Figure 3.

Sliding threshold metaplasticity in the visual system and in cortico-striatal excitatory rewarded and unrewarded synapses. A, Synapses between lateral intracortical neurons and V1 layer 2/3 (L2/3) pyramidal neurons. When a DE is reversed by an LE, sliding homeostatic plasticity occurs. Newly synthetized Homer1a constitutively activates mGluR5, which inhibits NMDARs through a direct interaction (Chokshi et al., 2019b). This leads to an increase in the threshold required for LTP induction. B, Cortico-striatal synapses. Two types of sliding homeostatic plasticity occur. In the absence of D1 dopamine receptor stimulation, activation of these synapses (unrewarded synapses) triggers, in downstream striatal neurons, similar signaling events as we have seen above in the visual system after LE. A decrease in the LTP/LTD ratio is observed. In contrast, when D1 receptors are activated before activation of the cortico-striatal synapses (rewarded synapses), Homer1a is synthetized constitutively and activates mGluR5. In addition, the D1 receptor-cAMP-ERK activated pathway allows the phosphorylation and isomerization (by PIN) of mGluR5. The phosphorylated and isomerized mGluRs activate (instead of inhibiting) NMDARs by an unknown mechanism, leading to an increase in the LTP/LTD ratio (Marton et al., 2015). *The mGluR1,5 receptors are constitutively activated.