Heterosynaptic Neuroplasticity of the Ascending Inputs in the Auditory Thalamus by Corticothalamic Modulation

Project: Research

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Reciprocal neural circuits linking the thalamus and cortex has been proposed to contribute to sensory processing and cognition. Cortical feedback to the thalamus has been suggested as a gain-control feature modulating the ascending transmission of sensory information. In the auditory system, corticofugal projections to the medial geniculate body (MGB) are tonotopically organized. Short-term and homeostatic corticothalamic neuroplasticities have been demonstrated in different systems. In a recent project, we successfully induced long-term potentiation (LTP) of the corticothalamic pathway after high-frequency stimulation (HFS) of the auditory cortex under in-vivo preparation. And the corticothalamic LTP was cholecystokinin (CCK) dependent. Preliminary results show that the corticofugal long-term neuroplasticity may happen heterosynaptically, i.e., HFS of the corticothalamic pathway induces LTP of tectothalamic pathway in the auditory system. In this proposed project, we aim to explore the mechanism underlying such long-term corticofugal modulation on ascending auditory information. We hypothesize that 1) there is a time window for long-term corticothalamic neuroplasticity during the development of mice, and 2) corticothalamic heterosynaptic plasticity is specific to the simultaneously activated ascending frequency pathway and improves the sensitivity toward that frequency. To test the hypotheses, we will examine the HFS-induced corticothalamic LTP in in-vivo on mice at different postnatal days to determine the onset and offset of the critical period. We will examine the heterosynaptic plasticity of the tectothalamic projections before and after the high-frequency optogenetic stimulus (HFOS) in the corticothalamic pathway. We further test the improvement of auditory discrimination ability after pure tone exposure pairing with the corticothalamic HFOS. Finally, we will explore the long-term corticofugal modulation using pre-pulse inhibition (PPI) of acoustic startle responses. We select two tones as auditory probe stimulation and measure the PPI of both tones to the startle response. After the pairing protocol, we expect the responding sound threshold to be lower for the paired tone, not for the unpaired tone. The unveiling of the time window of corticofugal plasticity has a clinical implication on early intervention programs used for children with hearing loss. It may serve as an essential reference for the cochlear implantation period, providing better treatment for patients with hearing impairments. The corticothalamic heterosynaptic neuroplasticity may lead to more studies in rewiring the ascending inputs to the thalamus for brain disorders such as tinnitus. 


Project number9043301
Grant typeGRF
StatusNot started
Effective start/end date1/01/23 → …