Involvement of the T-type Calcium channel in discharge pattern and interaction of ventral posterior and reticular thalamic neurons

Autor: Yi-Fang Liao, 廖儀芳
Rok vydání: 2011
Druh dokumentu: 學位論文 ; thesis
Popis: 99
Low-threshold T-type calcium channels (T-channels) are critically important in the generation of thalamic burst activities. Different subtypes of T-channel distributed differentially in thalamic ventroposterior nucleus (VP, Cav3.1) and reticular thalamic nucleus (RT, Cav3.2 and Cav3.3). Furthermore, T-channel knockout (KO) mice showed contrast nociceptive behaviors, such that an increase was seen in Cav3.1 KO and a decrease in Cav3.2 KO. Considering the important role in sensory relay function of VP neuron and it’s densely reciprocal connection to GABAergic RT, it is important to examine VP and RT neurons simultaneous and compare their bursting activity in the T-channel KO mice. We used multi-channel single-unit recording method to study the changes in the firing property of VP and RT neurons in Cav3.1 and 3.2 KO mice in the anesthetized condition. In the first part of this study, we compared the spontaneous burst and tonic firing activities of VP and RT neurons among the two KO and their wild-type (WT) control mice. We found that in WT mice, 50% somatosensory RT neurons and less than 1% VP neurons were nociceptive. Percentages of nociceptive neurons decreased in the RT and VP in the Cav3.2 KO mice. Cav3.1 KO lost most burst firing in VP. In Cav3.2 KO, we found fewer and weakened RT burst firing and tonic RT firing lost their regularity. Interestingly, Cav3.2 KO also showed increased and stronger VP burst firing. In the second part of the present study, the responsiveness of the VP and RT burst firing to tactile and noxious stimuli in the Cav3.1 and Cav3.2 KO were studied. We found that the innocuous stimulation induced response firing in VP and RT neurons were mostly burst firing, whereas noxious stimulation induced mostly single spikes. T-channel KO mice showed similar response pattern. Cav3.1 KO particularly showed less proportion of VP burst firing in response to light touch stimulation and RT neurons showed more prominently single spike firings in response to pinch stimulation compare to their WT control mice. In Cav3.2 KO, VP and RT neurons showed reduced bursts of mechanical innocuous stimulation evoked response. In laser heat stimulation evoked responses, Cav3.2 KO RT neurons showed reduced burst firing response in both percentage and amplitude. Furthermore, Cav3.2 KO VP and RT neurons had longer response onset latencies in 1.5 T electrical stimulation and laser heat stimulation. In the third part of this study, we analyzed thalamic neuron activities in a longer time scale to see whether T channel deficits interfered with intra thalamic interactions. A slow reciprocal VP and RT oscillations was found. This oscillation was modality independent, but it was weakened in Cav3.1 and Cav3.2 KO mice. The results showed that T-channel is important in thalamic burst rhythm, slow rhythm, and thalamocortical neuron and reticular neuron interaction. These factors may contribute to rodent pain function. In conclusion, T-channels are involved in thalamic VP and RT rhythmic activities. The changes in thalamic rhythmicity might contribute to the changed nocifensive behaviors in the T channel defective mice.
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