Modulation of stimulus‐specific adaptation by GABA_A receptor activation or blockade in the medial geniculate body of the anaesthetized rat

Abstract

Key points• Neurons in the medial geniculate body (MGB), the auditory thalamus, give stronger responses to rare sounds than to repetitive sounds, a phenomenon referred to as stimulus-specific adaptation (SSA).• The present study sought to elucidate how the inhibitory thalamic circuitry acting at GABA A receptors affects the generation and/or modulation of SSA from recordings of single unit responses from MGB. Microiontophoretic application of GABAergic agonists selectively increased SSA indices, whereas application of antagonists selectively reduced SSA values.• We found that GABA A -mediated inhibition did not generate the SSA response but regulated the magnitude of SSA sensitivity in a gain control manner.• These findings advance our understanding of the role of inhibition in coding deviance detection in the MGB.Abstract Stimulus-specific adaptation (SSA), which describes adaptation to repeated sounds concurrent with the maintenance of responsiveness to uncommon ones, may be an important neuronal mechanism for the detection of and attendance to rare stimuli or for the detection of deviance. It is well known that GABAergic neurotransmission regulates several different response properties in central auditory system neurons and that GABA is the major inhibitory neurotransmitter acting in the medial geniculate body (MGB). The mechanisms underlying SSA are still poorly understood; therefore, the primary aim of the present study was to examine what role, if any, MGB GABAergic circuits play in the generation and/or modulation of SSA. Microiontophoretic activation of GABA A receptors (GABA A Rs) with GABA or with the selective GABA A R agonist gaboxadol significantly increased SSA (computed with the common SSA index, CSI) by decreasing responses to common stimuli while having a lesser effect on responses to novel stimuli. In contrast, GABA A R blockade using gabazine resulted in a significant decrease in SSA. In all cases, decreases in the CSI during gabazine application were accompanied by an increase in firing rate to the stimulus paradigm. The present findings, in conjunction with those of previous studies, suggest that GABA A -mediated inhibition does not generate the SSA response, but can regulate the level of SSA sensitivity in a gain control manner. The existence of successive hierarchical levels of processing through the auditory system suggests that the GABAergic circuits act to enhance mechanisms to reduce redundant information.

Specific Early and Late Oddball-Evoked Responses in Excitatory and Inhibitory Neurons of Mouse Auditory Cortex

“…3). Although subcortical SSA has been reported primarily in the nonlemniscal part of inferior colliculus Ayala and Malmierca, 2012) and the medial geniculate body of thalamus (Anderson et al, 2009;Antunes et al, 2010), the prominent SSA seen in the lemniscal A1 in our study and previous studies (Ulanovsky et al, 2003;Hershenhoren et al, 2014) indicates de novo generation or amplification of SSA in cortical circuitry (Nelken, 2014). Two mechanisms may contribute to the recovered early responses evoked by oddballs.…”

“…For example, in primary auditory cortex (A1), stimulus-specific adapta-tion (SSA) has been reported as the decrease in neuronal response to repeating "standard" tones, which does however not fully generalize to a rare and irregular "oddball" tone (Nelken, 2014;Pérez-González and Malmierca, 2014). In extracellular recording experiments, SSA occurring tens of milliseconds after tone onset has been identified in A1 of various mammalian species (Ulanovsky et al, 2003;von der Behrens et al, 2009;Taaseh et al, 2011;Fishman and Steinschneider, 2012), as well as subcortically in inferior colliculus Duque et al, 2012) and auditory thalamus (Anderson et al, 2009). Similarly, a prominent electroencephalographic (EEG) signal known as "mismatch negativity" (MMN), typically peaking ϳ100 -250 ms after stimulus onset, is evoked by deviant tones in the human and animal brain.…”

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

“…11D). The delicate modulation of ACh that selectively increases the evoked response to the standard sound without affecting the timing of the neural response contrasts with the gain control exerted by GABA A -mediated inhibition in IC and MGB neurons (Duque, Malmierca, & Caspary, 2014), as well as by glutamatergic excitation. From these results, we can conclude that glutamatergic excitation, ACh and GABA A -mediated inhibition produce different effects on the adaptation dynamics.…”

GABAergic inhibition shapes SAM responses in rat auditory thalamus

“…The balancing barrel was filled with potassium acetate (KAc, 2 M), with remaining barrels filled with γ-Aminobutyric acid (GABA, 500 mM, pH = 4.0, Sigma-Aldrich, St. Louis, MO), gabazine (SR-95531) (GBZ, 10 mM, Sigma-Aldrich, St. Louis, MO) and AP5 (100 mM, pH = 7.4). Retaining currents were set at −15 nA as previous studies (Cai et al, 2013, Duque et al, 2013). The KAc filled balancing barrel neutralizes all currents by passing current equal and opposite currents being used.…”