Effect of locomotion on the auditory steady state response of head-fixed mice.

OBJECTIVES: Electroencephalographic (EEG) examinations of the auditory steady-state response (ASSR) can non-invasively probe cortical function to generate the gamma-band (40 Hz) oscillation, which is increasingly applied to the neurophysiological studies on the rodent models of psychiatric disorders. Though, it has been well established that the brain activities are significantly modulated by the behavioural state (such as locomotion), how the ASSR is affected remains unclear. METHODS: We investigated the effect of locomotion by recording local field potential (LFP) evoked by 40-Hz click-train from multiple brain areas: auditory cortex (AC), medial geniculate body (MGB), hippocampus (HP) and prefrontal cortex (PFC), in head-fixed mice free to run on a treadmill. Comparisons were conducted on the LFPs during spontaneous movement and stationary conditions. RESULTS: We found that in both the auditory (AC and MGB) and non-auditory areas (HP and PFC), locomotion reduced the initial negative deflection of LFP (early response during 0-100 ms from stimulus onset), and had no significant effect on the ASSR phase-locking to the late stimulus (100-500 ms). CONCLUSIONS: Our results suggest that different neural mechanisms contribute to the early response and ASSR, and the ASSR is a more robust biomarker to investigate the pathogenesis of neuropsychiatric disorders.

Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body.

BACKGROUND: Systemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus. METHODS: We implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB). RESULTS: We found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801. CONCLUSION: Our data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.

Emotional arousal modifies auditory steady state response in the auditory cortex and prefrontal cortex of rats.

Emotional state has been shown to influence cognitive performance. However, the influence of mood on auditory processing is not fully understood. The auditory steady state response (ASSR) is the entrainment of neural activities elicited by periodic auditory stimulation, which is commonly used to evaluate the sensory and cognitive functions of brain. It has been shown that ASSR at 40 Hz is impaired at some psychotic disorders, such as schizophrenia and bipolar disorder. The primary goal of this study is to investigate the effect of emotional arousal on ASSR. To this end, we performed simultaneous recordings of local field potential (LFP) in response to 40 Hz click-train stimuli in the primary auditory cortex (A1) and medial prefront cortex (mPFC) of rats. During the electrophysiological recording, a negative mood was induced by means of the foot shocks occurred randomly in the inter-stimulus intervals. We found that both the power and phase-locking of ASSR in A1 were significantly increased under arousal condition, and phase-locking of ASSR in mPFC was also increased. The enhanced ASSRs were accompanied by an increase in coherence between A1 and mPFC. Our results suggest that A1-to-mPFC information transfer is enhanced under arousal state and the functional connectivity between mPFC and A1 may contribute to the emotional modulation of auditory process.

Auditory steady-state responses in primary and non-primary regions of the auditory cortex in neonatal ventral hippocampal lesion rats.

Auditory steady-state responses (ASSRs) represent the electrophysiological activity of the auditory nervous system in response to a periodic acoustic stimulus. Spectrogram analysis can reveal the frequency and phase information entrained in ASSRs. Clinically, the ASSR is used to detect abnormalities in electroencephalographs obtained from schizophrenia patients, who show reduced power and phase locking of ASSRs. The neonatal ventral hippocampal lesion (NVHL) rat is a widely used model to investigate the neurodevelopmental mechanisms of schizophrenia. It has been established that NVHL rats exhibit several schizophrenia-like behavioral and molecular abnormalities. However, no clear abnormalities in ASSRs have been reported to date. The present study compared ASSRs of adult NVHL and sham-operated rats. We inserted microelectrodes into the primary auditory cortex (A1) or posterior auditory field (PAF) and recorded the local field potential (LFP) in response to 40- and 80-Hz click train stimuli. Spectrogram analysis was performed to obtain the mean trial power (MTP) and phase-locking factor (PLF) of the click train-evoked LFPs. We found that in the control animals, A1 showed a stronger MTP and PLF of ASSR than PAF, and NVHL operation mainly impaired the ASSR in PAF. Analysis of spike activity also indicated that NVHL operation extended the duration of tone-evoked responses in PAF neurons. Our results reveal, for the first time, that NVHL may distinctly influence the neural activities of primary and non-primary fields of the auditory cortex.