Stimulus-specific adaptation and deviance detection in the inferior colliculus

[EN] Deviancy detection in the continuous flow of sensory information into the central nervous system is of vital importance for animals. The task requires neuronal mechanisms that allow for an efficient representation of the environment by removing statistically redundant signals. Recently, the neuronal principles of auditory deviance detection have been approached by studying the phenomenon of stimulus-specific adaptation (SSA). SSA is a reduction in the responsiveness of a neuron to a common or repetitive sound while the neuron remains highly sensitive to rare sounds (Ulanovsky et al., 2003). This phenomenon could enhance the saliency of unexpected, deviant stimuli against a background of repetitive signals. SSA shares many similarities with the evoked potential known as the “mismatch negativity,” (MMN) and it has been linked to cognitive process such as auditory memory and scene analysis (Winkler et al., 2009) as well as to behavioral habituation (Netser et al., 2011). Neurons exhibiting SSA can be found at several levels of the auditory pathway, from the inferior colliculus (IC) up to the auditory cortex (AC). In this review, we offer an account of the state-of-the art of SSA studies in the IC with the aim of contributing to the growing interest in the single-neuron electrophysiology of auditory deviance detection. The dependence of neuronal SSA on various stimulus features, e.g., probability of the deviant stimulus and repetition rate, and the roles of the AC and inhibition in shaping SSA at the level of the IC are addressed

Cholinergic Modulation of Stimulus-Specific Adaptation in the Inferior Colliculus

[EN] Neural encoding of an ever-changing acoustic environment is a complex and demanding process that depends on modulation by neuro-active substances. Some neurons of the inferior colliculus (IC) exhibit “stimulus-specific adaptation” (SSA), i.e., a decrease in their response to a repetitive sound, but not to a rare one. Previous studies have demonstrated that acetylcholine (ACh) alters the frequency response areas of auditory neurons and therefore is important in the encoding of spectral information. Here, we address how microion-tophoretic application of ACh modulates SSA in the IC of the anesthetized rat. We found that ACh decreased SSA in IC eurons by increasing the response to the repetitive tone. This effect was mainly mediated by muscarinic receptors. The strength of the cholinergic modulation depended on the baseline SSA level, exerting its greatest effect on neurons with intermediate SSA responses across IC subdivisions. Our data demonstrate that the increased availability of ACh exerts transient functional changes in partially adapting IC neurons, enhancing the sensory encoding of the ongoing stimulation. This effect potentially contributes to the propagation of ascending sensory-evoked afferent activity through the thalamus en route to the cortex

Deviance detection in auditory subcortical structures: what can we learn from neurochemistry and neural connectivity?

[EN] A remarkable ability of animals that is critical for survival is to detect and respond to to unexpected stimuli in an ever-changing world. Auditory neurons that show stimulusspecific adaptation (SSA), i.e., a decrease in their response to frequently occurring stimuli while maintaining responsiveness when different stimuli are presented, might participate in the coding of deviance occurrence. Traditionally, deviance detection is measured by the mismatch negativity (MMN) potential in studies of evoked local field potentials.We present a review of the state-of-the-art of SSA in auditory subcortical nuclei, i.e., the inferior colliculus and medial geniculate body of the thalamus, and link the differential receptor distribution and neural connectivity of those regions in which extreme SSA has been found. Furthermore, we review both SSA and MMN-like responses in auditory and non-auditory areas that exhibit multimodal sensitivities that we suggest conform to a distributed network encoding for deviance detection. The understanding of the neurochemistry and response similarities across these different regions will contribute to a better understanding of the neural mechanism underlying deviance detection

Neuronal adaptation, novelty detection and regularity encoding in audition

The ability to detect unexpected stimuli in the acoustic environment and determine their behavioral relevance to plan an appropriate reaction is critical for survival. This perspective article brings together several viewpoints and discusses current advances in understanding the mechanisms the auditory system implements to extract relevant information from incoming inputs and to identify unexpected events. This extraordinary sensitivity relies on the capacity to codify acoustic regularities, and is based on encoding properties that are present as early as the auditory midbrain. We review state-of-the-art studies on the processing of stimulus changes using non-invasive methods to record the summed electrical potentials in humans, and those that examine single-neuron responses in animal models. Human data will be based on mismatch negativity (MMN) and enhanced middle latency responses (MLR). Animal data will be based on the activity of single neurons at the cortical and subcortical levels, relating selective responses to novel stimuli to the MMN and to stimulus-specific neural adaptation (SSA). Theoretical models of the neural mechanisms that could create SSA and novelty responses will also be discussed

Frequency discrimination and stimulus deviance in the inferior colliculus and cochlear nucleus

[EN] Auditory neurons that exhibit stimulus-specific adaptation (SSA) decrease their response to common tones while retaining responsiveness to rare ones. We recorded single-unit responses from the inferior colliculus (IC) where SSA is known to occur and we explored for the first time SSA in the cochlear nucleus (CN) of rats. We assessed an important functional outcome of SSA, the extent to which frequency discriminability depends on sensory context. For this purpose, pure tones were presented in an oddball sequence as standard (high probability of occurrence) or deviant (low probability of occurrence) stimuli. To study frequency discriminability under different probability contexts, we varied the probability of occurrence and the frequency separation between tones. The neuronal sensitivity was estimated in terms of spike-count probability using signal detection theory. We reproduced the finding that many neurons in the IC exhibited SSA, but we did not observe significant SSA in our CN sample. We concluded that strong SSA is not a ubiquitous phenomenon in the CN. As predicted, frequency discriminability was enhanced in IC when stimuli were presented in an oddball context, and this enhancement was correlated with the degree of SSA shown by the neurons. In contrast, frequency discrimination by CN neurons was independent of stimulus context. Our results demonstrated that SSA is not widespread along the entire auditory pathway, and suggest that SSA increases frequency discriminability of single neurons beyond that expected from their tuning curves

Differences in the strength of cortical and brainstem inputs to SSA and non-SSA neurons in the inferior colliculus

[EN] In an ever changing auditory scene, change detection is an ongoing task performed by the auditory brain. Neurons in the midbrain and auditory cortex that exhibit stimulus-specific adaptation (SSA) may contribute to this process. Those neurons adapt to frequent sounds while retaining their excitability to rare sounds. Here, we test whether neurons exhibiting SSA and those without are part of the same networks in the inferior colliculus (IC). We recorded the responses to frequent and rare sounds and then marked the sites of these neurons with a retrograde tracer to correlate the source of projections with the physiological response. SSA neurons were confined to the non-lemniscal subdivisions and exhibited broad receptive fields, while the non-SSA were confined to the central nucleus and displayed narrow receptive fields. SSA neurons receive strong inputs from auditory cortical areas and very poor or even absent projections from the brainstem nuclei. On the contrary, the major sources of inputs to the neurons that lacked SSA were from the brainstem nuclei. These findings demonstrate that auditory cortical inputs are biased in favor of IC synaptic domains that are populated by SSA neurons enabling them to compare top-down signals with incoming sensory information from lower areas

Archivo de conferencias y seminarios del Máster en Neurociencias‐INCyL

Memoria ID-188. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Stimulus-specific adaptation in the inferior colliculus: The role of excitatory, inhibitory and modulatory inputs

[EN] Patients suffering from pathologies such as schizophrenia, depression or dementia exhibit cognitive impairments, some of which can be reflected in event-related potential (ERP) measurements as the mismatch negativity (MMN). The MMN is one of the most commonly used ERPs and provides an elec-trophysiological index of auditory change or deviance detection. Moreover, MMN has been positioned as a potentially promising biomarker candidate for the diagnosis and prediction of the outcome of schizophrenia. Dysfunction of neural receptors has been linked to the etiopathology of schizophrenia or the induction of psychophysiological anomalies similar to those observed in schizophrenia. Stimulus-specific adaptation (SSA) is a neural mechanism that contributes to the upstream processing of auditory change detection. Auditory neurons that exhibit SSA specifically adapttheir response to repetitive sounds but maintain their excitability to respond to rare ones. Thus, by studying the role of neuronal receptors on SSA, we can contribute to detangle the cellular bases ofthe impairments in deviance processing occurring in mental pathologies. Here, we review the current knowledge on the effect of GABAA-mediated inhibition and themodulation of acetylcholine on SSAin the inferior colliculus, and we add unpublished original data obtained blocking glutamate receptors. We found that the blockade of GABAA and glutamate receptors mediates an overall increase or decrease of the neural response, respectively, while acetylcholine affects only the response to the repetitive sounds. These results demonstrate that GABAergic, glutamatergic and cholinergic receptors play different and complementary roles on shaping SSA

Acetylcholine modulates the precision of prediction error in the auditory cortex

A fundamental property of sensory systems is their ability to detect novel stimuli in the ambient environment. The auditory brain contains neurons that decrease their response to repetitive sounds but increase their firing rate to novel or deviant stimuli; the difference between both responses is known as stimulus-specific adaptation or neuronal mismatch (nMM). Here, we tested the effect of microiontophoretic applications of ACh on the neuronal responses in the auditory cortex (AC) of anesthetized rats during an auditory oddball paradigm, including cascade controls. Results indicate that ACh modulates the nMM, affecting prediction error responses but not repetition suppression, and this effect is manifested predominantly in infragranular cortical layers. The differential effect of ACh on responses to standards, relative to deviants (in terms of averages and variances), was consistent with the representational sharpening that accompanies an increase in the precision of prediction errors. These findings suggest that ACh plays an important role in modulating prediction error signaling in the AC and gating the access of these signals to higher cognitive levels