Effects of changes in carrier frequency and modulation rate on unit responses in the inferior colliculus to amplitude-modulated sounds

Unit responses in the rat inferior colliculi to amplitude-modulated sounds were investigated. Two parameters of these sounds were varied: the modulation and carrier frequencies. The first ranged from 1–5 to 100 Hz, while the range of the second was determined by the frequency-threshold curve of the neuron. Other parameters of the amplitude-modulated stimulus (depth of modulation, level of carrier intensity) were kept as constant as possible. Characteristics of the unit response are determined by the nature of the combination of the carrier and modulation frequencies used. If the carrier frequency was optimal, the range of reproduction of the modulation frequencies, the number of spikes in the response, the duration of the response, and the corresponding stimulus duration were maximal; the response appeared at an earlier phase of the modulation cycle. A change in carrier frequency from optimal toward both higher and lower frequencies induced a regular change in all characteristics of the response: narrowing of the range of reproduction of the modulation rhythm amounting in some cases to total cessation of response, a decrease in the number of spikes per response, and shortening of the response in some cases as far as the appearance of only the initial response, while the response itself occurred in later phases of the modulation cycle.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 1, pp. 12–22, January–February, 1972.     

Effects of sound direction on the processing of amplitude-modulated signals in the frog inferior colliculus

Single-unit recordings were made from 143 neurons in the frog (Rana p. pipiens) inferior colliculus (IC) to investigate how free-field sound direction influenced neural responses to sinusoidal-amplitude-modulated (SAM) tone and/or noise. Modulation transfer functions (MTFs) were derived from 3 to 5 sound directions within 180° of frontal field. Five classes of MTF were observed: low-pass, high-pass, band-pass, multi-pass, and all-pass. For 64% of IC neurons, the MTF class remained unchanged when sound direction was shifted from contralateral 90° to ipsilateral 90°. However, the MTFs of more than half of these neurons exhibited narrower bandwidths when the loudspeaker was shifted to ipsilateral azimuths. There was a decrease in the cut-off frequency for neurons possessing low-pass MTFs, an increase in cut-off frequency for neurons showing high-pass MTFs, or a reduction in the pass-band for neurons displaying bandpass MTFs. These results suggest that sound direction can influence amplitude modulation (AM) frequency tuning of single IC neurons.Since changes in periodicity of SAM tones alter both the temporal parameters of sounds as well as the sound spectrum, we examined whether directional effects on spectral selectivity play a role in shaping the observed direction-dependent AM selectivity. The directional influence on AM selectivity to both SAM tone and SAM noise was measured in 62 neurons in an attempt to gain some insight into the mechanisms that underlie directionally-induced changes in AM selectivity. Direction-dependent changes in the shapes of the tone and noise derived MTFs were different for the majority of IC neurons (55/62) tested. These data indicate that a spectrally-based and a temporally-based mechanism may be responsible for the observed results.Abbreviations AM amplitude modulation - CF characteristic frequency - DI direction index - FR isointensity frequency response - GABA gamma-aminobutyric acid - IC inferior colliculus - ICc central nucleus of the inferior colliculus - ITD interaural time difference - MTF modulation transfer function - PSTH peri-stimulus time histogram - SAM sinusoidal-amplitude-modulated - SC synchronization coefficient - CN cochlear nucleus     

Deafness-related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity

The inferior colliculus (IC) is a major center of integration in the ascending as well as descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play a key role. When normal input to the auditory system is decreased, the balance between excitation and inhibition in the IC is disturbed. We examined global changes in gene expression in the rat IC 3 and 21 days following bilateral deafening, using Affymetrix GeneChip arrays and focused our analysis on changes in expression of neurotransmission-related genes. Over 1400 probe sets in the Affymetrix Rat Genome U34A Array were identified as genes that were differentially expressed. These genes encoded proteins previously reported to change as a consequence of deafness, such as calbindin, as well as proteins not previously reported to be modulated by deafness, such as clathrin. A subset of 19 differentially expressed genes was further examined using quantitative RT-PCR at 3, 21 and 90 days following deafness. These included several GABA, glycine, glutamate receptor and neuropeptide-related genes. Expression of genes for GABA-A receptor subunits beta2, beta3, and gamma2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor alpha1 initially declined and then later increased, while alpha2 increased sharply at 21 days. Glycine receptor alpha3 increased between 3 and 21 days, but decreased at 90 days. Of the neuropeptide-related genes tested with qRT-PCR, tyrosine hydroxylase decreased approximately 50% at all times tested. Serotonin receptor 2C increased at 3, 21, and 90 days. The 5B serotonin receptor decreased at 3 and 21 days and returned to normal by 90 days. Of the genes tested with qRT-PCR, only glycine receptor alpha2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptor beta3, GABA receptor gamma2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry.     

Neural modulation in inferior colliculus and central auditory plasticity

The neural modulation in central auditory system plays an important role in perception and processing of sound signal and auditory cognition. The inferior colliculus (IC) is both a relay station in central auditory pathway and a sub-cortical auditory center doing the sound signal processing. IC is also modulated by the descending projections from the cortex and auditory thalamus, medial geniculate body, and these neural modulations not only can affect ongoing sound signal processing but can also induce plastic changes in IC.     

Connections of superior olivary and inferior collicular neurons responding to amplitude-modulated stimuli by synchronized discharges in bats

Experiments on bats using the technique of anterograde and retrograde horseradish peroxidase transport showed that neurons of the superior olivary complex and inferior colliculus responding specifically to amplitude-modulated ultrasonic stimuli have projections to the oral reticular nucleus of the pons. Neurons of this part of the reticular formation respond to presentation of amplitude-modulated stimuli by a synchronization response, like neurons of specific auditory formations. It is concluded that the flow of action potentials from neurons coding amplitude modulation of the stimulus at the superio olivary and inferior collicular levels spreads outside the auditory system.A. A. Ukhtomskii Physiological Research Institute. A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 16, No. 6, pp. 800–807, November–December, 1984.     

Audiogenic epilepsy and GABAergic system of the colliculus inferior in Krushinsky-Molodkina rats

GABAergic brain system is an important link in the pathological circuits of rodent audiogenic epilepsy (AE). The number of GABAergic neurons in the inferior colliculi of KM strain rats (AE prone) was not different from that of the control non-prone strain. At the same time, the glutamate decarboxylase mRNA expression (the key enzyme of GABA synthesis) was 5 times higher than in control. The data evidence that the GABAergic system does play an important role in AE proneness.     

Neurons with different temporal firing patterns in the inferior colliculus of the little brown bat differentially process sinusoidal amplitude-modulated signals

We examined how well single neurons in the inferior colliculus (IC) of an FM bat (Myotis lucifugus) processed simple tone bursts of different duration and sinusoidal amplitude-modulated (SAM) signals that approximated passively heard natural sounds. Units' responses to SAM tones, measured in terms of average spike count and firing synchrony to the modulation envelope, were plotted as a function of the modulation frequency to construct their modulation transfer functions. These functions were classified according to their shape (e.g., band-, low-, high-, and all-pass). IC neurons having different temporal firing patterns to simple tone bursts (tonic, chopper, onset-late, and onset-immediate) exhibited different selectivities for SAM signals. All tonic and 83% of chopper neurons responded robustly to SAM signals and displayed a variety of spike count-based response functions. These neurons showed a decreased level of time-locking as the modulation frequency was increased, and thereby gave low-pass synchronization-based response functions. In contrast, 64% of onset-immediate, 37% of onset-late and 17% of chopper units failed to respond to SAM signals at any modulation frequency tested (5–800 Hz). Those onset neurons that did respond to SAM showed poor time-locking (i.e., non-significant levels of synchronization). We obtained evidence that the poor SAM response of some onset and chopper neurons was due to a preference for short-duration signals. These data suggest that tonic and most chopper neurons are better-suited for the processing of long-duration SAM signals related to passive hearing, whereas onset neurons are better-suited for the processing of short, pulsatile signals such as those used in echolocation.Abbreviations C chopper - FM frequency-modulated - IC inferior colliculus - MTF modulation transfer function - O₁ onset-immediate - O_L onset-late - PAM pulsatile amplitude-modulation - PSTH peri-stimulus time histogram - SAM sinusoidal amplitude-modulation - SC synchronization coefficient - T tonic     

Effect of sectioning the brachia of the inferior colliculi on the formation of auditory conditioned reflexes to amplitude-modulated stimuli

Elaboration of differentiation of tonal and amplitude-modulated stimuli with a frequency modulation of 5 Hz conducted on laboratory rats in five months after section of brachii colliculi proved to be impossible. The rate of correct reactions did not differ from the probability of random choice during 500 presentations of conditioned stimuli but significantly differed from the values obtained during differentiation of these signals in rats after control operation. Electrophysiological control showed that while in the control group and in intact animals at the presentation of amplitude-modulated stimuli with modulation frequency of 1-20 Hz summary potentials were recorded in the auditory cortex synchronized with their modulation frequency,--in rats after section of brachii colliculi only on- and off-responses were observed. It may be suggested that sensory providing of conditioned activity during the action of amplitude-modulated stimuli with low modulation frequency may be achieved only with the participation of specific pathways.     

Elevated levels of group-III metabotropic glutamate receptors in the inferior colliculus of genetically epilepsy-prone rats following intracollicular administration of l-serine-O-phosphate

The selective group-III metabotropic glutamate receptor agonist, L-serine-O-phosphate (L-SOP), when injected bilaterally into the inferior colliculus of the sound sensitive genetically epilepsy-prone (GEP) rats produces a short proconvulsant excitation followed by a long phase of protection against sound-induced seizures lasting for 2-4 days. We have studied this prolonged suppression of audiogenic seizures using pharmacological and molecular biological approaches including semiquantitative RT-PCR and western blotting. The intracerebroventricular injection of the protein synthesis inhibitor cycloheximide (120 microg) 30 min beforehand significantly reduces the proconvulsant seizure activity and the prolonged anticonvulsant effect of intracollicular L-SOP (500 nmol/side). The sensitive semiquantitative RT-PCR revealed a significant up-regulation in mGlu(4) and mGlu(7) mRNA levels in the inferior colliculus at 2 days (maximum suppression of audiogenic seizures) after intracollicular L-SOP injection compared with the non-injected, 2-day post-vehicle treated and 7-day (return to expressing audiogenic seizures) post-drug or vehicle-treated groups. No significant changes were observed in mGlu(6) or mGlu(8) mRNA expression levels in drug-treated compared with control groups. Examination of mGlu(4a) and mGlu(7a) protein levels using western blotting showed a significant increase in mGlu(7a) but no significant change in mGlu(4a) protein levels 2 days after L-SOP treatment compared with the control groups (non-injected and 2-day vehicle-injected group). These results suggest that up-regulation of mGlu(7) receptors is involved in the prolonged anticonvulsant effect of L-SOP against sound-induced seizures in GEP rats. The potential use of mGlu(7) agonists as novel anti-epileptic agents merits investigation.     

Coding of sinusoidally amplitude modulated acoustic stimuli in the inferior colliculus of the rufous horseshoe bat,Rhinolophus rouxi

Summary Single neuron responses to sinusoidally amplitude modulated (SAM) signals were studied in the inferior colliculus of the horseshoe bat,Rhinolophus rouxi.57% of the neurons responded to SAM stimuli with periodical discharges synchronized to the modulation cycle. The proportion of cells driven by amplitude modulated signals was independent of the best frequency of the neurons. Best modulation frequencies were at or below 100 Hz in about 70% of the neurons. Synchronized activity could be elicited by modulation frequencies up to 400 Hz.Best SAM responses were observed at stimulus intensities 10 dB above threshold. Generally the BMF of a neuron did not change with intensity. The BMF decreased with decreasing modulation depth of the amplitude modulation.A trend for a topographical organization of neurons according to best modulation frequencies was detected. The results did not reveal any significant specialization of the bat's auditory system for coding of amplitude modulations as compared to other mammals.Abbreviations BF best frequency - BMF best modulation frequency - CF constant frequency - FM frequency modulation - IC inferior colliculus - SAM sinusoidal amplitude modulation - SFM sinusoidal frequency modulation     

Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies

The Kv3.1 potassium channel is expressed at high levels in auditory nuclei and contributes to the ability of auditory neurons to fire at high frequencies. We have tested the effects of streptomycin, an agent that produces progressive hearing loss, on the firing properties of inferior colliculus neurons and on Kv3.1 currents in transfected cells. We found that in inferior colliculus neurons, intracellular streptomycin decreased the current density of a high threshold, noninactivating outward current and reduced the rate of repolarization of action potentials and the ability of these neurons to fire at high frequencies. Furthermore, potassium current in CHO cells transfected with the Kv3.1 gene was reduced by 50% when cells were cultured in the presence of streptomycin or when streptomycin was introduced intracellularly in the pipette solution. In the presence of intracellular streptomycin, the activation rate of Kv3.1 current increased and inhibition by extracellular TEA become voltage-dependent. The data indicate that streptomycin inhibits Kv3.1 currents by inducing a conformational change in the Kv3.1 channel. The hearing loss caused by aminoglycoside antibiotics may be partially mediated by their inhibition of Kv3.1 current in auditory neurons.     

Responses of neurons in the rat auditory and associative cortices to tonal stimuli

Activity of single neurons and mass evoked potentials (EP) were recorded from the auditory (area 41) and associative (area 39) cortices in acute experiments on rats anesthetized with urethane, nembutal, or chloralose; pure tones were used as acoustic stimuli. The EP appearing in response to a wide range of sound tones on the surface of the auditory and associative cortices were dissimilar in their latency and shape. For neurons exhibiting stable responses, the frequency-threshold curves (FTC) were plotted.Weak and variable responses of neurons were observed under slight urethane anesthesia. Nembutal anesthesia increased the responsiveness of neurons and the probability of appearing of late components in the responses. Chloralose anesthesia was characterized by extension of frequency range perceived by a neuron, while its sharpness of tuning remained unchanged. Under all types of anesthesia employed, the responses recorded from the associative cortex neurons had longer latencies than those recorded from the auditory cortex neurons. Neurons exhibiting the frequency selectivity were much less numerous in the associative cortex than in the auditory cortex. The former neurons were often characterized by intermittent FTC and they responded to a more extended frequency range. No clear tonotopic organization was found in the associative cortex.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp. 343–349, September–October, 1993.     

Evoked potentials of the cat inferior colliculus to acoustic stimuli simulating sound source movement with different velocities in opposite directions

Amplitude changes of inferior colliculus evoked potentials (EPs) in anaesthetized adult cats were studied under presentation of acoustic stimuli simulating both azimuth-moving and stationary sound source. The movement was simulated with gradual changes of interaural time delay between binaurally presented click trains. It was shown that the amplitude of EPs elicited by "moving" signals depended on the velocity of movement. Amplitude differences between EPs to "moving" and stationary stimuli were observed under motion velocities up to 320 deg./s. The greatest response amplitudes in different experiments took place under velocities within the range of 67-320 deg./s with most of them recorded under velocities of 170 and 125 deg./s. Amplitude of the responses to lateral-medial movement with any velocity were always greater than those to opposite direction of movement with the same velocity.     

Ascending and descending projections to the inferior colliculus in the rat

The ascending and descending projections to the central nucleus of the inferior colliculus (IC) were studied with the aid of retrograde transport of horseradish peroxidase (HRP). HRP-labelled cells were found in contralateral cochlear nuclei, where the majority of different cell types was stained. Few labelled cells were observed in the ipsilateral cochlear nuclei. HRP-positive neurones were found in all nuclei of the superior olivary complex on the ipsilateral side with the exception of the medial nucleus of the trapezoid body, which was never labelled either ipsilaterally or contralaterally. The largest concentration of HRP-labelled cells was usually observed in the ipsilateral superior olivary nucleus. Smaller numbers of labelled cells were present in contralateral nuclei of the superior olivary complex. Massive projections to the inferior colliculus were found from the contralateral and ipsilateral dorsal nucleus of the lateral lemniscus and ipsilateral ventral nucleus of the lateral lemniscus. Many neurones of the central and external nuclei of the contralateral inferior colliculus were labelled with HRP. Topographic organisation of the pathways ascending to the colliculus was expressed in the cochlear nuclei, lateral superior olivary nucleus and in the dorsal nucleus of the lateral lemniscus. HRP--positive cells were found in layer V of the ipsilateral auditory cortex, however, the evidence for topographic organisation was lacking.     

Spontaneous sister-chromatid exchange frequencies in human B and T lymphocytes at BrdU borderline concentrations for sister-chromatid differentiation

Human peripheral blood B and T lymphocytes, highly purified by immunologic methods, were supplemented with gamma-irradiated unseparated autologous mononuclear cells to restore helper functions and stimulated with pokeweed mitogen and phytohemagglutinin, respectively. Spontaneous sister-chromatid exchange (SCE) frequencies were investigated in proliferating B and T lymphocyte cultures labeled with the cell-type-specific borderline concentrations of 5-bromodeoxyuridine (BrdU) for sister-chromatid differentiation (SCD). B lymphocytes from 6 different donors showed mean values of 3.28-3.72 SCE events/cell. In T lymphocytes, mean values of 6.30-7.28 SCEs/cell were observed. The differences between the SCE distributions of the cell populations are highly significant. The results show that the differences in the spontaneous SCE frequencies between human B and T lymphocytes were not due to a difference in the uptake of BrdU.     

Corticofugal regulation of auditory sensitivity in the bat inferior colliculus

Under free-field stimulation conditions, corticofugal regulation of auditory sensitivity of neurons in the central nucleus of the inferior colliculus of the big brown bat, Eptesicus fuscus, was studied by blocking activities of auditory cortical neurons with Lidocaine or by electrical stimulation in auditory cortical neuron recording sites. The corticocollicular pathway regulated the number of impulses, the auditory spatial response areas and the frequency-tuning curves of inferior colliculus neurons through facilitation or inhibition. Corticofugal regulation was most effective at low sound intensity and was dependent upon the time interval between acoustic and electrical stimuli. At optimal interstimulus intervals, inferior colliculus neurons had the smallest number of impulses and the longest response latency during corticofugal inhibition. The opposite effects were observed during corticofugal facilitation. Corticofugal inhibitory latency was longer than corticofugal facilitatory latency. Iontophoretic application of γ-aminobutyric acid and bicuculline to inferior colliculus recording sites produced effects similar to what were observed during corticofugal inhibition and facilitation. We suggest that corticofugal regulation of central auditory sensitivity can provide an animal with a mechanism to regulate acoustic signal processing in the ascending auditory pathway. Accepted: 15 July 1998     

Role of the geniculate body in performing conditioned reflexes to amplitude-modulated stimuli in the rat

In 13 laboratory rats with bilateral auditory cortex ablation, the border frequency of amplitude-modulation still allowing differentiation between tonal and amplitude-modulated stimuli, did not change after bilateral section of the brachii of the posterior colliculi. Bilateral auditory cortex ablation and section of the brachii drastically disturbed this differentiation when the modulation frequencies were higher than 27-31 Hz. The data suggest that the completion of coding of amplitude-modulated stimuli does not take place at the level of the medial geniculate body, and that border frequencies defined after auditory cortex ablation are linked with the frontier posterior colliculi--thalamo-cortical system.     

Unit responses of the inferior colliculi to changes in the intensity of an amplitude-modulated signal

Unit responses of the inferior colliculi of anesthetized rats to amplitude-modulated sounds during a change in the carrier intensity were investigated. The following unit response characteristics were assessed: the number of spikes in the response, the range of reproduction of the modulation frequency, the response duration, and the pattern of the spike response relative to the envelope of the amplitude-modulated stimulus. The following parameters of the stimulus were varied: carrier intensity (usually of optimal frequency or noise), frequency of modulation (from 2 to 100 Hz), and carrier frequency. With a decrease in the intensity of the carrier in the case of monotonic neurons, and also with an increase or decrease in the intensity of the carrier relative to its optimal level in nonmonotonic neurons, the following changes in the discharge were regularly observed: the number of spikes in the response and its duration were reduced down to the appearance of only one initial response, the range of reproduction of the rhythm of modulation was narrowed, and the response pattern was sharply modified.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR. I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 4, pp. 355–366, July–August, 1973.