Samuel Nir, Kahana Eilat, Taub Aryeh, Reitich-Stolero Tamar, Paz Rony, Raz Aeyal
Anesthesiology. 2021 May 1;134(5):734-747. doi: 10.1097/ALN.0000000000003732.
Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation.
Two nonhuman primates underwent aversive tone-odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery.
Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amygdala and dorsal anterior cingulate cortex were positively correlated between acquisition and retention (amygdala, n = 101, r = 0.51, P < 0.001; dorsal anterior cingulate cortex, n = 121, r = 0.32, P < 0.001). Neural responses during acquisition under anesthetics were stronger in sessions exhibiting memory formation than those that did not (amygdala median response ratio, 0.52 versus 0.33, n = 101, P = 0.021; dorsal anterior cingulate cortex median response ratio, 0.48 versus 0.32, n = 121, P = 0.012). The change in firing rate of amygdala neurons during acquisition was correlated with the size of stimuli-conditioned inspiratory response during retention (n = 101, r = 0.22 P = 0.026). Thus, amygdala and dorsal anterior cingulate cortex responses during acquisition under anesthetics predicted retention. Respiratory unconditioned responses to the aversive odor anesthetics did not differ from saline controls.
These results suggest that the amygdala-dorsal anterior cingulate cortex circuit maintains its role in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation.
麻醉剂旨在防止对不愉快经历的记忆。杏仁核和背侧前扣带回皮质参与形成情感和效价驱动的记忆。据推测，该神经回路在镇静状态下仍发挥作用。
两只非人灵长类动物在氯胺酮或咪达唑仑（分别为1至8毫克/千克和0.1至0.8毫克/千克）诱导的镇静状态下接受厌恶性音调-气味条件反射。主要结果是表明记忆形成的行为和神经学证据。本研究同时测量了条件性吸气变化以及杏仁核和背侧前扣带回皮质中单个神经元在习得过程中对预期厌恶性嗅觉刺激出现时的放电率变化，并在恢复后测试了它们的记忆保持情况。
在麻醉状态下的59次实验中有26次形成了厌恶性记忆（低剂量和高剂量咪达唑仑分别为29次中的16次、30次中的10次，氯胺酮分别为30次中的5次、29次中的21次）。杏仁核和背侧前扣带回皮质中的单个神经元反应在习得和记忆保持之间呈正相关（杏仁核，n = 101，r = 0.51，P < 0.001；背侧前扣带回皮质，n = 121，r = 0.32，P < 0.001）。在表现出记忆形成的实验中，麻醉状态下习得过程中的神经反应比未表现出记忆形成的实验更强（杏仁核中位反应率，0.52对0.33，n = 101，P = 0.021；背侧前扣带回皮质中位反应率，0.48对0.32，n = 121，P = 0.012）。习得过程中杏仁核神经元的放电率变化与记忆保持过程中刺激条件性吸气反应的大小相关（n = 101，r = 0.22，P = 0.026）。因此，麻醉状态下习得过程中杏仁核和背侧前扣带回皮质的反应可预测记忆保持情况。对厌恶性气味麻醉剂的呼吸非条件反应与生理盐水对照组无差异。
这些结果表明，在氯胺酮和咪达唑仑镇静下的非人灵长类动物中，杏仁核-背侧前扣带回皮质神经回路在厌恶性记忆的习得和维持中仍发挥作用，且刺激效价足以驱动记忆形成。
