Response properties and functional interactions of auditory thalamus and cortex in the guinea pig

Abstract

In the thesis study, we investigated the firing pattern and frequency tuning properties of medial geniculate body (MGB) neurons, corticofugal inhibition pathway to the auditory thalamus, and feed-forward modulation of the thalamocortical projections on the auditory cortex, through in-vivo intracellular recordings in anesthetized guinea pigs. Twenty-two of the 25 physiological characterized neurons were anatomically identified. Ten neurons were located in the the ventral division of the MGB (MGv) (seven in pars ovoidea (OV) and three in the pars lateralis (LV)). Eight were located in the dorsal division (MGd), and four in the medial division (MGm). OV neurons showed a uniform, phasic ON response with high frequency selectivity. Functionally, they are interpreted as relaying spectral information with high reliability. LV neurons exhibited various patterns: phasic, tonic and excitatory postsynaptic potentials (EPSP) with a spike train. These high magnitude EPSPs are proposed to convey temporal information of the auditory signals with more encoding power. MGd neurons had relatively low best frequencies while MGm neurons had high intensity threshold, broader frequency selectivity, and a tonic response pattern. Tonic firing is likely to impose a strong impact onto wide cortical area and amygdala. When hyperpolarized with current injection, low-threshold calcium spikes (LTS) were evoked in MGB neurons. Distinct change in these spike numbers was observed among MGv and MGd neurons as compared with MGm neurons, implying their differential roles. MGm neurons are more modulatory in nature, while the long lasting bursts of low-threshold calcium spikes observed in MGv and MGd neurons probably participate in propagating the sleep oscillations. Electrical stimulation of the auditory cortex (AC) causes both facilitatory and inhibitory effects on the MGB. To identify the corticofugal inhibitory pathway to the MGB, we assessed two potential circuits: 1) AC -> inferior colliculus (IC) -> MGB, i.e. corticocolliculothalamic pathway and 2) AC -> thalamic reticular nucleus (TRN) -> MGB, i.e., corticoreticulothalamic pathway. We compared the intracellular responses of 73 MGB neurons to electrical stimulation of the AC following bilateral ablation of the inferior colliculi or ipsilateral TRN lesions in anesthetized guinea pigs. Cortical stimulation in the control group could cause strong inhibitory effects in the non-lemniscal MGB neurons. The corticofugal inhibition remained effective after bilateral IC ablation, but it was minimized after ipsilateral TRN was lesioned with kainic acid. Synchronized TRN neuronal activity and MGB inhibitory postsynaptic potentials (IPSPs) were observed with multiple recordings. The results suggest that corticofugal inhibition traverses the corticoreticulothalamic pathway, indicating that the colliculi-geniculate inhibitory pathway is probably only for feedforward inhibition. The responses of 42 auditory cortical neurons to electrical stimulation of the MGB and auditory stimulus were recorded through intracellular recordings. A parallel array of stimulating electrodes was implanted into the MGB targeting the medial and ventral divisions. The stimulating sites in the MGB were confirmed by electrical lesions, and the recorded neurons were labeled with Neurobiotin after physiological recordings. Of the 42 AC neurons examined with thalamic electrical stimulation, 23 showed membrane excitation, 12 inhibition and the others displayed no effect. Stimulation of the MGv evoked mainly excitatory output in pyramidal neurons from layers II to V, while stimulation of the MGm triggered mainly inhibition and even changed oscillation rhythms of auditory cortical neurons. The activation of MGm might have both and facilitatory and inhibitory modulations on auditory cortex, even the global state of cortical networks. Further investigation is needed to explore the possible thalamocortical and intracortical mechanisms of such modulation.