| Summary: | 博士 === 國立臺灣大學 === 動物學研究所 === 99 === Thalamus is regarded as the gateway for sensory information relay from periphery to higher cortical areas, and has been suggested to play pivotal roles in state-dependent information processing and several different types of neurological disorders. Relay neurons in the ventrobasal nucleus (VBN) of the thalamus transmit somatosensory information to the cerebral cortex and receive sensory and cortical (feedback) synaptic inputs via, respectively, medial lemniscal (ML) and corticothalamic (CT) fibres. Despite an invaluable model for studying central processes of sensation and perception, this system has not been well characterized in terms of basic details of the excitatory synaptic transmission and plasticity. With more functional relevance, changes of the synaptic transmission, especially in response to physiological patterned activities, have critical implications for the computation of the thalamo-cortico-thalamic network, but this aspect is rarely studied. For example, the duality of spiking modes, burst and continuous, was thought to underlie state dependence of thalamic information transfer, but the impact of different firing patterns on synaptic weight is not explored.
Our work applies standard whole-cell patch-clamp electrophysiology and cellular histochemistry to study the fast excitatory synaptic transmission and plasticity of relay neurons in the ventrobasal nucleus of rat thalamus in a systematic and comparative manner. CT and ML synapses had distinct properties in terms of stimulus-response relationships and short-term plasticity: CT excitatory postsynaptic current (EPSC) had linear input-output relationship and paired-pulse facilitation, while ML EPSC all-or-none and paired-pulse depression. More interestingly, the compositions of ionotropic glutamate receptors differed. CT synapses showed higher NMDAR / non-NMDAR peak current ratio than ML synapses, and preferentially expressed calcium-permeable AMPA receptors (CaP-AMPARs). Activation of these receptors has been widely implicated in the induction and / or expression of synaptic plasticity, which motivated the comparison of synaptic plasticity between these two synapses. NMDAR-dependent long-term potentiation (LTP) and L-type voltage-gated calcium channel(VGCC)-dependent long-term depression (LTD) were readily induced at CT synapses, but not ML synapses, under the induction protocols tested. In addition, CT synaptic strength could be modulated in response to pre- and postsynaptic activities in an integrative manner while multiple induction conditions were met concurrently. Efforts were then made to elucidate the role of ionotropic glutamate receptors in long-term plasticity of CT synapses by experimental and analytical approaches. We found that activation of CaP-AMPARs and NMDARs contributed to neither induction nor expression of LTD at CT synapses, and evidence further suggested that the expression of LTD mainly involves presynaptic modification.
In order to get insights into the physiological conditions for induction of synaptic plasticity, several protocols involving different spiking and pairing patterns were tested under current-clamp recording. Intriguingly, LTD was induced at CT synapses in response to repetitive continuous spiking, rather than burst spiking, of VBN relay neuron. Furthermore, we showed that LTP at CT synapses could be induced by repetitive, low-frequency pairing of CT EPSP with burst spiking of relay neuron, but not by pairing of CT EPSP with high-frequency spiking (without LTS) which mimicked the fast Na+ action potentials riding on the LTS of natural burst spiking, suggesting a critical role of T-type VGCCs in the induction of STDP at CT synapses.
In light of our discovery, I propose a working model of dynamic thalamic information relay, and generate testable ideas for future research. Taken together, this study unveils the fundamental functional differences between sensory and cortical inputs onto thalamic relay neurons, and shows that the strength of corticothalamic pathway is preferentially subjected to use-dependent modifications, which can be a cellular substrate for dynamic regulation of thalamic information relay, and therefore instrumental to our in-depth interpretation and understanding of the ongoing in-vivo sensory processes within the thalamocortical system at synaptic and cellular levels.
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