Thalamic Activation Modulates the Responses of Neurons in Rat Primary Auditory Cortex: An In Vivo Intracellular Recording Study

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing

Electrical stimuli in the MGBv modulated the auditory responses of AI neurons.

<p>A) High- and low-frequency train electrical stimulation in the MGBv induced different effects in the auditory responses of AI neurons. The amplitudes of the sound-evoked EPSPs increased when the frequency of the train stimuli was 10 Hz and the electric current strength was 200 µA. In contrast, the 100 Hz train electrical stimulation of the MGBv with the same current strength depressed the sound-evoked responses of AI neurons. <b>B</b>) The statistical histogram of the average amplitudes of the EPSPs induced by sound after electric stimulation of the MGBv. The data were from the same recordings as in (A). The amplitudes of the noise-evoked EPSPs from the 10 Hz group were higher than those of both the 100 Hz group and the control group. The amplitudes in the 100 Hz group were also lower than those in the control group. (*<i>P</i><0.05, **<i>P</i><0.01, Error bars, S.D.).</p

Schematic diagram of experimental configuration and procedure.

<p><b>A</b>) A tungsten electrode was impelled into the right MGBv to record the electrophysiological characteristics of the neurons in the MGB and verify that the stimulating site was fully within the MGBv. Next, the tungsten electrode was fixed in place to stimulate the MGBv. After that, a sharp glass electrode was impelled to record the intracellular signals of AI neurons. <b>B</b>) Stimulation models. One sample consisted of an electrical stimulus of the MGBv paired with a testing white noise. The intervals between the onsets of the two stimuli were varied from 500 ms to 3000 ms. The intervals between the different samples were longer than 5 s.</p

Auditory responses of a cortical neuron after the electrical stimulation of the MGB.

<p><b>A</b>) The wave form of spontaneous discharge and oscillation of a single neuron in AI. The frequency of spontaneous discharge was approximately 3 Hz, and the frequency of spontaneous oscillation was approximately 2 Hz. Its RMP was −73 mV, and the baseline of the membrane potential in this neuron was flat and stable. <b>B</b>) Auditory neuronal responses to repeated noise-burst stimuli. The discharge rate and frequency of membrane oscillation of the neuron all increased. <b>C</b>) Noise-evoked responses of the same AI neuron after the electrical stimulation of the MGBv. The frequency and intensity of train stimulation of the MGBv were 10 Hz and 150 µA, respectively. The left inset figure is the five superimposed traces of the responses of the AI neuron in (B) to the paired stimuli, and the right inset figure is the amplified traces of the left inset figure. It was the clear waveforms of the paired sound-evoked responses in the AI neuron after train stimulation of the MGBv. The waveforms shown as follows were all of this type.</p

Different responses of AI neurons at varied intervals between paired stimuli.

<p><b>A</b>) Five superimposed waveforms of the paired sound-evoked responses in AI neurons after train stimulation of the MGBv at incremental intervals between the paired stimuli. <b>B</b>) The statistical broken line chart of the average amplitude of the EPSPs in (A). When the frequency of the train stimuli was 10 Hz, the amplitudes of the sound-evoked EPSPs significantly increased immediately after the train stimulation of the MGBv (compared with the control level), and then decreased to a level lower than the control group when the stimulus interval was extended to 700 ms. Finally, when the stimulus interval was approximately 800 ms, it reached the average amplitude of sound-evoked EPSPs without train stimulation (that is, the level of the control group). In contrast, the 100 Hz train electrical stimulation of the MGBv at first decreased the amplitudes of sound-evoked EPSPs in AI neurons to a significant low level. The amplitudes of the EPSPs then increased to the level of control group. The amplitudes of the EPSPs in both the high- and low-frequency group reached the control level and stabilized at the plateau when the stimulus interval was longer than 800 ms. (*<i>P</i><0.05, **<i>P</i><0.01).</p

Different responses of AI neurons at varied frequencies and intervals of train stimuli.

<p><b>A</b>) Five superimposed traces of the sound-evoked responses in AI neurons after train stimulation of the MGBv at incremental frequencies of electrical stimulation and intervals between the paired stimuli. <b>B</b>) The statistical broken line chart of the average amplitudes of the EPSPs in (A). When the stimulus intervals were shorter than 700 ms, the changing tendencies of the different groups of varied stimulus intervals were approximately the same. They all exhibited consistent effects. The amplitudes of the sound-evoked EPSPs of AI neurons increased to higher than those of the control group when the train stimulus frequency of the MGBv was 10 Hz. When the frequencies of the electrical stimuli increased to high levels, including 50 Hz, 100 Hz and 150 Hz, the amplitudes of the EPSPs all decreased to lower than those of the control group. In particular, when the frequency was 50 Hz, the amplitudes of the EPSPs were significantly lower than those of the control group, and might even be close to zero. (*<i>P</i><0.05).</p

Confirmation of the location of the MGBv.

<p><b>A</b>) The receptive field of the recorded MGBv neurons. This field had a typical “V" shape that was in concordance with the representative receptive field of the neurons in the MGBv, which further confirmed the location of the MGBv. The best frequency of this single unit was approximately 13 kHz, and its minimum threshold was approximately 7 dB SPL. <b>B</b>) The anatomical location of the site of electrical stimulation. A micrograph of the coronal section of the right brain compared with the atlas at 5.5 mm posterior to the bregma. A lesion site enwrapped with a thick layer of injured neurons could be observed at the corresponding position of the MGBv according to the atlas, whose boundary was sleek and clear-cut. Inset, position of the section in the rat brain. CTX, cortex; MGBv, ventral portion of the medial geniculate body; Hip, hippocampus; CA1, CA2, CA3, fields CA1, CA2, and CA3 of the hippocampus; SNR, reticular part of the substantia nigra; SC, superior colliculus; DpG, deep gray layer of the superior colliculus.</p