RT Journal Article SR Electronic T1 Multiple Local Synaptic Modifications at Specific Sensorimotor Connections after Learning Are Associated with Behavioral Adaptations That Are Components of a Global Response Change JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4363 OP 4371 DO 10.1523/JNEUROSCI.2647-19.2020 VO 40 IS 22 A1 Tam, Shlomit A1 Hurwitz, Itay A1 Chiel, Hillel J. A1 Susswein, Abraham J. YR 2020 UL http://www.jneurosci.org/content/40/22/4363.abstract AB Learning causes local changes in synaptic connectivity and coordinated, global changes affecting many aspects of behavior. How do local synaptic changes produce global behavioral changes? In the hermaphroditic mollusc Aplysia, after learning that food is inedible, memory is expressed as bias to reject a food and to reduce responses to that food. We now show that memory is also expressed as an increased bias to reject even a nonfood object. The increased bias to rejection is partially explained by changes in synaptic connections from primary mechanoafferents to five follower neurons with well defined roles in producing different feeding behaviors. Previously, these mechanoafferents had been shown to play a role in memory consolidation. Connectivity changes differed for each follower neuron: the probability that cells were connected changed; excitation changed to inhibition and vice versa; and connection amplitude changed. Thus, multiple neural changes at different sites underlie specific aspects of a coordinated behavioral change. Changes in the connectivity between mechanoafferents and their followers cannot account for all of the behavioral changes expressed after learning, indicating that additional synaptic sites are also changed. Access to the circuit controlling feeding can help determine the logic and cellular mechanisms by which multiple local synaptic changes produce an integrated, global change in behavior.SIGNIFICANCE STATEMENT How do local changes in synapses affect global behavior? Studies on invertebrate preparations usually examine synaptic changes at specific neural sites, producing a specific behavioral change. However, memory may be expressed by multiple behavioral changes. We report that a change in behavior after learning in Aplysia is accomplished, in part, by regulating connections between mechanoafferents and their synaptic followers. For some followers, the connection probabilities change; for others, the connection signs are reversed; in others, the connection strength is modified. Thus, learning produces changes in connectivity at multiple sites, via multiple synaptic mechanisms that are consistent with the observed behavioral change.