Metaplastic regulation of neocortical long-term depression in vivo is sensitive to distinct phases of conditioned taste aversion

Abstract

Metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Accumulated evidence has proposed that metaplasticity contributes to network function and cognitive processes such as learning and memory. In this regard, it has been observed that training in several behavioral tasks modifies the possibility to induce subsequent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). For instance, our previous studies have shown that conditioned taste aversion (CTA) training prevents the induction of in vivo LTP in the projection from the basolateral nucleus of the amygdala to the insular cortex (BLA-IC). Likewise, we reported that extinction of CTA allows induction but not maintenance of LTP in the same pathway. Besides, we showed that it is possible to express in vivo low-frequency stimulation LTD in the BLA-IC projection and that its induction prior to CTA training facilitates the extinction of this task. However, until now, little is known about the participation of LTD on metaplastic processes. The present study aimed to analyze whether CTA training modifies the expression of in vivo LTD in the BLA-IC projection. To do so, animals received low-frequency stimulation to induce IC-LTD 48 h after CTA training. Our results show that CTA training occludes the subsequent induction of LTD in the BLA-IC pathway in a retrieval-dependent manner. These findings reveal that CTA elicits a metaplastic regulation of long-lasting changes in the IC synaptic strength, as well as that specific phases of learning differentially take part in adjusting the expression of synaptic plasticity in neocortical regions.