore-brain auditory centers of the acoustically special-ized objects [1–3]. At the same time, numerous ascending, descending, and commissural connec-tions of neurons of the midbrain auditory center, the inferior colliculus, structural orderliness of its central nucleus, location of information about var-ious features of auditory signals, high variability of neuronal response patterns allow suggesting that this structure has necessary prerequisites for en-coding of communicative signals [4]. However, so far, there are only occasional works showing selec-tivity of neuronal responses in the central nucleus of the bat inferior colliculus to species-specific signals [5, 6], while neurophysiologic mechanisms of analysis of communicative signals at the level of midbrain auditory neurons remain practically not studied. Much less studied is neuronal specializa-

Auditory Cortex: Representation through Sparsification?

The recent discovery of combination-sensitive neurons in the primary auditory cortex of awake marmosets may reconcile previous, apparently contradictory, findings that cortical neurons produce strong, sustained responses, but also represent stimuli sparsely.

Intracellular Recordings From Combination-Sensitive Neurons in the Inferior Colliculus

In vertebrate auditory systems, specialized combination-sensitive neurons analyze complex vocal signals by integrating information across multiple frequency bands. We studied combination-sensitive interactions in neurons of the inferior colliculus (IC) of awake mustached bats, using intracellular somatic recording with sharp electrodes. Facilitated combinatorial neurons are coincidence detectors, showing maximum facilitation when excitation from low- and high-frequency stimuli coincide. Previous work showed that facilitatory interactions originate in the IC, require both low and high frequency-tuned glycinergic inputs, and are independent of glutamatergic inputs. These results suggest that glycinergic inputs evoke facilitation through either postinhibitory rebound or direct depolarizing mechanisms. However, in 35 of 36 facilitated neurons, we observed no evidence of low frequency-evoked transient hyperpolarization or depolarization that was closely related to response facilitation. Furthermore, we observed no evidence of shunting inhibition that might conceal inhibitory inputs. Since these facilitatory interactions originate in IC neurons, the results suggest that inputs underlying facilitation are electrically segregated from the soma. We also recorded inhibitory combinatorial interactions, in which low frequency sounds suppress responses to higher frequency signals. In 43% of 118 neurons, we observed low frequency-evoked hyperpolarizations associated with combinatorial inhibition. For these neurons, we conclude that low frequency-tuned inhibitory inputs terminate on neurons primarily excited by high-frequency signals; these inhibitory inputs may create or enhance inhibitory combinatorial interactions. In the remainder of inhibited combinatorial neurons (57%), we observed no evidence of low frequency-evoked hyperpolarizations, consistent with observations that inhibitory combinatorial responses may originate in lateral lemniscal nuclei.

Glycinergic “Inhibition” Mediates Selective Excitatory Responses to Combinations of Sounds

In the mustached bat's inferior colliculus (IC), combination-sensitive neurons display time-sensitive facilitatory interactions between inputs tuned to distinct spectral elements in sonar or social vocalizations. Here we compare roles of ionotropic receptors to glutamate (iGluRs), glycine (GlyRs), and GABA (GABA(A)Rs) in facilitatory combination-sensitive interactions. Facilitatory responses to 36 single IC neurons were recorded before, during, and after local application of antagonists to these receptors. The NMDA receptor antagonist CPP [(+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid], alone (n = 14) or combined with AMPA receptor antagonist NBQX (n = 22), significantly reduced or eliminated responses to best frequency (BF) sounds across a broad range of sound levels, but did not eliminate combination-sensitive facilitation. In a subset of neurons, GABA(A)R blockers bicuculline or gabazine were applied in addition to iGluR blockers. GABA(A)R blockers did not "uncover" residual iGluR-mediated excitation, and only rarely eliminated facilitation. In nearly all neurons for which the GlyR antagonist strychnine was applied in addition to iGluR blockade (22 of 23 neurons, with or without GABA(A)R blockade), facilitatory interactions were eliminated. Thus, neither glutamate nor GABA neurotransmission are required for facilitatory combination-sensitive interactions in IC. Instead, facilitation may depend entirely on glycinergic inputs that are presumed to be inhibitory. We propose that glycinergic inputs tuned to two distinct spectral elements in vocal signals each activate postinhibitory rebound excitation. When rebound excitations from two spectral elements coincide, the neuron discharges. Excitation from glutamatergic inputs, tuned to the BF of the neuron, is superimposed onto this facilitatory interaction, presumably mediating responses to a broader range of acoustic signals.

Roles of Inhibition in Complex Auditory Responses in the Inferior Colliculus: Inhibited Combination-Sensitive Neurons

We studied the functional properties and underlying neural mechanisms associated with inhibitory combination-sensitive neurons in the mustached bat's inferior colliculus (IC). In these neurons, the excitatory response to best frequency tones was suppressed by lower frequency signals (usually in the range of 12-30 kHz) in a time-dependant manner. Of 143 inhibitory units, the majority (71%) were type I, in which low-frequency sounds evoked inhibition only. In the remainder, however, the low-frequency inhibitory signal also evoked excitation. Of these, excitation preceded the inhibition in type E/I units (16%), whereas in type I/E units (13%), excitation followed the inhibition. Type E/I and I/E units were distinct in the tuning and threshold sensitivity of low-frequency responses, whereas type I units overlapped the other types in these features. In 71 neurons, antagonists to receptors for glycine [strychnine (STRY)] or GABA [bicuculline (BIC)] were applied microiontophoretically. These antagonists failed to eliminate combination-sensitive inhibition in 92% (STRY), 93% (BIC), and 87% (BIC + STRY) of the type I units tested. However, inhibition was reduced in many neurons. Results were similar for type E/I and I/E inhibitory neurons. The results indicate that there are distinct populations of combination-sensitive inhibited neurons in the IC and that these populations are at least partly independent of glycine or GABAA receptors in the IC. We propose that these populations originate in different brain stem auditory nuclei, that they may be modified by interactions within the IC, and that they may perform different spectrotemporal analyses of vocal signals.

Roles of Inhibition in Creating Complex Auditory Responses in the Inferior Colliculus: Facilitated Combination-Sensitive Neurons

We studied roles of inhibition on temporally sensitive facilitation in combination-sensitive neurons from the mustached bat's inferior colliculus (IC). In these integrative neurons, excitatory responses to best frequency (BF) tones are enhanced by much lower frequency signals presented in a specific temporal relationship. Most facilitated neurons (76%) showed inhibition at delays earlier than or later than the delays causing facilitation. The timing of inhibition at earlier delays was closely related to the best delay of facilitation, but the inhibition had little influence on the duration or strength of the facilitatory interaction. Local iontophoretic application of antagonists to receptors for glycine (strychnine, STRY) and gamma-aminobutyric acid (GABA) (bicuculline, BIC) showed that STRY abolished facilitation in 96% of tested units, but BIC eliminated facilitation in only 28%. This suggests that facilitatory interactions are created in IC and reveals a differential role for these neurotransmitters. The facilitation may be created by coincidence of a postinhibitory rebound excitation activated by the low-frequency signal with the BF-evoked excitation. Unlike facilitation, inhibition at earlier delays was not eliminated by application of antagonists, suggesting an origin in lower brain stem nuclei. However, inhibition at delays later than facilitation, like facilitation itself, appears to originate within IC and to be more dependent on glycinergic than GABAergic mechanisms. Facilitatory and inhibitory interactions displayed by these combination-sensitive neurons encode information within sonar echoes and social vocalizations. The results indicate that these complex response properties arise through a series of neural interactions in the auditory brain stem and midbrain.

Spectral integration in the inferior colliculus of the CBA/CaJ mouse

The inferior colliculus receives a massive convergence of inputs and in the mustached bat, this convergence leads to the creation of neurons in the inferior colliculus that integrate information across multiple frequency bands. These neurons are tuned to multiple frequency bands or are combination-sensitive; responding best to the combination of two signals of different frequency composition. The importance of combination-sensitive neurons in processing echolocation signals is well described, and it has been thought that combination sensitivity is a neural specialization for echolocation behaviors. Combination sensitivity and other response properties indicative of spectral integration have not been thoroughly examined in the inferior colliculus of non-echolocating mammals. In this study we tested the hypothesis that integration across frequencies occurs in the inferior colliculus of mice. We tested excitatory frequency response areas in the inferior colliculus of unanesthetized mice by varying the frequency of a single tone between 6 and 100 kHz. We then tested combination-sensitive responses by holding one tone at the unit’s best frequency, and varying the frequency and intensity of a second tone. Thirty-two percent of the neurons were tuned to multiple frequency bands, 16% showed combination-sensitive facilitation and another 12% showed combination-sensitive inhibition. These findings suggests that the neural mechanisms underlying processing of complex sounds in the inferior colliculus share some common features among mammals as different as the bat and the mouse.

Evolutionary aspects of bat echolocation.

This review is yet another attempt to explain how echolocation in bats or bat-like mammals came into existence. Attention is focused on neuronal specializations in the ascending auditory pathway of echolocating bats. Three different mechanisms are considered that may create a specific auditory sensitivity to echos: (1). time-windows of enhanced echo-processing opened by a corollary discharge of neuronal vocalization commands; (2). differentiation and expansion of ensembles of combination-sensitive neurons in the midbrain; and (3). corticofugal top-down modulations. The second part of the review interprets three different types of echolocation as adaptations to ecological niches, and presents the sophisticated cochlear specializations in constant-frequency/frequency-modulated bats as a case study of finely tuned differentiation. It is briefly discussed how a resonant mechanism in the inner ear of constant-frequency/frequency-modulated bats may have evolved in common mammalian cochlea.

Signal Processing Systems for Echolocation in the Bat's Brain

The neural base of the bat's biosonar system is discussed here. The bat emits complex biosonar sounds (pulses) and listens to echoes for orientation and hunting flying insects. Different types of biosonar information are carried by different parameters characterizing pulse-echo pairs. For example, distance information is conveyed by echo delay, while velocity information is carried by Doppler shift. In the auditory cortex of the bat, not only frequency but also other information baring parameters such as echo delay and Doppler shift are systematically mapped as subareas. These computational maps greatly depend on subcortical signal processing. The subcortical auditory nuclei create delay lines and multipliers (or AND gates) for processing distance (echo delay) information, and also create level-tolerant frequency tuning and multipliers (or AND gates) for processing velocity (Doppler shift) information. These multipliers are called FM-FM and CF/CF combination sensitive neurons, respectively. The neurophysiological investigations of the bat's biosonar system provide an excellent database for neural computational models and sonar systems. Application of an agonist of inhibitory neurotransmitter to DSCF or FM-FM area behaviorally revealed the functions of these auditory subareas. Findings made by an on-board telemetry microphone from flying bats confirmed Doppler-shift compensation.

Modeling complex tone perception: grouping harmonics with combination-sensitive neurons.

Perception of complex communication sounds is a major function of the auditory system. To create a coherent precept of these sounds the auditory system may instantaneously group or bind multiple harmonics within complex sounds. This perception strategy simplifies further processing of complex sounds and facilitates their meaningful integration with other sensory inputs. Based on experimental data and a realistic model, we propose that associative learning of combinations of harmonic frequencies and nonlinear facilitation of responses to those combinations, also referred to as "combination-sensitivity," are important for spectral grouping. For our model, we simulated combination sensitivity using Hebbian and associative types of synaptic plasticity in auditory neurons. We also provided a parallel tonotopic input that converges and diverges within the network. Neurons in higher-order layers of the network exhibited an emergent property of multifrequency tuning that is consistent with experimental findings. Furthermore, this network had the capacity to "recognize" the pitch or fundamental frequency of a harmonic tone complex even when the fundamental frequency itself was missing.

Responses to combinations of tones in the nuclei of the lateral lemniscus.

Combination-sensitive neurons integrate specific spectral and temporal elements in biologically important sounds, and they may underlie the analysis of biosonar and social vocalizations. Combination-sensitive neurons are found in the forebrain of a variety of vertebrates. In the mustached bat, they also occur in the central nucleus of the inferior colliculus (ICC). However, it is not known where combination-sensitive response properties emerge. To address this question, we used a two-tone paradigm to examine responses of single units to combination stimuli in a brainstem structure, the nuclei of the lateral lemniscus (NLL). We recorded and histologically localized 101 single units in the NLL. The majority (82%) of units had a single excitatory frequency tuning curve. Seven units had two separate excitatory frequency tuning curves but displayed no combinatorial interaction. Twelve units were combination-sensitive. Of these, three units were facilitated by the combination of two separate frequency bands and nine units were inhibited by combinatorial stimuli. The three facilitatory neurons had excitatory responses tuned to the second harmonic constant frequency (CF2, 57-60 kHz) component of the biosonar signal and were facilitated by a second signal within the first harmonic (Hl, 24-30 kHz) of the biosonar call. Most of the inhibitory interactions occurred between signals in the frequency bands associated with the frequency-modulated (FM) components of the biosonar call. The strongest combinatorial effects (facilitatory and inhibitory) were elicited by simultaneous onset of the two signals (i.e., 0 ms delay). All combination-sensitive units were in the intermediate nucleus of the NLL (INLL), which in bats is a hypertrophied structure that projects strongly to combination-sensitive neurons in the ICC. Thus, the combination-sensitive neurons in the INLL may impart their response properties onto ICC neurons. However, the small number of facilitatory combination-sensitive neurons in the NLL suggests that the majority of these combinatorial responses originate in the ICC.

Spectral Integration in the Inferior Colliculus: Role of Glycinergic Inhibition in Response Facilitation

This study examined the contribution of glycinergic inhibition to the time-sensitive spectral integration performed by neurons in the inferior colliculus of the mustached bat (Pteronotus parnellii). These neurons are sometimes called combination-sensitive because they display facilitatory (or inhibitory) responses to the combination of distinct spectral elements in sonar or social vocalizations. Present in a wide range of vertebrates, their temporally and spectrally selective integration is thought to endow them with the ability to discriminate among social vocalizations or to analyze particular cues concerning sonar targets. The mechanisms that underlie these responses or the sites in the auditory system where they are created are not known. We examined combination-sensitive neurons that are facilitated by the presentation of two different harmonic elements of the bat's sonar call and echo. Responses of 24 single units were recorded before and during local application of strychnine, an antagonist of glycinergic inhibition. For each of the 24 units, strychnine application eliminated or greatly reduced temporally sensitive facilitation. There was no difference in this effect for neurons tuned to frequencies associated with the frequency-modulated or the constant-frequency sonar components. These results are unusual because glycine is considered to be an inhibitory neurotransmitter, but here it appears to be essential for the expression of combination-sensitive facilitation. The findings provide strong evidence that facilitatory combination-sensitive response properties present throughout the mustached bat's auditory midbrain, thalamus, and cortex originate through neural interactions in the inferior colliculus.