Silent glutamatergic synapses and long-term facilitation in spinal dorsal horn neurons

Abstract

Neurons in the superficial dorsal horn of the spinal cord are important for conveying sensory information from the periphery to the central nervous system. It has been proposed that some synapses between primary afferent fibers and spinal dorsal horn neurons are inefficient or silent. Ineffective sensory transmission could result from a small postsynaptic current that fails to depolarize the cell to threshold for an action potential or a cell with a normal postsynaptic current but an increased threshold for action potentials. One possible mechanism for ineffective synapses is the existent of silent glutamatergic synapses. In silent synapses, postsynaptic dorsal horn neurons lack functional AMPA/KA receptors and no synaptic responses are detected even when glutamate is released from presynaptic sensory afferent fibers. Serotonin (5-HT), a major neurotransmitter of the raphe-spinal projecting pathway, transforms silent glutamatergic synapses into functional ones by recruiting postsynaptic functional AMPA receptors. AMPA receptor interaction with PDZ-containing proteins is critical for 5-HT induced recruitment. Silent synapses, as well as their recruitment mechanisms, are developmentally regulated and can still be found in adult synapses. However, they are “functional” and contribute to some sensory transmission. The recruitment of AMPA receptors into pure NMDA receptor containing sensory synapses requires coactivation of 5-HT and postsynaptic adenylyl cyclases. The recruitment of silent glutamatergic synapses provides a synaptic mechanism for spinal senstization in pathological pain, including possible pheonotype switching of dorsal horn neurons. These results suggest that the transformation of silent glutamatergic synapses may serve as a cellular mechanism for central plasticity in the spinal cord.