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

Abstract

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 electrophysiological 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 adapt their 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 of the impairments in deviance processing occurring in mental pathologies. Here, we review the current knowledge on the effect of GABAA-mediated inhibition and the modulation of acetylcholine on SSA in the inferior colliculus, and we add unpublished original data obtained blocking glutamate receptors.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.

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

“…Increased E/I ratio is also reflected in the power spectra of spontaneous, oscillatory brain activity, particularly in high-frequency (gamma; 30–90Hz) bands((42), but see(43)). Neural disinhibition yields higher baseline activity across frequency bands and failure of event-related activity to modulate, adapt, or be suppressed over repeated events(44). Pharmacological models altering GABAergic and glutamatergic neurotransmission confirm excitatory and inhibitory signaling contribute significantly to high-frequency oscillations(45,46).…”

Synaptic interactions and inhibitory regulation in auditory cortex

“…The purpose of this review is to promote an understanding of the relationship between the MMN and schizophrenia by highlighting some of the basic cortical circuitry, synaptic interactions and neuronal subtypes that contribute to auditory processing. Additional links between basic neurophysiology and clinical use of the MMN are found in recent reviews of stimulus-specific adaptation (SSA), which likely contributes to the production of the MMN (Ayala, et al, 2015; Grimm, et al, 2015). An important conclusion of this review is that while a role for NMDA receptors in generating the MMN has been posited for some time, to concentrate solely on NMDA receptors may be too narrow of an approach.…”

“…While the mechanisms and functions of the MMN are being actively investigated, as discussed in companion reviews, a key finding is that the MMN is reduced by drugs that block glutamate receptors of the N -methyl-D-aspartate (NMDA) subtype (Catts, Lai, Weickert, Weickert, & Catts, 2015; Harms, 2015; Javitt, 2000; Javitt, Steinschneider, Schroeder, & Arezzo, 1996; Todd et al, 2014; Wacongne, 2015). The neural origins of the MMN within the auditory system also are addressed by reviews of stimulus-specific adaptation (SSA), whereby the auditory system responds more strongly to rare or novel stimuli than to common stimuli (Ayala, Perez-Gonzalez, & Malmierca, 2015; Grimm, Escera, & Nelken, 2015). In turn, this review will focus on even more fundamental processes in auditory cortex, specifically, how excitatory postsynaptic potentials (EPSPs), including those mediated by NMDA receptors, are regulated by synaptic inhibition (inhibitory postsynaptic potentials, IPSPs) in auditory cortex.…”

Spatial Processing Is Frequency Specific in Auditory Cortex But Not in the Midbrain

“…Both our data and SSA can be explained by a convergence of information with either comparisons across the ears or adaptation occurring independently within separate frequency-specific channels (Mill et al, 2011, Duque et al, 2016). Manipulations of GABAergic, glutamatergic, and cholinergic synapses (Ayala et al, 2016) and descending control from AC (Malmierca et al, 2015) also suggest that SSA in IC is influenced by changes in overall excitability or adaptation rather than being crucially dependent on them, again supporting the model of constructive convergence. Other similarities between the phenomena include larger effects with increased frequency difference (Ulanovsky et al, 2003; cf.…”