Excitatory Frequency Tuning Curves Research Articles

Response properties underlying selectivity for the rate of frequency modulated sweeps in the auditory cortex of the mouse

This study focused on the response properties underlying selectivity for the rate of frequency modulated (FM) sweeps in the auditory cortex of anesthetized C57bl/6 (C57) mice. Linear downward FM sweeps with rates between 0.08 and 20 kHz/ms were tested. We show that at least two different response properties predict FM rate selectivity: sideband inhibition and duration tuning. Sideband inhibition was determined using the two-tone inhibition paradigm in which excitatory and inhibitory tones were presented with different delays. Sideband inhibition was present in the majority (88%, n = 53) of neurons. The spectrotemporal properties of sideband inhibition predicted rate selectivity and exclusion of the sideband from the sweep reduced/eliminated rate tuning. The second property predictive of sweep rate selectivity was duration tuning for tones. Theoretically, if a neuron is selective for the duration that a sweep spends in the excitatory frequency tuning curve, then rate selectivity will ensue. Duration tuning for excitatory tones was present and predicted rate selectivity in ∼34% of neurons (n = 97). Both sideband inhibition and duration tuning predicted rate selectivity equally well, but sideband inhibition was present in a larger percentage of neurons suggesting that it is the dominant mechanism in the C57 mouse auditory cortex. Similar mechanisms shape sweep rate selectivity in the auditory system of bats and mice and movement-velocity selectivity in the visual system, suggesting similar solutions to analogous problems across sensory systems. This study provides baseline data on basic spectrotemporal processing in the C57 strain for elucidation of changes that occur in presbycusis.

Inhibition shapes selectivity to vocalizations in the inferior colliculus of awake mice.

The inferior colliculus (IC) is a major center for integration of auditory information as it receives ascending projections from a variety of brainstem nuclei as well as descending projections from the thalamus and auditory cortex. The ascending projections are both excitatory and inhibitory and their convergence at the IC results in a microcircuitry that is important for shaping responses to simple, binaural, and modulated sounds in the IC. Here, we examined the role inhibition plays in shaping selectivity to vocalizations in the IC of awake, normal-hearing adult mice (CBA/CaJ strain). Neurons in the IC of mice show selectivity in their responses to vocalizations, and we hypothesized that this selectivity is created by inhibitory microcircuitry in the IC. We compared single unit responses in the IC to pure tones and a variety of ultrasonic mouse vocalizations before and after iontophoretic application of GABAA receptor (GABAAR) and glycine receptor (GlyR) antagonists. The most pronounced effects of blocking GABAAR and GlyR on IC neurons were to increase spike rates and broaden excitatory frequency tuning curves in response to pure tone stimuli, and to decrease selectivity to vocalizations. Thus, inhibition plays an important role in creating selectivity to vocalizations in the IC.

Spatial organization of receptive fields in the auditory midbrain of awake mouse

Efficient encoding of sensory information can be implemented by heterogeneous response properties of neurons within sensory pathways. In the auditory system, neurons in the main auditory midbrain nucleus, the inferior colliculus (IC), show heterogeneous response properties to various types of acoustic stimuli including behaviorally relevant sounds. The receptive fields of these neurons, and their spatial organization, may reveal mechanisms that underlie response heterogeneity in the IC. The mouse is becoming an increasingly popular system for auditory studies and although some studies have examined spectral characteristics in the IC, most of these have been conducted in anesthetized animals. There were two goals of this study. The first goal was to examine the frequency representation of awake mouse IC in fine spatial resolution. The second goal was to determine whether there is a spatial organization of excitatory frequency tuning curves in the IC of awake mice. We achieved these goals by histologically reconstructing locations of single and multiunit recordings throughout the IC in a mouse strain with normal hearing (CBA/CaJ). We found that the tonotopic progression is discontinuous in mouse IC, and we found that there is no clear spatial organization of frequency tuning curve types. Rather, there is heterogeneity of receptive fields in the bulk of the IC such that frequency tuning characteristics and hence the structure of excitatory and inhibitory inputs does not depend on location in the IC. This heterogeneity likely provides a mechanism for efficient encoding of auditory stimuli throughout the extent of the mouse IC.

Over-representation of species-specific vocalizations in the awake mouse inferior colliculus

Social vocalizations are particularly important stimuli in an animal's auditory environment. Because of their importance, vocalizations should be strongly represented in auditory pathways. Mice commonly emit ultrasonic vocalizations with spectral content between 45 and 100 kHz. However, there is limited representation of these ultra-high frequencies (particularly those greater than 60 kHz) throughout the ascending auditory system. Here, we show that neurons in the inferior colliculus (IC) of mice respond strongly to conspecific vocalizations even though the energy in the vocalizations is above the neurons' frequency tuning curves. This results in an over-representation of species-specific vocalizations in the IC. In addition, neurons in mouse IC show selectivity among different vocalizations. Many vocalization-responsive neurons do not respond to the individual ultrasonic frequencies contained within the vocalizations, but they do respond to combinations of ultrasonic tones if the difference between the tones is within the excitatory frequency tuning curve. The combinations of tones that elicit responses are the quadratic and/or cubic intermodulation distortion components that are generated by the cochlea. Thus, the intermodulation distortions in the cochlea may provide a previously overlooked mechanism for auditory processing of complex stimuli such as vocalizations. The implication of these findings is that nonlinear interactions of frequencies, possibly caused by distortions in the system, may be used to enhance the sensitivity to behaviorally important stimuli.

Binaural interaction in the inferior colliculus of the big brown bat, Eptesicus fuscus

Binaural interaction plays an important role in shaping response properties of central auditory neurons. Using single unit recording and iontophoresis, we examined frequency tuning curves (FTCs), interaural intensity difference (IID) curves, and rate–intensity functions of inferior collicular (IC) neurons of the big brown bat, Eptesicus fuscus, under closed system or free field stimulation conditions. We isolated 46 EI (excitation–inhibition), 24 EO (monaural excitation) and 6 EE (excitation–excitation) neurons. Inhibitory FTCs of EI neurons plotted under ipsilateral sound stimulation fell within ( n=10, 22%), partly overlapped ( n=26, 56%), or almost entirely encompassed ( n=10, 22%) excitatory FTCs plotted by contralateral sound stimulation. The discharge rate of EI neurons was a sigmoid function of IID. The peak discharge rate occurred at IIDs at which contralateral sound stimulation was stronger than ipsilateral sound stimulation. Application of bicuculline, an antagonist for γ-aminobutyric acid A receptors, raised the IID curves and broadened the excitatory FTCs but partly or completely abolished the ipsilateral inhibitory FTCs. For EE neurons, excitatory FTCs and rate–intensity functions plotted by contralateral sound stimulation were always broader and higher than those plotted by ipsilateral sound stimulation. The sharpness of FTCs of EI neurons was significantly greater at ipsilateral 30° than at 30° contralateral. This direction-dependent frequency tuning was effectively abolished by occlusion of the ipsilateral ear. Possible mechanisms underlying these observations are discussed.

The effect of two-tone stimulation on responses of two simultaneously recorded neurons in the inferior colliculus of the big brown bat, Eptesicus fuscus

This study examined auditory responses of two simultaneously recorded neurons in the central nucleus of bat inferior colliculus (IC) under two-tone stimulation conditions. We specifically examined how a sound within the excitatory frequency tuning curve (FTC) of one IC neuron might affect responses of the other IC neuron in amplitude and frequency domains. Under this specific two-tone stimulation condition, responses of 82% neurons were suppressed and their excitatory FTCs sharpened. Responses of the other 18% neurons were facilitated and their excitatory FTCs broadened. Two-tone suppression was greater at low than at high stimulus amplitudes. Two-tone suppression also decreased with increasing recording depth and best frequency (BF) difference between each pair of neurons. The suppressive or facilitatory FTC of a neuron plotted under two-tone stimulation conditions was always within the excitatory FTC of the other neuron. Two-tone suppression or two-tone facilitation was weak near the BF but became increasingly strong with frequencies away from the BF. Biological significance of these findings is discussed.

Interaction of excitation and inhibition in inferior collicular neurons of the big brown bat, Eptesicus fuscus

Neurons in the inferior colliculus (IC) of the midbrain receive convergent excitatory and inhibitory inputs from both lower and higher auditory nuclei. Interaction of these two opposing inputs shapes different response properties of IC neurons. In this study, we examined this interaction of excitation and inhibition in IC neurons using a probe (excitatory pulse) and a masker (inhibitory pulse) under different stimulation conditions. Inhibition of probe-elicited responses by a masker, i.e. masking, occurred when the masker was presented at certain inter-pulse intervals (the temporal window) in relation to the probe. At the best inter-pulse interval, masking was maximal such that a neuron had the minimal number of impulses, the longest response latency, and the smallest excitatory frequency tuning curve. The temporal window for masking expanded with increasing masker duration. The inhibition decreased with increasing probe intensity but increased with increasing masker intensity. Increasing masker intensity also produced progressive shrinkage in excitatory frequency tuning curves. Similarly, increasing probe intensity produced progressive shrinkage of inhibitory frequency tuning curves. Possible mechanisms underlying the time and intensity dependence of inhibition are discussed.

GABAergic and glycinergic neural inhibition in excitatory frequency tuning of bat inferior collicular neurons.

This study examined the effect of GABAergic and glycinergic inhibition on excitatory frequency tuning curves (FTCs) of inferior collicular (IC) neurons of the big brown bat, Eptesicus fuscus. The excitatory FTCs of 70 IC neurons were either V-shaped (57, 81%), closed (11, 16%), or double-peaked (2, 3%). By means of a two-tone stimulation paradigm, inhibitory FTCs were obtained at one frequency flank only (low-frequency flank: 11, 16%; high-frequency flank: 7, 10%), at both frequency flanks (36, 51%) of excitatory FTCs, or between two excitatory FTCs (2, 3%). IC neurons that had inhibitory FTCs typically had larger Q(10) and Q(30) values (i.e., sharper excitatory FTCs) than neurons that did not have inhibitory FTCs. Neurons with inhibitory FTCs at both frequency flanks had larger Q(10) and Q(30) values than neurons with inhibitory FTCs at one frequency flank only. IC neurons with a small difference between excitatory and inhibitory best frequencies typically had sharper excitatory frequency tuning. Bicuculline (an antagonist for GABAA) application produced a greater degree of abolishing inhibitory FTCs than strychnine (an antagonist for glycine) application. Application of both drugs was most effective in abolishing the inhibitory FTCs of IC neurons. The implications of these findings for bat echolocation are discussed.

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.

Auditory cortical neuron response differences under isoflurane versus pentobarbital anesthesia

Response properties of the middle layers of feline primary auditory cortex neurons to simple sounds were compared for isoflurane versus pentobarbital anesthesia in a within subject study control design. Initial microelectrode recordings were made under isoflurane anesthesia. After a several hour washout period, recordings were repeated at spatially matched locations in the same animal under pentobarbital. The median spatial separation between matched recording locations was 50 microns. Excitatory frequency tuning curves ( n=71 pairs) to tone bursts and entrainment to click train sequences ( n=64 pairs) ranging from 2 to 38 Hz were measured. Characteristic frequency and BW10 and BW30 were not different under either anesthetic. The spontaneous rate was slightly decreased ( P<0.05) for isoflurane (median 4.2 spikes/s) compared to pentobarbital (median 5.8 spikes/s). Minimum median threshold and latency were elevated by 12 dB and 2 ms, respectively, under isoflurane. Entrainment to click sequences assumed a lowpass filter profile under both anesthetics, but was markedly impoverished under isoflurane. Responses to click sequences under isoflurane were phasic to the first click but had very poor following to subsequent elements. Compared to pentobarbital, isoflurane appears to have a profound impact on response sensitivity and temporal response properties of auditory cortical neurons.

Corticofugal modulation of frequency tuning of inferior collicular neurons in big brown bat,Eptesicus fuscus

In order to explore the possible mechanism of corticofugal modulation of excitatory frequency tuning curves (EFTCs) of midbrain neurons, we examined the change of sharpness, frequency-intensity response area, minimum threshold of both EFTCs and inhibitory frequency tuning curves (IFTCs) of inferior collicular neurons during corticofugal modulation using two-tone inhibition paradigm and micro-electrical stimulation technique. Our data showed that corticofugal inhibition increased sharpness, minimum threshold, and decreased the frequency-intensity response area of EFTCs, at the same time it decreased the sharpness, minimum threshold but increased the frequency-intensity response area of IFTCs. The opposite results were observed for EFTCs and IFTCs of corticofugally facilitated inferior collicular neurons. During corticofugal inhibition, the percent change of frequency-intensity response area of EFTCs had significant correlation with the percent change of that of IFTCs. These data suggest that cortical neurons are likely to improve frequency information processing of inferior collicular neurons by modulation of IFTCs.