Frequency Modulated Rate Selectivity Research Articles

Network models of frequency modulated sweep detection.

Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The ‘facilitation’ model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The ‘duration tuned’ model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The ‘inhibitory sideband’ model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.

Altered cortical spectrotemporal processing with age-related hearing loss

Presbycusis (age-related hearing loss) is a prevalent disability associated with aging that impairs spectrotemporal processing, but the mechanisms of such changes remain unclear. The goal of this study was to quantify cortical responses to frequency-modulated (FM) sweeps in a mouse model of presbycusis. Previous studies showed that cortical neurons in young mice are selective for the rate of frequency change in FM sweeps. Here single-unit data on cortical selectivity and response variability to FM sweeps of either direction and different rates (0.08-20 kHz/ms) were compared across young (1-3 mo), middle-aged (6-8 mo), and old (14-20 mo) groups. Three main findings are reported. First, there is a reduction in FM rate selectivity in the old group. Second, there is a slowing of the sweep rates at which neurons likely provide best detection and discrimination of sweep rates. Third, there is an increase in trial-to-trial variability in the magnitude and timing of spikes in response to sweeps. These changes were only observed in neurons that were selective for the fast or intermediate range of sweep rates and not in neurons that preferred slow sweeps or were nonselective. Increased variability of response magnitude, but not changes in temporal fidelity or selectivity, was seen even in the middle-aged group. The results show that spectrotemporal processing becomes slow and noisy with presbycusis in specific types of neurons, suggesting receptive field mechanisms that are altered. These data suggest neural correlates of presbycusis-related reduction in the ability of humans to process rapid spectrotemporal changes.

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.

Development of response selectivity in the mouse auditory cortex

The mouse auditory system contains neurons selective for tone duration and for a narrow range of frequency modulated (FM) sweep rates. Whether such selectivity is developmentally regulated is not known. The main goal of this study was to follow the development of neuronal responses to tones (frequency and duration tuning) and FM sweeps (direction and rate selectivity) in the core auditory cortex (A1 and AAF) of ketamine/xylazine anesthetized C57bl/6 mice. Three groups were compared: postnatal day (P) 15–20, P21–30 and P31–90. Frequency tuning bandwidth decreased during the first month indicating refinement of the excitatory receptive field. Duration tuning for tones did not change during development in terms of categories of tuning types as well as measures of selectivity such as best duration and half-maximal duration. FM rate and direction selectivity were developmentally regulated. Selectivity for linear up and down FM sweeps (0.06–22 kHz/ms) was tested. The best rate and half-maximal rate of neurons categorized as fast- or band-pass selective shifted toward faster rates during development. The percentage of fast-pass selective neurons also increased during development. These data suggest that cortical neurons' discrimination and detection abilities for relatively faster sweep rates improve during development. Although on average, direction selectivity was weak across development, there was a significant shift toward upward sweep selectivity at slow rates. Thus, the C57bl/6 mouse auditory cortex is not adult-like until at least P30. The changes in response selectivity can be explained based on known developmental changes in intrinsic and synaptic properties of mouse auditory cortical neurons.

Mechanisms underlying intensity-dependent changes in cortical selectivity for frequency-modulated sweeps

Frequency-modulated (FM) sweeps are common components of species-specific vocalizations. The intensity of FM sweeps can cover a wide range in the natural environment, but whether intensity affects neural selectivity for FM sweeps is unclear. Bats, such as the pallid bat, which use FM sweeps for echolocation, are suited to address this issue, because the intensity of echoes will vary with target distance. In this study, FM sweep rate selectivity of pallid bat auditory cortex neurons was measured using downward sweeps at different intensities. Neurons became more selective for FM sweep rates present in the bat's echolocation calls as intensity increased. Increased selectivity resulted from stronger inhibition of responses to slower sweep rates. The timing and bandwidth of inhibition generated by frequencies on the high side of the excitatory tuning curve [sideband high-frequency inhibition (HFI)] shape rate selectivity in cortical neurons in the pallid bat. To determine whether intensity-dependent changes in FM rate selectivity were due to altered inhibition, the timing and bandwidth of HFI were quantified at multiple intensities using the two-tone inhibition paradigm. HFI arrived faster relative to excitation as sound intensity increased. The bandwidth of HFI also increased with intensity. The changes in HFI predicted intensity-dependent changes in FM rate selectivity. These data suggest that neural selectivity for a sweep parameter is not static but shifts with intensity due to changes in properties of sideband inhibition.

Multiple mechanisms shape FM sweep rate selectivity: complementary or redundant?

Auditory neurons in the inferior colliculus (IC) of the pallid bat have highly rate selective responses to downward frequency modulated (FM) sweeps attributable to the spectrotemporal pattern of their echolocation call (a brief FM pulse). Several mechanisms are known to shape FM rate selectivity within the pallid bat IC. Here we explore how two mechanisms, stimulus duration and high-frequency inhibition (HFI), can interact to shape FM rate selectivity within the same neuron. Results from extracellular recordings indicated that a derived duration-rate function (based on tonal response) was highly predictive of the shape of the FM rate response. Longpass duration selectivity for tones was predictive of slowpass rate selectivity for FM sweeps, both of which required long stimulus durations and remained intact following iontophoretic blockade of inhibitory input. Bandpass duration selectivity for tones, sensitive to only a narrow range of tone durations, was predictive of bandpass rate selectivity for FM sweeps. Conversion of the tone duration response from bandpass to longpass after blocking inhibition was coincident with a change in FM rate selectivity from bandpass to slowpass indicating an active inhibitory component to the formation of bandpass selectivity. Independent of the effect of duration tuning on FM rate selectivity, the presence of HFI acted as a fastpass FM rate filter by suppressing slow FM sweep rates. In cases where both mechanisms were present, both had to be eliminated, by removing inhibition, before bandpass FM rate selectivity was affected. It is unknown why the auditory system utilizes multiple mechanisms capable of shaping identical forms of FM rate selectivity though it may represent distinct but convergent modes of neural signaling directed at shaping response selectivity for important biologically relevant sounds.

Selectivity for the rate of frequency-modulated sweeps in the mouse auditory cortex

Frequency-modulated (FM) sweeps are common components of vocalizations, including human speech. Both sweep direction and rate influence discrimination of vocalizations. Across species, relatively less is known about FM rate selectivity compared with direction selectivity. In this study, FM rate selectivity was studied in the auditory cortex of anesthetized 1- to 3-mo-old C57bl/6 mice. Neurons were classified as fast pass, band pass, slow pass, or all pass depending on their selectivity for rates between 0.08 and 20 kHz/ms. Multiunit recordings were used to map FM rate selectivity at depths between 250 and 450 μm across both primary auditory cortex (A1) and the anterior auditory field (AAF). In terms of functional organization of rate selectivity, three patterns were found. First, in both A1 and AAF, neurons clustered according to rate selectivity. Second, most (∼60%) AAF neurons were either fast-pass or band-pass selective. Most A1 neurons (∼72%) were slow-pass selective. This distribution supports the hypothesis that AAF is specialized for faster temporal processing than A1. Single-unit recordings (n = 223) from A1 and AAF show that the mouse auditory cortex is best poised to detect and discriminate a narrow range of sweep rates between 0.5 and 3 kHz/ms. Third, based on recordings obtained at different depths, neurons in the infragranular layers were less rate selective than neurons in the granular layers, suggesting FM processing undergoes changes within the cortical column. On average, there was very little direction selectivity in the mouse auditory cortex. There was also no correlation between characteristic frequency and direction selectivity. The narrow range of rate selectivity in the mouse cortex indicates that FM rate processing is a useful physiological marker for studying contributions of genetic and environmental factors in auditory system development, aging, and disease.

Differential roles of GABAergic and glycinergic input on FM selectivity in the inferior colliculus of the pallid bat

Multiple mechanisms have been shown to shape frequency-modulated (FM) selectivity within the central nucleus of the inferior colliculus (IC) in the pallid bat. In this study we focus on the mechanisms associated with sideband inhibition. The relative arrival time of inhibition compared with excitation can be used to predict FM responses as measured with a two-tone inhibition paradigm. An early-arriving low-frequency inhibition (LFI) prevents responses to upward sweeps and thus shapes direction selectivity. A late-arriving high-frequency inhibition (HFI) suppresses slow FM sweeps and thus shapes rate selectivity for downward sweeps. Iontophoretic application of gabazine (GBZ) to block GABA(A) receptors or strychnine (Strych) to block glycine receptors was used to assess the effects of removal of inhibition on each form of FM selectivity. GBZ and Strych had a similar effect on FM direction selectivity, reducing selectivity in up to 86% of neurons when both drugs were coapplied. FM rate selectivity was more resistant to drug application with less than 38% of neurons affected. In addition, only Strych could eliminate FM rate selectivity, whereas GBZ alone was ineffective. The loss of FM selectivity was directly correlated to a loss of the respective inhibitory sideband that shapes that form of selectivity. The elimination of LFI correlated to a loss of FM direction selectivity, whereas elimination of HFI correlated to a loss of FM rate selectivity. Results indicate that 1) although the majority of FM direction selectivity is created within the IC, the majority of rate selectivity is inherited from lower levels of the auditory system, 2) a loss of LFI corresponds to a loss of FM direction selectivity and is created through either GABAergic or glycinergic input, and 3) a loss of HFI corresponds to a loss of FM rate selectivity and is created mainly through glycinergic input.

Experience-dependent development of vocalization selectivity in the auditory cortex

Vocalization-selective neurons are present in the auditory systems of several vertebrate groups. Vocalization selectivity is influenced by developmental experience, but the underlying mechanisms are only beginning to be understood. Evidence is presented in this review for the hypothesis that plasticity of timing and strength of inhibition is a mechanism for plasticity of vocalization selectivity. The pallid bat echolocates using downward frequency modulated (FM) sweeps. Nearly 70% of neurons with tuning in the echolocation frequency range in its auditory cortex respond selectively to the direction and rate of change of frequencies present in the echolocation call. During development, FM rate selectivity matures early, while direction selectivity emerges later. Based on the time course of development it was hypothesized that FM direction, but not rate, selectivity is experience-dependent. This hypothesis was tested by altering echolocation experience during development. The results show that normal echolocation experience is required for both refinement and maintenance of direction selectivity. Interestingly, experience is required for the maintenance of rate selectivity, but not for initial development. Across all ages and experimental groups, the timing relationship between inhibitory and excitatory inputs explains sweep selectivity. These experiments suggest that inhibitory plasticity is a substrate for experience-dependent changes in vocalization selectivity.

Experience is required for the maintenance and refinement of FM sweep selectivity in the developing auditory cortex

Frequency modulated (FM) sweeps are common components of vocalizations, including human speech. How developmental experience shapes neuronal selectivity for these important signals is not well understood. Here, we show that altered developmental experience with FM sweeps used in echolocation by the pallid bat leads to either a loss of sideband inhibition or millisecond delays in the timing of inhibitory inputs, both of which lead to a reduction in rate and direction selectivity in auditory cortex. FM rate selectivity develops in an experience-independent manner, but requires experience for subsequent maintenance. Direction selectivity depends on experience for both development and maintenance. Rate and direction selectivity are affected by experience over different time periods during development. Altered inhibition may be a general mechanism of experience-dependent plasticity of selectivity for vocalizations.

Development of Inhibitory Mechanisms Underlying Selectivity for the Rate and Direction of Frequency-Modulated Sweeps in the Auditory Cortex

Although it is known that neural selectivity for species-specific vocalizations changes during development, the mechanisms underlying such changes are not known. This study followed the development of mechanisms underlying selectivity for the direction and rate of frequency-modulated (FM) sweeps in the auditory cortex of the pallid bat, a species that uses downward FM sweeps to echolocate. In the adult cortex, direction and rate selectivity arise as a result of different spectral and temporal properties of low-frequency inhibition (LFI) and high-frequency inhibition (HFI). A narrow band of delayed HFI shapes rate selectivity for downward FM sweeps. A broader band of early LFI shapes direction selectivity. Here we asked whether these differences in LFI and HFI are present at the onset of hearing in the echolocation range or whether the differences develop slowly. We also studied how the development of properties of inhibitory frequencies influences FM rate and direction selectivity. We found that adult-like FM rate selectivity is present at 2 weeks after birth, whereas direction selectivity matures 12 weeks after birth. The different developmental time course for direction and rate selectivity is attributable to the differences in the development of LFI and HFI. Arrival time and bandwidth of HFI are adult-like at 2 weeks. Average arrival time of LFI gradually becomes faster and bandwidth becomes broader between 2 and 12 weeks. Thus, two properties of FM sweeps that are important for vocalization selectivity follow different developmental time courses attributable to the differences in the development of underlying inhibitory mechanisms.

Neural Mechanisms Underlying Selectivity for the Rate and Direction of Frequency-Modulated Sweeps in the Auditory Cortex of the Pallid Bat

Frequency-modulated (FM) sweeps are common in vocalizations, including human speech. Selectivity for FM sweep rate and direction is present in the auditory cortex of many species. The present study sought to determine the mechanisms underlying FM sweep selectivity in the auditory cortex of pallid bats. In the pallid bat inferior colliculus (IC), two mechanisms underlie selectivity for FM sweep rate. The first mechanism depends on duration tuning for tones that arises as a consequence of early inhibition generated by an excitatory tone. The second mechanism depends on a narrow band of delayed high-frequency inhibition. Direction selectivity depends on a broad band of early low-frequency inhibition. Here, the contributions of these mechanisms to cortical FM sweep selectivity were determined in pentobarbital-anesthetized pallid bats. We show that the majority of cortical neurons tuned to echolocation frequencies are selective for the downward direction and rate of FM sweeps. Unlike in IC neurons tuned in the echolocation range, duration tuning is rare in cortical neurons with similar tuning. As in the IC, consistent spectrotemporal differences exist between low- and high-frequency sidebands. A narrow band of delayed high-frequency inhibition is necessary for FM rate selectivity. Low-frequency inhibition has a broad bandwidth, early arrival time, and creates direction selectivity. Cortical neurons respond better to slower FM rates and exhibit broader rate tuning than IC neurons. Relative arrival time of high-frequency inhibition is slower in the cortex than in the IC. Thus whereas similar mechanisms shape direction selectivity of neurons tuned in the echolocation range in the IC and the cortex, only one of the two mechanisms underlying rate selectivity in the IC is present in the cortex.