大鼠次級與初級體感覺皮層聯絡網路及功能之比較

Abstract

本研究利用神經解剖追蹤技術以及電生理記錄探討大鼠在體感覺系統中的聯絡網路以及功能。在第一個部分的實驗，我們利用追蹤腹尾外側核(ventroposterior thalamic nucleus, VPL)、初級體感覺皮層(primary somatosensory cortex, S1)以及次級體感覺皮層(secondary somatosensory cortex, S2)之間的連結探討次級體感覺皮層在體感覺系統中的位階。我們的主要發現包括了: 1) VPL中的前後兩群神經元各自投射至同側的S1和S2，其中有一小部分的提供分支至兩個腦區; 2) S1和S2之間有對稱的連結; 3) S1和S2 神經元皆投射至相對應的VPL區域。以上這些結果說明了S2和S1在體感覺訊息路徑中佔有相等的地位。 除了VPL之外，後視丘核(posterior nuclear complex, POm)和S1以及S2之間的連結關係目前尚未釐清。早期的研究指出S1鬍鬚區域的第五層神經細胞提供大型的神經末稍 (直徑約為3-10 μm)至POm。此類的神經末稍已被證實可以影響突觸後細胞的神經特性。為了瞭解是否其他的身體區域以及其他的腦區對於POm也具有類似的影響力，我們觀察S1和S2前腳以及後腳區域投射至視丘的末稍型態以及分佈位置。結果顯示：1) 除了鬍鬚區域以外，前腳以及後腳的大腦區也提供大型的神經末稍(3-5 μm)至POm; 2) S2也具有提供此類大型的神經末稍至POm; 3) 除了POm以外，來自S1和S2的大型神經末稍也分佈在VPL的腹外側。此些發現證實了S2和S1同時都具有提供大型神經末稍至特定視丘核區，例如POm的功能。此外，此項發現說明了在感覺系統中，可以藉由匯集不同腦區的投射同時調控訊息的傳遞。 我們另外以Thy1-GFPm小鼠為實驗動物研究大腦皮層對於視丘的投射現象。在這部分的實驗結果包括了: 1) 內生性的GFP標定大型神經末稍分佈於VP的背內側延伸至腹外側; 2) S1前腳區域的神經元投射大型的神經末稍至POm以及3)VPL的腹外側），而且和內生性的GFP標定大型神經末稍分佈於一樣的區域。根據以上實驗結果，我們推測齧齒目動物的VPL可能具有分化為中心核區(core)和外層核區(shell)的現象。 在最後一個部分的實驗，我們藉由比較S1和S2神經元對於觸覺刺激(風吹)以及痛覺刺激(雷射熱)的反應探討S2如何處理周邊體感覺刺激。S1和S2神經群對於周邊刺激有相當類似的反應特性，包括了類似的起始時間、到達最大反應的時間以及放電頻率。另外，根據觀察放電頻率的變化，我們發現S1和S2神經元對於不同強度的觸覺和痛覺刺激具有相當類似的分辨能力。這兩群細胞最主要的不同在於S2神經元具有比較大的體感覺接收區。我們推測此差異可能是來自於S1和S2接收不同群視丘投射所造成的。 綜合以上的結果，我們推論S2和S1在體感覺系統的聯絡網路中佔有對等的位階，而且對於處理周邊的觸覺以及痛覺刺激中扮演有相當類似的角色。

The anatomical hierarchy and functional role of secondary somatosensory cortex (S2) in rats were investigated by neuroanatomical methods and electrophysiological recording in present study. The hierarchical relationship of the primary somatosensory cortex (S1) and S2 is investigated by examining the connections between ventroposterior thalamic nucleus (VPL), S1 and S2. Our main findings are: 1) VPL neurons provide direct inputs to ipsilateral S1 and S2 in an antero-posterior manner, with a minority of percentage in the intermediate zone send bifurcate axons to S1 and S2 simultaneously; 2) S1 and S2 are connected reciprocally and symmetrically in a somatotopic order; 3) Both S1 and S2 neurons provide small terminals to corresponding VPL fields. The results validated the equivalent hierarchy of S2 and S1 in somatosensory ascending pathway. The relationship of S1 and S2 to thalamus was further examined with terminal pattern of the corticothalamic fibers. POm have been shown previously to receive large sized boutons (3-10 μm in diameter) arising from layer V of the S1 barrel field. To determine whether other body parts and/ or other somatosensory cortical areas, such as S2, may also contribute to such unique large terminals within POm, the distribution and morphology of descending axons extending from S1 and S2 forepaw and hindpaw representations were examined. We found that: 1) Other body parts such as forepaw and hindpaw of the S1 also provide large boutons (3-5 μm) to the POm; 2) Not only S1 but also S2 contribute such sources. 3) These giant corticothalamic terminals from S1 and S2 were found not only in POm, but also around the shell/ edge area of the ventroposterior nucleus. Our findings suggested that in resemblance to S1, S2 neurons also participate in the cortico-thalamo-cortical circuits via providing large terminations to particular dorsal thalamic nuclei, for example, POm. Hence, the large terminals may simultaneously modulate on-going thalamocortical somatosensory information via multiple channels. In addition, the intrinsic GFP expressed large terminals and corticothalamic terminations arising from S1 forepaw fields were examined in Thy1-GFPm mice. Our preliminary results showed that: 1) intrinsic GFP-positive large terminals were distributed in the dorsomedial and ventrolateral fringe of VP; 2) S1 forepaw neurons provide large boutons to the POm; 3) these large corticothalamic terminals from S1 were also found in the ventrolateral shell/ edge area of VP, co-localized within the fringe region delineated by GFP-positive large terminals. The findings suggest that VP is anatomically partitioned into a “core” and a “shell” sub-region in rodents. Finally, we examined the functional role of S2 by comparing their air puffs (innocuous stimulation)- and laser heat irradiation (noxious stimulation)- evoked neuronal activities with S1 neurons in conscious behaving rats. Several similarities between the two populations were found in the present study, including: 1) Both S2 and S1 forepaw neurons showed dominant responses to contralateral forepaw stimulation with similar latency and amplitude in either innocuous or noxious stimulation. 2) S2 and S1 neurons showed equivalent intensity coding ability for innocuous and noxious inputs. Nevertheless, the receptive fields of S2 neurons are larger than S1 neurons. Based on the anatomical data in the present study, we suggested the diversity may be resulted from segregated thalamic inputs. In conclusion, we suggested that S2 and S1 neurons occupy parallel anatomical positions in somatosensory system, and play comparable roles in processing peripheral innocuous and noxious information.