Neuron
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The collapse of neural networks important for memory and cognition, including death of neurons and degeneration of synapses, causes the debilitating dementia associated with Alzheimer's disease (AD). We suggest that synaptic changes are central to the disease process. ⋯ Further, the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of transsynaptic spread of pathological forms of tau. These two key phenomena, synapse loss and the spread of pathology through the brain via synapses, make it critical to understand the physiological and pathological roles of amyloid beta and tau at the synapse.
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The original formulation of Gate Control Theory (GCT) proposed that the perception of pain produced by spinal cord signaling to the brain depends on a balance of activity generated in large (nonnociceptive)- and small (nociceptive)-diameter primary afferent fibers. The theory proposed that activation of the large-diameter afferent "closes" the gate by engaging a superficial dorsal horn interneuron that inhibits the firing of projection neurons. ⋯ The present Review highlights the complexity of superficial dorsal horn circuitry and addresses the question whether the premises outlined in GCT still have relevance today. By examining the dorsal horn circuits that underlie the transmission of "pain" and "itch" messages, we also address the extent to which labeled lines can be incorporated into a contemporary view of GCT.