Blocking matri x metalloproteinase-9 activity in the central amygdala decreases c-Fos protein expression following apetitively motivated training

In addition to being widely investigated as a marker of neuronal activity, expression of c-Fos has also been shown to be closely linked with synaptic plasticity, learning and memory. Understanding c-Fos-dependent molecular underpinnings of the synaptic plasticity may be achieved by following its transcription-regulatory function, i.e. by identifying the genes it controls. MMP-9 (matrix metalloproteinase-9), an extracellular endopeptidase which cleaves extracellular matrix proteins and plays an important role in synaptic plasticity, learning and memory, have been documented to be c-Fos/AP-1 regulated at the transcriptional level, also in the activated neurons. We hypothesized that following the extracellular release of MMP-9 supply, c-Fos upregulation is necessary for MMP-9 replenishment. To test this hypothesis we injected PLGA nanoparticles releasing TIMP-1 (tissue inhibitor of matrix metalloproteinases-1, a specific inhibitor of MMP-9) to the central amygdala of mice. Then, the animals learned the appetitively motivated behavioral task in the IntelliCage system, which had been previously shown to specifically increase c-Fos expression in the central amygdala. We showed that blocking MMP-9 results in significantly decreased expression of c-Fos protein. This result is consistent with the hypothesis of the role of c-Fos in MMP-9 replenishment.