Abstract
Auditory steady-state responses (ASSRs) are states in which the electrical activity of the brain reacts steadily to repeated auditory stimuli. They are known to be useful for testing the functional integrity of neural circuits in the cortex, as well as for their capacity to generate synchronous activity in both human and animal models. Furthermore, abnormal gamma oscillations on ASSR are typically observed in patients with schizophrenia (SZ). Changes in neural synchrony may reflect aberrations in cortical gamma-aminobutyric acid (GABA) neurotransmission. However, GABA’s impact and effects related to ASSR are still unclear. Here, we examined the effect of a GABAa receptor antagonist, (+)-bicuculline, on ASSR in free-moving rats. (+)-Bicuculline (1, 2 and 4 mg/kg, sc) markedly and dose-dependently reduced ASSR signals, consistent with current hypotheses. In particular, (+)-bicuculline significantly reduced event-related spectral perturbations (ERSPs) at 2 and 4 mg/kg between 10 and 30 minutes post-dose. Further, bicuculline (2 and 4 mg/kg) significantly and dose-dependently increased baseline gamma power. Furthermore, the occurrence of convulsions was consistent with the drug’s pharmacokinetics. For example, high doses of (+)-bicuculline such as those greater than 880 ng/g in the brain induced convulsion. Additionally, time-dependent changes in ERSP with (+)-bicuculline were observed in accordance with drug concentration. This study partially unraveled the contribution of GABAa receptor signals to the generation of ASSR.
Highlights
Auditory steady-state response (ASSR) measures the intrinsic ability of auditory neuronal ensembles to entrain to rhythmically presented stimuli and can be used to test the functional integrity of neural circuits that support synchronization [1,2,3] across frequencies in both human and animal models
Given that the temporal cortex is thought to play an important role in the generation of ASSRs, these findings suggest a potential link between GABAa abnormalities and ASSR disturbances in SZ
event-related spectral perturbations (ERSPs) is defined as an event-related change in power relative to a pre-stimulus baseline, while inter-trial coherence (ITC) is defined as phase consistency across trials, and ranges between 0 and 1 [35]
Summary
Auditory steady-state response (ASSR) measures the intrinsic ability of auditory neuronal ensembles to entrain to rhythmically presented stimuli and can be used to test the functional integrity of neural circuits that support synchronization [1,2,3] across frequencies in both human and animal models. Effects of (+)-bicuculline on ASSR in free-moving rats study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors’ salaries and/or research materials. The potential role of the GABA neurotransmitter system in the generation and maintenance of synchronous oscillations [28] has led to increased focus on the system’s possible involvement in the pathophysiology of SZ [29,30,31], with some neurobiological alterations observed in SZ suggested to result from a compensatory response to restore inhibitory synaptic efficacy [26]. To evaluate the pharmacological effects of GABAa receptor antagonists, we examined the pharmacokinetics of bicuculline and its effects on convulsion
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