| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 100 === In most mammals, synchronous oscillation in thalamocortical network is particularly found in the NREM (non-rapid eye movement) sleep state, in which the thalamus shows characteristic burst firing activity, rather than in the wakefulness and REM (rapid eye movement) sleep states. Previous studies have shown that monoaminergic and cholinergic neuromodulators from the brainstem depolarize the membrane and consequently alter the firing pattern of thalamic relay neurons in a sleep/wakefulness state-dependent manner. However, it is less understood whether and how the state-dependent modulators from the brainstem could also modulate the timing and the extent of synaptic inputs into relay neurons, another important determinant of postsynaptic firing activity. On the other hand, local chemical regulators such as adenosine that accumulates with prolonged wakefulness may also play a role. In this study, we examined the possible syanpse-modulatory effects with individual and combined neuromodulators mimicking different sleep-wakefulness states at the thalamic retinogeniculate synapse, which transmits retinal visual information to thalamic relay neurons. We found that purinergic or aminergic agonists when applied separately would decrease both strength and paried-pulse depression of retinogeniculate synaptic transmission. In contrast, cholinergic agonists do not alter basic synaptic strength but selectively increase the second synaptic current amplitude upon paired presynaptic stimulation, resulting in an apparent decrease of paired-pulse depression. Moreover, short-term synaptic plasticity is similarly and largely eliminated by application of combined neuromodulators mimicking the wakefulness and REM sleep states (i.e. application of aminergic plus cholinergic agonists and adenosine plus cholinergic agonists, respectively). On the other hand, application of neuromodulators (e.g. adenosine plus aminergic agonists) mimicking the NREM sleep states leads to decreased synaptic strength and transformation of short-term synaptic plasticity from depression to facilitation. The transformation suggests that multiple mechanisms regarding different forms of short-term plasticity could be present in one synapse and that the synaptic transmission is basically inhibited but may still be feasible when presynaptic activity frequency is high enough in the NREM state. We conclude that neuromodulation of not only thalamic neuronal membrane properties but also synaptic transmission should play an important role in the regulation of sleep state-dependent activity in the thalamocortical network.
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