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Over the past century of memory research, the interplay between initial and later-learned information in determining long-term memory retention has been of central interest. A likely factor for determining whether initial and later memories interfere with or strengthen each other is semantic relatedness. Relatedness has been shown to boost initial memory and increase the interdependence between earlier and more recent experiences in memory.

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Ideally, removing outdated information from working memory (WM) should have two consequences: The removed content should be less accessible (removal costs), and other WM content should benefit from the freeing up of WM capacity (removal benefits). Robust removal benefits and removal costs have been demonstrated when people are told to forget items shortly after they were encoded (immediate removal). However, other studies suggest that people might be unable to selectively remove items from an already encoded set of items (delayed removal).

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Recent work demonstrated that activation of spinal D1 and D5 dopamine receptors (D1/D5Rs) facilitates non-Hebbian long-term potentiation (LTP) at primary afferent synapses onto spinal projection neurons. However, the cellular localization of the D1/D5Rs driving non-Hebbian LTP in spinal nociceptive circuits remains unknown, and it is also unclear whether D1/D5R signaling must occur concurrently with sensory input in order to promote non-Hebbian LTP at these synapses. Here we investigate these issues using cell-type-selective knockdown of D1Rs or D5Rs from lamina I spinoparabrachial neurons, dorsal root ganglion (DRG) neurons, or astrocytes in adult mice of either sex using Cre recombinase-based genetic strategies.

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