Electrophysiological study of long-term potentiation in cortical and subcortical synapses of alert behaving mice

Resumen

Long-term potentiation (LTP) is an experimental procedure commonly used to study synaptic plasticity, since it shares certain mechanisms with neuronal learning and memory processes. LTP consists of an increase of the synaptic response to a control stimulus following the presentation of a high-frequency stimulation (HFS) train to an afferent pathway. This technique was first reported in the hippocampus and it still widely studied mostly due to its high excitability and its laminar nature, which facilitates the location of defined synapses. Nonetheless, there has recently been an increasing interest about how LTP affects other cortical and subcortical structures, like in the synapses between the prefrontal cortex (mPFC) and the basolateral amygdala (BLA). These three brain areas are highly involved in memory encoding and consolidation. The main goal of this study was to get a better understanding of how LTP affects the synaptic plasticity of certain hippocampal and amygdalo-cortical synapses. Although the vast majority of previous research on this topic has been performed in vitro, we did carry out in vivo recordings using electrodes chronically implanted in alert behaving mice, with the idea of obtaining the best possible physiological information. We recorded field excitatory post-synaptic potentials (fEPSPs) to characterize input/output (I/O) curves, paired-pulse stimulation, and LTP of the selected synapses. In the hippocampus, the pertinent tests revealed similar basic electrophysiological properties, a fact that enables an easier comparison of LTP characteristics. The stimulation of the perforant pathway (PP), considered the main input of the hippocampus, with HFS trains evoked LTP in the selected hippocampal synapses, affecting in different manners their short-term plasticity. Importantly, we observed the presence of significant LTP in the contralateral CA1 (cCA1) area following the control stimulation of non-HFS- activated pathways. These results indicate that LTP appears as a physiological process present in synapses even located far away from the HFS-stimulated afferent pathway. We also performed depth-profile recordings to determine differences in fEPSP latencies. On the other hand, data collected from the BLA and mPFC reported differences in the interstimulus time needed for their higher facilitation¿20 ms in the mPFC-BLA synapse and 40 ms for the BLA-mPFC synapse. Finally, HFS could only evoke LTP in the mPFC-BLA synapse, while mPFC remained without significant potentiation after the HFS of the BLA.