An in-vivo intracellular study of auditory thalamic neurons

Abstract

The present study investigates the neuronal mechanism of the corticofugal modulation on the auditory thalamus, which transmits auditory information from the periphery to the cortex. In this study, the intrinsic electrophysiological properties and the auditory responses of the neurons in the medial geniculate body (MGB) were investigated through in-vivo intracellular recording from pentobarbital anesthetized guinea pigs, while the auditory cortex was electrically activated. The non-acoustically-driven firing rate was 45.8 +- 23.3 Hz (mean +- SD, n=8) at membrane potentials of -45 mV, 30.6 +-19.4 Hz (n=14) at -50 mV, 18.0 +- 12.9 Hz (n=14) at -55 mV, and significantly decreased to 5.7 +- 7.4 Hz at -60 mV, and to 0.7 +- 1.5 Hz (n=10) at -65 mV (ANOVA, p<0.001). The discharge rate was calculated in the absence of acoustic stimuli over varied membrane potentials which were changed by intracellular injection of current or through automatic drifting. The maximum non-acoustically-driven rate was 160Hz. The auditory responsiveness of the MGB neurons was examined at membrane potentials over a range of -45 mV to -75 mV: the higher the membrane potential, the greater the responsiveness, and vice versa. For those neurons showed an excitatory postsynaptic potential (EPSP) or spikes on the EPSP to the noise burst stimulus, the amplitude of the EPSP decreased as the membrane potential was hyperpolarized. For the neurons showed an inhibitory postsynaptic potential (IPSP), or a spike followed by an IPSP to the noise-burst stimulus, the amplitude of the IPSP decreased when the membrane potential was hyperpolarized. A putative non-low-threshold calcium spike (non-LTS) burst was observed in the present study. It showed significantly longer inter-spike intervals (11.6 +- 6.0 ms, p<0.001, t-test) than those associated with the putative low-threshold calcium spike (LTS) bursts (6.7 +- 2.4 ms, p<0.001, t-test). Of 52 neurons responsive to sound, 29 showed excitatory auditory responses to acoustic stimuli. Ten of them showed burst-like responses to auditory stimuli, with excitatory postsynaptic potentials (EPSPs) exhibiting a mean amplitude and duration of 13.2+/-10.2 mV (range: 4-40 mv) and 184.0+/-126.6 ms (range: 20-420 ms), respectively. Fourteen showed a phasic response to an acoustic stimulus, with a mean amplitude and duration of the EPSPs of 10.2+/-5.5 mV and 158.6+/-95.4 ms. Five neurons showed a tonic response pattern. Fourteen neurons responded to auditory stimuli with an IPSP with a mean amplitude and duration of -10.1 +/-2.5 mV and 350.7+/-273.6 ms, respectively. Neurons with EPSP patterns tended to have a sharp-tuning curve, a low response threshold and a short response latency. The neurons with an IPSP pattern and a tonic response pattern tended to show a non-tuning characteristic, or a broad/double-peaked tuning curve with a higher threshold. OFF neurons responded to auditory stimuli of different durations with different latencies, or deviations of latencies, in addition to different spike numbers. Most OFF and ON-OFF neurons showed membrane oscillations with a frequency of about 5 Hz. The neurons changed their firing pattern to an LTS when the membrane potential was further hyperpolarized to < -75 mV. With an even lower membrane potential at < -85 mV, the neurons responded to the same noise-burst stimulus with an LTS burst. Of 92 neurons that received corticofugal modulation on the membrane potential, 38 neurons received potentiation and 50 neurons received hyperpolarization. Corticofugal potentiation of the membrane potential (amplitude: 8.6+-5.5 mV; duration: 125.5+-75.4 ms) facilitated the auditory responses and spontaneous firing of the MGB neurons. This hyperpolarization of -11.3+-4.9 mV in amplitude and 1023.0+-635.8 ms in duration suppressed or even totally diminished the auditory responses and spontaneous firing of the MGB neurons. Of 38 auditory excitatory neurons examined, 31 received corticofugal potentiation, four received corticofugal inhibition, and three received no effect. Of 33 auditory inhibitory neurons examined in the present study, 31 received corticofugal hyperpolarization on their membrane potential and two received no effect. The shapes of all of the EPSPs and IPSPs caused by the cortical stimulation were similar to those evoked by acoustic stimuli on each neuron. All of the nine auditory excitatory neurons that located in the lemniscal MGB received a corticofugal depolarization on their membrane potentials. All of the eight auditory inhibitory neurons located in the non-lemniscal MGB received a corticofugal inhibitory modulation effect. The present intracellular recording provides the first study of how the corticofugal projection gates the sensory information in the thalamus: that is spatially selective depolarization and hyperpolarization of the lemniscal and non-lemniscal MGB neurons. Present results also suggest a possible segregation of the excitatory and inhibitory neurons. The fact that a similar shape of postsynaptic potential caused by both ascending and descending inputs indicates a neuronal endogenous characteristic irrespective of the physical locations of the synapses. The dependence of the temporal structure of the spikes/spike bursts on the stimulus may provide insight into the temporal coding of sound information in the auditory system. The response patterns of the OFF neurons suggests that spike timing could be another parameter used by the thalamic neurons to encode the stimulus information. The finding that most OFF and ON-OFF neurons showed membrane oscillations strengthens the idea that membrane oscillations might be more dominant in the non-lemniscal MGB than in the lemniscal MGB.