GINA. Artículos

Physiological properties of auditory neurons responding to omission deviants in the anesthetized rat

2024-01-01T00:00:00Z

The detection of novel, low probability events in the environment is critical for survival. To perform this vital task, our brain is continuously building and updating a model of the outside world; an extensively studied phenomenon commonly referred to as predictive coding. Predictive coding posits that the brain is continuously extracting regularities from the environment to generate predictions. These predictions are then used to supress neuronal responses to redundant information, filtering those inputs, which then automatically enhances the remaining, unexpected inputs. We have recently described the ability of auditory neurons to generate predictions about expected sensory inputs by detecting their absence in an oddball paradigm using omitted tones as deviants. Here, we studied the responses of individual neurons to omitted tones by presenting individual sequences of repetitive pure tones, using both random and periodic omissions, presented at both fast and slow rates in the inferior colliculus and auditory cortex neurons of anesthetized rats. Our goal was to determine whether feature-specific dependence of these predictions exists. Results showed that omitted tones could be detected at both high (8 Hz) and slow repetition rates (2 Hz), with detection being more robust at the non-lemniscal auditory pathway.

Neural correlates of novelty detection in the primary auditory cortex of behaving monkeys

2024-01-01T00:00:00Z

The neural mechanisms underlying novelty detection are not well understood, especially in relation to behavior. Here, we present single-unit responses from the primary auditory cortex (A1) from two monkeys trained to detect deviant tones amid repetitive ones. Results show that monkeys can detect deviant sounds, and there is a strong correlation between late neuronal responses (250–350 ms after deviant onset) and the monkeys’ perceptual decisions. The magnitude and timing of both neuronal and behavioral responses are increased by larger frequency differences between the deviant and standard tones and by increasing the number of standard tones preceding the deviant. This suggests that A1 neurons encode novelty detection in behaving monkeys, influenced by stimulus relevance and expectations. This study provides evidence supporting aspects of predictive coding in the sensory cortex.

Effects of Multisession Anodal Electrical Stimulation of the Auditory Cortex on Temporary Noise-Induced Hearing Loss in the Rat

2021-01-01T00:00:00Z

The protective effect of the efferent system against acoustic trauma (AT) has been shown by several experimental approaches, including damage to one ear, sectioning of the olivocochlear bundle (OCB) in the floor of the IV ventricle, and knock-in mice overexpressing outer hair cell (OHC) cholinergic receptors, among others. Such effects have been related to changes in the regulation of the cholinergic efferent system and in cochlear amplification, which ultimately reverse upon protective hearing suppression. In addition to well-known circuits of the brainstem, the descending corticofugal pathway also regulates efferent neurons of the olivary complex. In this study, we applied our recently developed experimental paradigm of multiple sessions of electrical stimulation (ES) to activate the efferent system in combination with noise overstimulation. ABR thresholds increased 1 and 2 days after AT (8–16 kHz bandpass noise at 107 dB for 90 min) recovering at AT + 14 days. However, after multiple sessions of epidural anodal stimulation, no changes in thresholds were observed following AT. Although an inflammatory response was also observed 1 day after AT in both groups, the counts of reactive macrophages in both experimental conditions suggest decreased inflammation in the epidural stimulation group. Quantitative immunocytochemistry for choline acetyltransferase (ChAT) showed a significant decrease in the size and optical density of the efferent terminals 1 day after AT and a rebound at 14 days, suggesting depletion of the terminals followed by a long-term compensatory response. Such a synthesis recovery was significantly higher upon cortical stimulation. No significant correlation was found between ChAT optical density and size of the buttons in sham controls (SC) and ES/AT + 1day animals; however, significant negative correlations were shown in all other experimental conditions. Therefore, our comparative analysis suggests that cochleotopic cholinergic neurotransmission is also better preserved after multisession epidural stimulation.

Reversible Functional Changes Evoked by Anodal Epidural Direct Current Electrical Stimulation of the Rat Auditory Cortex

2019-01-01T00:00:00Z

Rat auditory cortex was subjected to 0.1 mA anodal direct current in seven 10-min sessions on alternate days. Based on the well-known auditory cortex control of olivocochlear regulation through corticofugal projections, auditory brainstem responses (ABRs) were recorded as an indirect test of the effectiveness and reversibility of the multisession protocol of epidural stimulation. Increases of 20–30 dB ABR auditory thresholds shown after epidural stimulation reverted back to control levels 10 min after a single session. However, increases in thresholds revert 4 days after multisession stimulation. Less changes in wave amplitudes and threshold shifts were shown in ABR recorded contralaterally to the electrically stimulated side of the brain. To assess tissue effects of epidural electric stimulation on the brain cortex, well characterized functional anatomical markers of glial cells (GFAP/astrocytes and Iba1/microglial cells) and neurons (c-Fos) were analyzed in alternate serial sections by quantitative immunocytochemistry. Restricted astroglial and microglial reactivity was observed within the cytoarchitectural limits of the auditory cortex. However, interstitial GFAP overstaining was also observed in the ventricular surface and around blood vessels, thus supporting a potential global electrolytic stimulation of the brain. These results correlate with extensive changes in the distribution of c-Fos immunoreactive neurons among layers along sensory cortices after multisession stimulation. Quantitative immunocytochemical analysis supported this idea by showing a significant increase in the number of positive neurons in supragranular layers and a decrease in layer 6 with no quantitative changes detected in layer 5. Our data indicate that epidural stimulation of the auditory cortex induces a reversible decrease in hearing sensitivity due to local, restricted epidural stimulation. A global plastic response of the sensory cortices, also reported here, may be related to electrolytic effects of electric currents.

Deviance detection in physiologically identified cell types in the rat auditory cortex

2021-01-01T00:00:00Z

Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection. In order to understand the circuitry responsible for deviance detection in the auditory cortex (AC), it is necessary to determine the properties of excitatory and inhibitory neurons separately. Measuring the spike widths of neurons recorded extracellularly from the anaesthetized rat AC, we classified them as fast spiking or regular spiking units. These two neuron types are generally considered as putative inhibitory or excitatory, respectively. In response to an oddball paradigm, we found that both types of units showed similar amounts of deviance detection overall. When considering each AC field separately, we found that only in A1 fast spiking neurons showed higher deviance detection levels than regular spiking neurons, while in the rest of the fields there was no such distinction. Interpreting these responses in the context of the predictive coding framework, we found that the responses of both types of units reflect mainly prediction error signaling (i.e., genuine deviance detection) rather than repetition suppression.

Adaptation in the auditory system: an overview

2014-02-21T00:00:00Z

The early stages of the auditory system need to preserve the timing information of sounds in order to extract the basic features of acoustic stimuli. At the same time, different processes of neuronal adaptation occur at several levels to further process the auditory information. For instance, auditory nerve fiber responses already experience adaptation of their firing rates, a type of response that can be found in many other auditory nuclei and may be useful for emphasizing the onset of the stimuli. However, it is at higher levels in the auditory hierarchy where more sophisticated types of neuronal processing take place. For example, stimulus-specific adaptation, where neurons show adaptation to frequent, repetitive stimuli, but maintain their responsiveness to stimuli with different physical characteristics, thus representing a distinct kind of processing that may play a role in change and deviance detection. In the auditory cortex, adaptation takes more elaborate forms, and contributes to the processing of complex sequences, auditory scene analysis and attention. Here we review the multiple types of adaptation that occur in the auditory system, which are part of the pool of resources that the neurons employ to process the auditory scene, and are critical to a proper understanding of the neuronal mechanisms that govern auditory perception.

Pattern-sensitive neurons reveal encoding of complex auditory regularities in the rat inferior colliculus

2019-01-01T00:00:00Z

A ‘pattern alternation paradigm’ has been previously used in human ERP recordings to investigate the brain encoding of complex auditory regularities, but prior studies on regularity encoding in animal models to examine mechanisms of adaptation of auditory neuronal responses have used primarily oddball stimulus sequences to study stimulus-specific adaptation alone. In order to examine the sensitivity of neuronal adaptation to expected and unexpected events embedded in a complex sound sequence, we used a similar patterned sequence of sounds. We recorded single unit activity and compared neuronal responses in the rat inferior colliculus (IC) to sound stimuli conforming to pattern alternation regularity with those to stimuli in which occasional sound repetitions violated that alternation. Results show that some neurons in the rat inferior colliculus are sensitive to the history of patterned stimulation and to violations of patterned regularity, demonstrating that there is a population of subcortical neurons, located as early as the level of the midbrain, that can detect more complex stimulus regularities than previously supposed and that are as sensitive to complex statistics as some neurons in primary auditory cortex. Our findings indicate that these pattern-sensitive neurons can extract temporal and spectral regularities between successive acoustic stimuli. This is important because the extraction of regularities from the sound sequences will result in the development of expectancies for future sounds and hence, the present results are compatible with predictive coding models. Our results demonstrate that some collicular neurons, located as early as in the midbrain level, are involved in the generation and shaping of prediction errors in ways not previously considered and thus, the present findings challenge the prevailing view that perceptual organization of sound only emerges at the auditory cortex level.

Extracellular Recording of Neuronal Activity Combined with Microiontophoretic Application of Neuroactive Substances in Awake Mice

2016-05-21T00:00:00Z

Differences in the activity of neurotransmitters and neuromodulators, and consequently different neural responses, can be found between anesthetized and awake animals. Therefore, methods allowing the manipulation of synaptic systems in awake animals are required in order to determine the contribution of synaptic inputs to neuronal processing unaffected by anesthetics. Here, we present methodology for the construction of electrodes to simultaneously record extracellular neural activity and release multiple neuroactive substances at the vicinity of the recording sites in awake mice. By combining these procedures, we performed microiontophoretic injections of gabazine to selectively block GABAA receptors in neurons of the inferior colliculus of head-restrained mice. Gabazine successfully modified neural response properties such as the frequency response area and stimulus-specific adaptation. Thus, we demonstrate that our methods are suitable for recording single-unit activity and for dissecting the role of specific neurotransmitter receptors in auditory processing. The main limitation of the described procedure is the relatively short recording time (~3 hr), which is determined by the level of habituation of the animal to the recording sessions. On the other hand, multiple recording sessions can be performed in the same animal. The advantage of this technique over other experimental procedures used to manipulate the level of neurotransmission or neuromodulation (such as systemic injections or the use of optogenetic models), is that the drug effect is confined to the local synaptic inputs to the target neuron. In addition, the custom-manufacture of electrodes allows adjustment of specific parameters according to the neural structure and type of neuron of interest (such as the tip resistance for improving the signal-to-noise ratio of the recordings).

Variability of the time course of stimulus-specific adaptation in the inferior colliculus

2012-12-27T00:00:00Z

Stimulus-specific adaptation (SSA) is the ability of some neurons to respond better to rare than to frequent, repetitive stimuli. In the auditory system, SSA has been found at the level of the midbrain, thalamus, and cortex. While previous studies have used the whole overall neuronal response to characterize SSA, here we present a detailed analysis on the variations within the time course of the evoked responses. The extracellular activity of well isolated single neurons from the inferior colliculus (IC) was recorded during stimulation using an oddball paradigm, which is able to elicit SSA. At the same time, these responses were evaluated before, during, and after the microiontophoretic application of gabazine, a specific antagonist of GABAA receptors, to study the contribution of inhibition to the responses of these neurons. We then analyzed the difference signal (DS), which is the difference in the PSTH in response to rare and frequent stimuli. We found that, even in a sample of neurons showing strong SSA (i.e., showing larger preference for rare stimuli), the DS was variable and one third of the neurons contained portions that responded significantly better to the frequent stimuli than to the rare. This variability is not observed when averaging the responses of multiple cells. Furthermore, the blockade of GABAA receptors increased the number of neurons showing portions that responded better to the frequent stimuli, indicating that inhibition in the IC refines and sharpens SSA in the neural responses.

GABAA-Mediated Inhibition Modulates Stimulus-Specific Adaptation in the Inferior Colliculus

2012-03-29T00:00:00Z

The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABAA-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABAA receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABAA-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron.

Topographic Distribution, Frequency, and Intensity Dependence of Stimulus-Specific Adaptation in the Inferior Colliculus of the Rat

2012-12-05T00:00:00Z

The ability to detect unexpected sounds within the environment is an important function of the auditory system, as a rapid response may be required for the organism to survive. Previous studies found a decreased response to repetitive stimuli (standard), but an increased response to rare or less frequent sounds (deviant) in individual neurons in the inferior colliculus (IC) and at higher levels. This phenomenon, known as stimulus-specific adaptation (SSA) has been suggested to underpin change detection. Currently, it is not known how SSA varies within a single neuron receptive field, i.e., it is unclear whether SSA is a unique property of the neuron or a feature that is frequency and/or intensity dependent. In the present experiments, we used the common SSA index (CSI) to quantify and compare the degree of SSA under different stimulation conditions in the IC of the rat. We calculated the CSI at different intensities and frequencies for each individual IC neuron to map the neuronal CSI within the receptive field. Our data show that high SSA is biased toward the high-frequency and low-intensity regions of the receptive field. We also find that SSA is better represented in the earliest portions of the response, and there is a positive correlation between the width of the frequency response area of the neuron and the maximum level of SSA. The present data suggest that SSA in the IC is not mediated by the intrinsic membrane properties of the neurons and instead might be related to an excitatory and/or inhibitory input segregation.

A biologically inspired spiking neural network model of the auditory midbrain for sound source localisation

2010-12-01T00:00:00Z

This paper proposes a spiking neural network (SNN) of the mammalian subcortical auditory pathway to achieve binaural sound source localisation. The network is inspired by neurophysiological studies on the organisation of binaural processing in the medial superior olive (MSO), lateral superior olive (LSO) and the inferior colliculus (IC) to achieve a sharp azimuthal localisation of a sound source over a wide frequency range. Three groups of artificial neurons are constructed to represent the neurons in the MSO, LSO and IC that are sensitive to interaural time difference (ITD), interaural level difference (ILD) and azimuth angle (θ), respectively. The neurons in each group are tonotopically arranged to take into account the frequency organisation of the auditory pathway. To reflect the biological organisation, only ITD information extracted by the MSO is used for localisation of low frequency (< 1 kHz) sounds; for sound frequencies between 1 and 4 kHz the model also uses ILD information extracted by the LSO. This information is combined in the IC model where we assume that the strengths of the inputs from the MSO and LSO are proportional to the conditional probability of P(θ|ITD) or P(θ|ILD) calculated based on the Bayes theorem. The experimental results show that the addition of ILD information significantly increases sound localisation performance at frequencies above 1 kHz. Our model can be used to test different paradigms for sound localisation in the mammalian brain, and demonstrates a potential practical application of sound localisation for robots.

A biomimetic spiking neural network of the auditory midbrain for mobile robot sound localisation in reverberant environments

2009-07-31T00:00:00Z

This paper proposes a spiking neural network (SNN) of the mammalian auditory midbrain to achieve binaural sound source localisation with a mobile robot. The network is inspired by neurophysiological studies on the organisation of binaural processing in the medial superior olive (MSO), lateral superior olive (LSO) and the inferior colliculus (IC) to achieve a sharp azimuthal localisation of sound source over a wide frequency range in situations where there is auditory clutter and reverberation. Three groups of artificial neurons are constructed to represent the neurons in the MSO, LSO and IC that are sensitive to interaural time difference (ITD), interaural level difference (ILD) and azimuth angle respectively. The ITD and ILD cues are combined in the IC using Bayes's theorem to estimate the azimuthal direction of a sound source. Two of known IC cells, onset and sustained-regular are modelled. The azimuth estimations at different robot positions are then used to calculate the sound source position by a triangulation method using an environment map constructed by a laser scanner. The experimental results show that the addition of ILD information significantly increases sound localisation performance at frequencies above 1 kHz. The mobile robot is able to localise a sound source in an acoustically cluttered and reverberant environment.

Detección de sonidos nuevos. ¿Existen múltiples manifestaciones de un mismo fenómeno?

2008-01-01T00:00:00Z

Introducción. A pesar de que la detección de los sonidos nuevos es una tarea básica del sistema auditivo, todavía se desconocen en gran medida los procesos neuronales subyacentes. Desarrollo. Durante una estimulación repetitiva o una escena auditiva monótona, muchas neuronas auditivas muestran una reducción de su respuesta, debido a un proceso de adaptación. Este fenómeno, conocido como adaptación específica a los estímulos –stimulus specific adaptation (SSA)–, podría constituir el mecanismo neuronal de la detección de cambios en el entorno acústico. Estudios recientes han descrito la existencia de neuronas que muestran claramente SSA tanto en áreas auditivas corticales como subcorticales (como el colículo inferior) y que podrían formar parte del circuito neuronal de detección de cambios o eventos novedosos. La SSA, como se manifiesta en dichas neuronas, comparte numerosas características con el potencial de disparidad –mismatch negativity (MMN)–, un componente de los potenciales evocados relacionado con la detección de novedad contextual y que puede vincularse a ciertos procesos de memoria y focalización de la atención. A pesar de estos hallazgos, la relación entre SSA y MMN aún no está clara. Conclusiones. Las respuestas neuronales a cambios de sonidos pueden observarse de múltiples formas, desde el registro de neuronas hasta los potenciales evocados. Estas respuestas parecen representar distintas manifestaciones de un mismo proceso sensorial subyacente, que involucraría a una serie de áreas auditivas tanto corticales como subcorticales. La base neuronal de este proceso sensorial tendría su origen en alguna forma de adaptación neuronal.

Stimulus-Specific Adaptation in the Inferior Colliculus of the Anesthetized Rat

2009-01-01T00:00:00Z

[EN]To identify sounds as novel, there must be some neural representation of commonly occurring sounds. Stimulus-specific adaptation (SSA) is a reduction in neural response to a repeated sound. Previous studies using an oddball stimulus paradigm have shown that SSA occurs at the cortex, but this study demonstrates that neurons in the inferior colliculus (IC) also show strong SSA using this paradigm. The majority (66%) of IC neurons showed some degree of SSA. Approximately 18% of neurons showed near-complete SSA. Neurons with SSA were found throughout the IC. Responses of IC neurons were reduced mainly during the onset component of the response, and latency was shorter in response to the oddball stimulus than to the standard. Neurons with near-complete SSA were broadly tuned to frequency, suggesting a high degree of convergence. Thus, some of the mechanisms that may underlie novelty detection and behavioral habituation to common sounds are already well developed at the midbrain.

A Discontinuous Tonotopic Organization in the Inferior Colliculus of the Rat

2008-01-01T00:00:00Z

[EN]Audible frequencies of sound are encoded in a continuous manner along the length of the cochlea, and frequency is transmitted to the brain as a representation of place on the basilar membrane. The resulting tonotopic map has been assumed to be a continuous smooth progression from low to high frequency throughout the central auditory system. Here, physiological and anatomical data show that best frequency is represented in a discontinuous manner in the inferior colliculus, the major auditory structure of the midbrain. Multiunit maps demonstrate a distinct stepwise organization in the order of best frequency progression. Furthermore, independent data from single neurons show that best frequencies at octave intervals of approximately one-third are more prevalent than others. These data suggest that, in the inferior colliculus, there is a defined space of tissue devoted to a given frequency, and input within this frequency band may be pooled for higher-level processing.