The Modulation Of The Thalamic Reticular Nucleus On The Auditory Steady-state Responses Of The Medial Geniculate Body And Auditory Cortex

Objective: Gamma band oscillation(GBO)damage in electroencephalogram(EEG)is related to many serious neuropsychiatric diseases(such as schizophrenia).Auditory steady-state response(ASSR)is a typical GBO signal.ASSR is a synchronous electrical response signal produced by auditory neurons to periodic sound stimulation.Clinically,EEG or magnetoencephalography is often used to detect ASSR to determine the integrity of brain sensory neuron circuits and provide reference for the diagnosis and treatment of neuropsychiatric diseases.But the potential generation and regulation loop of ASSR is still unclear.The Thalamic reticular nucleus(TRN)is located on the dorsolateral thalamus.It is the inhibitory hub that plays a key role in the transmission of information in the thalamus-cortex loop.If the TRN function is abnormal,it will inevitably cause dysfunction of the sensory nervous system.Recently,more and more electrophysiological and pharmacological studies have confirmed that TRN dysfunction may be related to auditory cognitive impairment in patients with schizophrenia.To study the modulation of TRN neuronal activity on ASSR in thalamus-cortex,we used the method of recording local field potential(LFP)and single-unit activity(SUA)of mice thalamus-cortex combined with selective optogenetic stimulation.The optogenetic method is a bioengineering technology that has rapidly developed in the field of neuroscience in recent years.Its principle is that neurons expressing different light-sensitive ion channels will cause changes in the membrane potential on both sides of the cell membrane under different wavelengths of light stimulation.Here,to illustrate the correlation between TRN dysfunction and ASSR abnormalities,and provide new clues for fully understanding the formation mechanism and related pathological changes of ASSR,we investigate the effect of TRN on the ASSR in the medial geniculate body(MGB)and auditory cortex(AC),combining optogenetic stimulation and electrophysiological recording.Methods: 1.Animals: Select healthy adult transgenic mice aged 6-8 weeks,weighing18-25 g,strain background is C57BL/6(code: 014548,VGAT-Ch R2-EYFP,supplier:Jackson Laboratories).2.Operation: Under the state of mouse anesthesia,a fiber optic ferrule was implanted in the TRN of the mouse and fixed with dental cement.After one week of recovery,a single tungsten electrode(resistance 3-5 M?).3.Sound stimulus: Click train is a rectangular pulse with a duration of 0.2 ms and a frequency of 40 Hz for 0.5 s.The waveform of the sound stimulation is a digital signal generated by a self-made MATLAB program at a sampling rate of 100 k Hz,and converted to an analog signal through the D/A board,and then played through the speaker.In each recording,120 click-train stimuli were performed at random intervals of 2 to 4 s.4.Light stimulus: The stimulus light is generated by the laser and transmitted to the fiber ferrule implanted in the mouse skull through a customized fiber optic jumper.According to the experimental requirements,two modes of light stimulation were performed in a pseudo-random manner: a single 10 ms pulse and a continuous 1000 ms pulse.In the experiment to explore the effect of light-activated TRN on AC and MGB-induced ASSR,continuous 1000 ms pulse laser stimulation was used,and sound stimulation was given 250 ms after the start of light to ensure that TRN was in the excited state.5.Neuroelectrophysiological recording: In the shielded recording room,we record the LFP and SUA induced by the mouse MGB and AC under the conditions of simple sound stimulation,light stimulation TRN,and light stimulation TRN with sound stimulation.6.Data acquisition and analysis: The original EEG signal recorded by a single tungsten electrode is converted and amplified by the headstage,and then output to the recording device,and then the LFP and SUA are generated through the band-pass filter based on the fast Fourier transform.Use MATLAB to analyze the results of LFP and SUA.Results: The results of electrophysiological recordings showed that light stimulation induced LFP and SUA responses in MGB and AC.Under the condition that TRN was activated,we found that the LFP and SUA responses induced by 40 Hz click-train in MGB and AC are affected to varying degrees.Among them,an increase of the early auditory response and decrease of the later auditory response in AC.The Onset response of MGB did not change significantly,while the ASSR response was decreased.Conclusion: Our optogenetic and electrophysiological data indicate that over-activation of TRN neurons may lead to complex auditory EEG changes,increased early auditory evoked responses and decreased late auditory evoked responses.It can be seen that the decreasing of ASSR in patients with schizophrenia and other mental illnesses may be related to the hyperactivity of TRN neurons.Our results also provide an important reference for understanding how TRN neurons regulate the activities of the thalamic cortical network.