Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Department of Psychology, University of Cambridge, Cambridge, UK.
J Psychopharmacol. 2020 Dec;34(12):1371-1381. doi: 10.1177/0269881120965880. Epub 2020 Oct 24.
Thalamic subregions mediate various cognitive functions, including attention, inhibitory response control and decision making. Such neuronal activity is modulated by cholinergic thalamic afferents and deterioration of such modulatory signaling has been theorised to contribute to cognitive decline in neurodegenerative disorders. However, the thalamic subnuclei and cholinergic receptors involved in cognitive functioning remain largely unknown.
We investigated whether muscarinic or nicotinic receptors in the mediodorsal thalamus and anterior thalamus contribute to rats' performance in the five-choice serial reaction time task, which measures sustained visual attention and impulsive action.
Male Long-Evans rats were trained in the five-choice serial reaction time task then surgically implanted with guide cannulae targeting either the mediodorsal thalamus or anterior thalamus. Reversible inactivation of either the mediodorsal thalamus or anterior thalamus were achieved with infusions of the γ-aminobutyric acid-ergic agonists muscimol and baclofen prior to behavioural assessment. To investigate cholinergic mechanisms, we also assessed the behavioural effects of locally administered nicotinic (mecamylamine) and muscarinic (scopolamine) receptor antagonists.
Reversible inactivation of the mediodorsal thalamus severely impaired discriminative accuracy and response speed and increased omissions. Inactivation of the anterior thalamus produced less profound effects, with impaired accuracy at the highest dose. In contrast, blocking cholinergic transmission in these regions did not significantly affect five-choice serial reaction time task performance.
CONCLUSIONS/INTERPRETATIONS: These findings show the mediodorsal thalamus plays a key role in visuospatial attentional performance that is independent of local cholinergic neurotransmission.
丘脑亚区介导各种认知功能，包括注意力、抑制反应控制和决策。这种神经元活动受到胆碱能丘脑传入的调节，并且这种调节信号的恶化被认为导致神经退行性疾病中的认知下降。然而，涉及认知功能的丘脑亚核和胆碱能受体在很大程度上仍然未知。
我们研究了中背侧丘脑和前丘脑的毒蕈碱或烟碱受体是否有助于大鼠在五选择连续反应时间任务中的表现，该任务测量持续的视觉注意力和冲动行为。
雄性 Long-Evans 大鼠在五选择连续反应时间任务中接受训练，然后接受手术植入针对中背侧丘脑或前丘脑的导向套管。在行为评估之前，通过注射γ-氨基丁酸能激动剂 muscimol 和 baclofen 来实现中背侧丘脑或前丘脑的可逆失活。为了研究胆碱能机制，我们还评估了局部给予烟碱（美加明）和毒蕈碱（东莨菪碱）受体拮抗剂的行为效应。
中背侧丘脑的可逆失活严重损害了辨别准确性和反应速度，并增加了遗漏。前丘脑的失活产生的影响较小，在最高剂量时准确性受损。相比之下，阻断这些区域的胆碱能传递并没有显著影响五选择连续反应时间任务的表现。
结论/解释：这些发现表明，中背侧丘脑在视觉空间注意力表现中起着关键作用，而不依赖于局部胆碱能神经传递。
