Differential Modulation Of The Auditory Steady State Response And Inhibitory Gating By Chloral Hydrate Anesthesia

Objective: Auditory steady-state response(ASSR)is an electroencephalographic(EEG)signal that is synchronous with the stimulus frequency when the auditory neurons in the brain are stimulated periodically by sound.The power(magnitude)and phase locking ability(phase consistency across trials)of the ASSR can reflect the functional integrity of the neural circuits that support synchronization across frequencies.EEG measurement of ASSR,particularly in the gamma frequency range(30-80 Hz),has been commonly used in the clinical examination of mental illness and in neuropharmacological experiments in animal models.Inhibitory gating(IG)is experimentally characterized by a reduced responsiveness to redundant stimuli.IG as an important regulatory mechanism of biological auditory function,can effectively prevent excessive input of sound information from damaging the limited information processing ability of the brain.Examination of IG may reveal some dysfunctions of brain.Similarly,many mental diseases such as schizophrenia,obsessive-compulsive neurosis,post-traumatic stress disorder and Alzheimer disease have been found to have obvious abnormalities in IG function.In some clinic examinations and animal experiments,general anesthesia is necessary to conduct electrophysiological recordings.However,the effects of anesthesia on ASSR and IG remain unclear.For this reason,we recorded local field potentials though electrodes implanted in different brain areas of rats: the auditory cortex(AC),hippocampus(HC),amygdala(AMY),and prefrontal cortex(PFC),and compared the characteristics of ASSR and IG under anesthetized and conscious conditions.Methods: 1.Animals: adult male Wistar rats weighing 250-300g(8-10 weeks old)were used for the experiments.2.Surgical preparation: The animal was anesthetized by an intraperitoneal injection.Microelectrodes were implanted in AC,HP,AMY and PFC and fixed with dental cement and isolated from the external environment.3.Auditory stimulus: ASSR and IG were measured by click-train and sound pairs respectively.Sound stimuli were generated by MATLAB software,and the frequency and intensity of sound stimulation were corrected by 1/2-inch condenser microphone.The waveform of each click was a rectangular pulse of a 0.2-ms duration,which repeated at a rate of 40 cycles/s and continued for a 0.5-s duration.In each session,the click-trains were presented 120 times with inter-train-intervals of 2-4 s.After the recording of ASSR,120 pairs of sounds were presented to the rats to evaluate IG.The sound pairs consisted of two 80-ms sounds of white noise(5-ms rising/falling time),presented at a fixed interval of 500 ms.The first sound in a sound pair was identified as the conditioning sound(C)and the second one was called the testing sound(T).There was an 8-10-s interval between the pairs of sounds.4.Record procedure: Electrophysiological recording was conducted in an electrically shielded,soundproof box.First,we recorded the LFPs evoked by click-trains and sound pairs when the rats were free(conscious condition).The recording session lasted about 30 min.Then,the rats were anesthetized with chloral hydrate(330-350 mg/kg,5%,i.p.).Twenty minutes later,when the rats were under general anesthesia indicated by the disappearance of nociceptive reflex(anesthetized condition),the LFPs evoked by click-trains and sound pairs were recorded again.The recording procedure was repeated 2-4 times on each rat with an interval of at least 3 days.5.Analysis of LFP: The microwire output was delivered to a multi-channel preamplifier,then to a digital signal processing module(RZ-2;TDT).The waveforms of the field potentials were obtained by applying a bandpass filter(1-300 Hz).The field potentials were imported into Matlab for further analysis.Results: We found that ASSR signals were the strongest in the AC,and decreased sequentially in the HP,AMY,and PFC.Chloral hydrate anesthesia significantly reduced the power and phase-locking of ASSR in the AC,HP,and AMY.In contrast,the extent of IG in the AC was weakest and it increased sequentially in the HP,AMY,and PFC.Anesthesia had less effect on the extent of IG.Conclusion: Our results suggest that ASSR and IG may originate from different neural circuits and that IG is more resistant to general anesthesia and therefore better suited to examining the functioning of non-auditory brain regions.