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

Abstract

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. Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-0174-y) contains supplementary material, which is available to authorized users.

Changes in Gene and Protein Expression of Metalloproteinase-2 and -9 and Their Inhibitors TIMP2 and TIMP3 in Different Parts of Fluoride-Exposed Rat Brain

“…This is confirmed by the findings from a study on rats in which learning impairment was observed as a result of the administration of MMP9 inhibitors [62]. In a study investigating the plasticity of the somatosensory cortex, it was demonstrated that LTP induced by the spike timing-dependent plasticity (STDP) paradigm is strongly correlated with associative learning and critically depends on the activity of MMP9 [63]. It was also reported that the expression of MMP2 and MMP9 (mRNA and protein concentration) differs in people with recurrent depressive disorders and impaired cognitive functions compared to healthy controls [64].…”

Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9

“…The weakening of thalamic inputs to FS INs is a novel role for MMP-9, which is typically associated with the growth and strengthening of excitatory synapses onto excitatory neurons ( Kaliszewska et al, 2012 ; Lebida and Mozrzymas, 2016 ; Michaluk et al, 2011 ; Ganguly et al, 2013 ), but see ( Romberg et al, 2013 ). Indeed, inhibition of MMP-9 blocks the maintenance of long-term potentiation (LTP) ( Wiera et al, 2013 ; Nagy et al, 2006 ), and the enlargement of pyramidal neuron dendritic spines following tetanic stimulation of hippocampal CA1-CA3 synapses ( Wang et al, 2008 ; Szepesi et al, 2014 ).…”

Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons

“…The effect of conditioning, as seen with 2DG, is primarily in L4; the changes in neuronal interactions that were observed in L2/3 (Lebida and Mozrzymas, 2017;Rosselet et al, 2011;Urban-Ciecko et al, 2005) are not reflected in the expansion of the trained whisker representation in this layer. Moreover, in the somatosensory cortex, Denardo et al (2015) found strong input from L3 mainly to L6; therefore, the direct and powerful effect of L2/3 SOM-IN activity alteration on L4 is rather unlikely.…”