Instituto de Investigação e Inovação em Saúde (i3S), Pain Neurobiology Group, Universidade do Porto, Porto, Portugal.
Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.
Eur J Pain. 2022 Aug;26(7):1546-1568. doi: 10.1002/ejp.1982. Epub 2022 May 31.
Prelimbic medial prefrontal cortex (PL-mPFC) and nucleus accumbens core region (NAcc) play an important role in supporting several executive cognitive mechanisms, such as spatial working memory (WM). Recently, this circuit has been also associated with both sensory and affective components of pain. However, it is still unclear whether this circuit is endogenously engaged in neuropathic pain-related cognitive dysfunctions.
To answer this question, we induced the expression of halorhodopsin in local PL-mPFC neurons projecting to NAcc, and then selectively inhibited the terminals of these neurons in the NAcc while recording neural activity during the performance of a delayed non-match to sample (DNMS) spatial WM task. Within-subject behavioural performance and PL-mPFC to NAcc circuit neural activity was assessed after the onset of a persistent rodent neuropathic pain model-spared nerve injury (SNI).
Our results revealed that the induction of the neuropathy reduced WM performance, and altered the interplay between PL-mPFC and NAcc neurons namely in increasing the functional connectivity from NAcc to PL-mPFC, particularly in the theta-band spontaneous oscillations; in addition, these behavioural and functional perturbations were partially reversed by selective optogenetic inhibition of PL-mPFC neuron terminals into the NAcc during the DNMS task delay-period, without significant antinociceptive effects.
Altogether, these results strongly suggest that the PL-mPFC excitatory output into the NAcc plays an important role in the deregulation of WM under pain conditions.
Selective optogenetic inhibition of prefrontal-striatal microcircuit reverses pain-related working memory deficits but has no significant impact on pain responses. Neuropathic pain underlies an increase of functional connectivity between the nucleus accumbens core area and the prelimbic medial prefrontal cortex mediated by theta-band activity.
额眶部皮质前内侧（PL-mPFC）和伏隔核核心区（NAcc）在支持多种执行认知机制方面发挥着重要作用，例如空间工作记忆（WM）。 最近，该回路还与疼痛的感觉和情感成分有关。 但是，尚不清楚该回路是否内在参与了与神经性疼痛相关的认知功能障碍。
为了回答这个问题，我们在投射到 NAcc 的局部 PL-mPFC 神经元中诱导表达了 halorhodopsin，然后在记录执行延迟非匹配样本（DNMS）空间 WM 任务期间的神经活动时，选择性地抑制了这些神经元在 NAcc 中的末梢。 在持续的啮齿动物神经性疼痛模型（ spared nerve injury，SNI）发作后，评估了行为表现和 PL-mPFC 到 NAcc 回路的神经活动。
我们的结果表明，神经病的诱导降低了 WM 性能，并改变了 PL-mPFC 和 NAcc 神经元之间的相互作用，即增加了从 NAcc 到 PL-mPFC 的功能连接，特别是在θ频带自发振荡中；此外，这些行为和功能扰动在 DNMS 任务延迟期间通过选择性光遗传学抑制 PL-mPFC 神经元末梢进入 NAcc 而部分逆转，而没有明显的镇痛作用。
总而言之，这些结果强烈表明，PL-mPFC 兴奋输出到 NAcc 在疼痛条件下 WM 失调中起着重要作用。
选择性光遗传学抑制前额叶-纹状体微电路可逆转与疼痛相关的工作记忆缺陷，但对疼痛反应没有明显影响。 神经性疼痛导致θ频带活动介导的伏隔核核心区与额眶部皮质前内侧之间的功能连接增加。
