Spike Timing-Dependent Plasticity in the Mouse Barrel Cortex Is Strongly Modulated by Sensory Learning and Depends on Activity of Matrix Metalloproteinase 9.

Experience and learning in adult primary somatosensory cortex are known to affect neuronal circuits by modifying both excitatory and inhibitory transmission. Synaptic plasticity phenomena provide a key substrate for cognitive processes, but precise description of the cellular and molecular correlates of learning is hampered by multiplicity of these mechanisms in various projections and in different types of neurons. Herein, we investigated the impact of associative learning on neuronal plasticity in distinct types of postsynaptic neurons by checking the impact of classical conditioning (pairing whisker stroking with tail shock) on the spike timing-dependent plasticity (t-LTP and t-LTD) in the layer IV to II/III vertical pathway of the mouse barrel cortex. Learning in this paradigm practically prevented t-LTP measured in pyramidal neurons but had no effect on t-LTD. Since classical conditioning is known to affect inhibition in the barrel cortex, we examined its effect on tonic GABAergic currents and found a strong downregulation of these currents in the layer II/III interneurons but not in pyramidal cells. Matrix metalloproteinases emerged as crucial players in synaptic plasticity and learning. We report that the blockade of MMP-9 (but not MMP-3) abolished t-LTP having no effect on t-LTD. Moreover, associative learning resulted in an upregulation of gelatinolytic activity within the "trained" barrel. We conclude that LTP induced by spike timing-dependent plasticity (STDP) paradigm is strongly correlated with associative learning and critically depends on the activity of MMP-9.