Doyère V, Srebro B, Laroche S
Laboratoire de Neurobiologie de l'Apprentissage et de la Mémoire, Centre National de la Recherche Scientifique Unité de Recherche Associée 1491, Université Paris-Sud, Orsay, France.
J Neurophysiol. 1997 Feb;77(2):571-8. doi: 10.1152/jn.1997.77.2.571.
We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.
我们研究了清醒大鼠齿状回内侧和外侧内嗅传入纤维中异突触性长时程抑制（LTD）以及先前建立的长时程增强（LTP）的去增强作用的特征。将大鼠制备用于慢性记录齿状回对内侧和外侧穿通通路激活的诱发电位。在清醒大鼠中进行的这项研究证实，在对外侧穿通通路进行高频刺激诱导LTP的同时，可在未激活的内侧穿通通路突触处诱导异突触性LTD。这种形式的LTD持续时间长，并且通过对被抑制通路进行强直刺激可使其逆转。相比之下，对内侧穿通通路进行强直刺激对外侧通路仅产生较小的异突触效应，这表明齿状回的两条输入通路在诱导异突触性LTD的能力上并不对称。我们还研究了对一条通路进行高频刺激对另一条通路产生去增强作用的能力。我们发现，当内侧穿通通路首先诱导出LTP时，通过对外侧通路进行强直刺激可异突触性地诱导去增强作用。新建立的LTP（30分钟）以及通过数天重复强直刺激诱导并达到饱和的LTP均可被异突触性地去增强。此外，发现内侧穿通通路突触的去增强作用与外侧穿通通路突触中诱导的LTP大小呈线性相关，随后对去增强的内侧穿通通路进行强直刺激可将LTP恢复到一定程度，以抵消去增强作用。饱和及再增强实验为LTP的快速逆转反映内侧输入的真正去增强这一结论提供了明确支持。同样，与异突触性LTD一样，对内侧穿通通路进行强直刺激对先前在外侧通路中诱导的LTP影响很小。这些结果提供了证据，表明内侧穿通通路突触可被异突触性地抑制和去增强。它们表明，在完整大鼠中，来自外侧内嗅皮质的齿状回传入纤维中的突触变化对内侧内嗅传入纤维中正在进行的或近期的突触可塑性施加了强大的控制。
