Responses of young and aged rat inferior colliculus neurons to sinusoidally amplitude modulated stimuli.

The inferior colliculus (IC) is a processing center for monaural and binaural auditory signals. Many units in the central nucleus of the inferior colliculus (CIC) respond to amplitude and frequency modulated tones, features found in communication signals. The present study examined potential effects of age on responses to sinusoidally amplitude modulated (SAM) tones in CIC and external cortex of the inferior colliculus (ECIC) units in young and aged F344 rats. Extracellular recordings from 154 localized single units of aged (24 month) rats were compared to recordings from 135 IC units from young adult (3 month) animals. SAM tones were presented at 30 dB above threshold. Comparisons were made between CIC and ECIC regarding the percentage of units responding to SAM stimuli, the relationship between SAM responsiveness and temporal response patterns, maximum discharge rates and maximum modulation gains, shapes of rate transfer functions and synchronization modulation transfer functions (MTFs) in response to SAM tones. Sixty percent of units in young and aged rat IC were selectively responsive to SAM stimuli. Eighty-one percent of units classified as onset temporal response patterns were not tonically responsive to SAM stimuli. Median maximum discharge rate in response to SAM tones was 17.6/s in young F344 rats; median maximum modulation gain was 3.85 dB. These measurements did not change significantly with age. Thirty-seven percent of young rat units displayed bandpass MTFs and 53% had lowpass MTFs. There was a significant age-related shift in the distribution of MTF shapes in both the CIC and ECIC. Aged animals showed a lower percentage of bandpass functions and a higher percentage of lowpass functions. Age-related changes observed in SAM coding may reflect an altered balance between excitatory/inhibitory neurotransmitter efficacy in the aged rat IC, and/or possibly a change in the functional dynamic range of IC neurons.

Gamma-aminobutyric acidergic and glycinergic inputs shape coding of amplitude modulation in the chinchilla cochlear nucleus.

Amplitude modulation is a prominent acoustic feature of biologically relevant sounds, such as speech and animal vocalizations. Enhanced temporal coding of amplitude modulation signals is found in certain dorsal and posteroventral cochlear nucleus neurons when they are compared to auditory nerve. Although mechanisms underlying this improved temporal selectivity are not known, involvement of inhibition has been suggested. gamma-Aminobutyric acid- and glycine-mediated inhibition have been shown to shape the dorsal cochlear nucleus and posteroventral cochlear nucleus response properties to other acoustic stimuli. In the present study, responses to amplitude modulation tones were obtained from chinchilla dorsal cochlear nucleus and posteroventral cochlear nucleus neurons. The amplitude modulation carrier was set to the neuron's characteristic frequency and the modulating frequency varied from 10 Hz. Rate and temporal modulation transfer functions were compared across neurons. Bandpass temporal modulation transfer functions were observed in 74% of the neurons studied. Most cochlear nucleus neurons (90%) displayed flat or lowpass rate modulation transfer functions to amplitude modulation signals presented at 2540 dB (re: characteristic frequency threshold). The role of inhibition in shaping responses to amplitude modulation stimuli was examined using iontophoretic application of glycine or gamma-aminobutyric acidA receptor agonists and antagonists. Blockade of gamma-aminobutyric acidA or glycine receptors increased stimulus-evoked discharge rates for a majority of neurons tested. Synchronization to the envelope was reduced, particularly at low and middle modulating frequencies, with temporal modulation transfer functions becoming flattened and less bandpass in appearance. Application of glycine, gamma-aminobutyric acid or muscimol increased the modulation gain over the low- and mid-modulation frequencies and reduced the discharge rate across envelope frequencies for most neurons tested. These findings support the hypothesis that glycinergic and gamma-aminobutyric acidergic inputs onto certain dorsal cochlear nucleus and posteroventral cochlear nucleus neurons play a role in shaping responses to amplitude modulation stimuli and may be responsible for the reported preservation of amplitude modulation temporal coding in dorsal cochlear nucleus and posteroventral cochlear nucleus neurons at high stimulus intensities or in background noise.

Glycinergic and GABAergic inputs affect short-term suppression in the cochlear nucleus.

Most cochlear nucleus (CN) neurons exhibit short-term response suppression to a second stimulus in a paired-pulse (click), forward-masking, paradigm. The magnitude of suppression, which appears to be greater than that observed in acoustic nerve, is dependent on the temporal separation and/or relative intensities of the two stimuli. Recent evidence suggests that inhibitory circuitry ending on CN neurons may mediate this response suppression. Using extracellular recordings from single CN neurons, suppression was evaluated using a forward-masking paradigm. Responses to paired acoustic clicks (i.e., a 'masker' followed by an identical 'probe' click) were measured while the time interval between the masker and probe was varied systematically. The role of inhibitory circuitry in forward-masking in the CN was assessed by pharmacologic manipulation of the GABA(A) and glycine(I) (strychnine-sensitive) receptors. Blockade of glycinergic or GABAergic receptors by iontophoretic application of the antagonists, strychnine and bicuculline methiodide, decreased the effects of forward-masking by shortening recovery times of the probe response in 2/3 of the neurons tested. Conversely, agonist application (glycine, and GABA or muscimol) increased the magnitude of suppression and delayed recovery of the probe response relative to control values. These findings suggest that known circuits releasing glycine and/or GABA mediate short-term response suppression in some CN neurons.

Inhibitory inputs modulate discharge rate within frequency receptive fields of anteroventral cochlear nucleus neurons.

1. The amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine function as inhibitory neurotransmitters associated with nonprimary inputs onto spherical bushy and stellate cells, two principal cell types located in the anteroventral cochlear nucleus (AVCN). These neurons are characterized by primary-like (including phase-locked) and chopper temporal response patterns, respectively. 2. Inhibition directly adjacent to the excitatory response area has been hypothesized to sharpen or limit the breadth of the tonal frequency receptive field. This study was undertaken to test whether GABA and glycine circuits function primarily to sharpen the lateral edges of the tonal excitatory response area or to modulate discharge rate within central portions of the excitatory response area of AVCN neurons. 3. To test this, iontophoretic application of the glycineI antagonist, strychnine, or the GABAA antagonist, bicuculline, was used to block inhibitory inputs after obtaining control families of isointensity contours (response areas) from extracellularly recorded AVCN neurons. 4. Blockade of GABA and/or glycine inputs was found to increase discharge rate primarily within the excitatory response area of neurons displaying chopper and primary-like temporal responses with little or no change in bandwidth or in off-characteristic frequency (CF) discharge rate. 5. The principal sources of inhibitory inputs onto AVCN neurons are cells located in the dorsal cochlear nucleus and superior olivary complex, which appear to be tonotopically matched to their targets. In agreement with these morphological studies, the data presented in this paper suggest that most GABA and/or glycine inhibition is tonotopically aligned with excitatory inputs. 6. These findings support models that suggest that GABA and/or glycine inputs onto AVCN neurons are involved in circuits that adjust gain to enable the detection of signals in noise by enhancing signal relative to background.

Paired tone facilitation in dorsal cochlear nucleus neurons: a short-term potentiation model testable in vivo.

It has been suggested that the dorsal cochlear nucleus (DCN) is involved in coding stimulus history or prior auditory activity [Manis (1989) J. Neurophys., 61, 149-161; Manis (1990) J. Neurosci., 10, 2338-2351]. The major output neurons of the DCN are the fusiform (pyramidal) cells which are thought to receive excitatory inputs from the descending branch of the acoustic nerve onto their basal dendrites and significant inhibitory glycinergic and GABAergic inputs to the soma and dendrites. The apical dendrites of these neurons lie within the molecular layer of the DCN and encounter parallel fibers which are thought to utilize the excitatory amino acid neurotransmitter glutamate. In this study of anesthetized chinchillas, we found that, in contrast to the responses of acoustic nerve fibers and most cochlear nucleus neurons which are masked by an appropriate preceding signal, many DCN principal cells are facilitated during the second of two identical stimuli. Facilitated DCN responses often have a reduced interspike interval and a more chopper-like temporal response pattern to the second characteristic frequency tone. This paired tone facilitation in the chinchilla DCN provides as in vivo model of short-term potentiation elicited by sensory stimulation similar to the paired-pulse facilitation observed with electrical stimulation in other models.

Age-related changes in auditory brainstem responses in Fischer 344 rats: effects of rate and intensity.

Age-related changes in auditory brainstem responses (ABR) observed in humans may reflect peripheral or centrally-occurring deficits. In clinical studies, high stimulus repetition rates have been used to improve the identification of central auditory pathology. In the present study, interactions between stimulus level and repetition rate were examined in the Fischer 344 rat, an animal demonstrating both peripheral hearing loss and changes in auditory brainstem neurochemistry with age. Monaural threshold and standard ABR morphology were determined in young (3-6 months) and old (20-23 months) rats using clicks at 10/s, with intensity varied from 0-100 dB. The effects of increasing stimulus repetition rate on ABR latency and morphology were evaluated at 60-100 dB using rates of 5, 10, 20, and 40/s. Old animals demonstrated elevated ABR click thresholds, reflected by shifts in the latency-intensity curves. With increased stimulation rates, aged rats exhibited prolonged Wave 4 and 5 latencies, especially at the highest intensities, with degraded waveform morphology. Peak amplitudes were generally reduced in old rats, irrespective of rate or stimulus level. These findings suggest auditory processing is altered in aged animals, while the selective effects of rate increases on Waves 4 and 5 provide supporting evidence for possible involvement of the central auditory generators of these components.

A spectrotemporal analysis of DCN single unit responses to wideband noise in guinea pig.

Spectrotemporal receptive fields (STRFs) were estimated for chopper and pauser units recorded in guinea pig dorsal cochlear nucleus (DCN). Sixteen wideband, periodic noise stimuli, represented as time-frequency surfaces of energy density, were cross correlated in time with the unit's corresponding period histograms to determine if specific energy patterns tended to precede spike occurrence. The STRFs obtained were unique to the DCN, as compared to the ventral cochlear nucleus (VCN) [Clopton and Backoff, 1991, Hear. Res. 52, 329-344] in their degree of temporal and spectral complexity. Certain unit response types, classified from their peristimulus-time histograms (PSTHs) to tonebursts, were associated with distinctive patterns in the STRFs. All STRFs had at least one region of elevated energy density (peak region) closely preceding spike occurrence, which may reflect a short-pathway, primary excitatory input (or inputs) to the neuron. In addition, some units displayed low-energy regions (troughs) with greater temporal precedences on their STRFs, particularly when higher stimulus intensities were used. This analysis approach appears to have potential for investigating functional neural connectivity and predicting responses to novel complex stimuli, although specific implementations of the technique impose limitations on the interpretation of results.

Spectrotemporal receptive fields of neurons in cochlear nucleus of guinea pig.

Spectrotemporal receptive fields (STRFs) [Hermes et al., Hear. Res. 5, 147-178, 1981] for neurons in the cochlear nuclei (CN) of guinea pig were estimated. Sixteen periodic segments of bandlimited, synthesized noise evoked replicable, distinctive period histograms for spike discharges. All driven units in the major divisions of the CN having their characteristic frequency (CF) within the noise bandlimits had unique STRFs for a given intensity of noise stimulation. The STRF maximum corresponded to the unit's CF, and details of the STRF patterns differed over CN divisions and response classes derived from tonebursts. The sizes of features in STRFs from this mammal appeared significantly smaller in their temporal and spectral extents than those reported in the torus semicircularis of an amphibian and were roughly comparable to the few units reported from cat ventral CN [Eggermont et al., Quart. Rev. Biophys. 16, 341-414, 1983]. STRFs, as they are presently obtained, provide useful insight into some aspects of afferent processing and perhaps connectivity, but their interpretation is specific to the level of stimulation and limited by the need to choose a specific energy distribution to represent the stimulus.