Sensory experience can shape the synaptic connectivity of the sensory cortices during its maturation in infants, and during learning in adults. Besides sensory inputs, cortical plasticity also depends on neuromodulatory inputs conveying information on the individual's behavioral state. As a result, experience-dependent cortical plasticity requires the individual to be awake and attentive. In contrast, passive experience usually does not leave a permanent trace on cortical connectivity. The traditional view on the neuromodulatory control of cortical plasticity has emphasized their role in increasing neural excitability, improving the signal to noise ratio, and their role in controlling the propagation of activity through the cortex. This Chapter will review the notion that neuromodulators control sensory-induced plasticity at a synaptic level by setting the gain of mechanisms like long-term potentiation (LTP) and long-term depression (LTD). We will discuss how intracellular signal generated by different neuromodulator receptors can interact with the biochemical machinery responsible for LTP and LTD. Finally, we will discuss the emerging notion that different neuromodulator receptors can specifically control LTP and LTD by regulating the trafficking of glutamate AMPA receptors in and out of the synapse.
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