Sagheddu Claudia, Stojanovic Tamara, Kouhnavardi Shima, Savchenko Artem, Hussein Ahmed M, Pistis Marco, Monje Francisco J, Plasenzotti Roberto, Aufy Mohammed, Studenik Christian R, Lubec Jana, Lubec Gert
Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
Programme for Proteomics, Paracelsus Medical University, Salzburg, Austria.
Front Aging Neurosci. 2024 Feb 26;16:1357347. doi: 10.3389/fnagi.2024.1357347. eCollection 2024.
Deterioration of cognitive functions is commonly associated with aging, although there is wide variation in the onset and manifestation. Albeit heterogeneity in age-related cognitive decline has been studied at the cellular and molecular level, there is poor evidence for electrophysiological correlates. The aim of the current study was to address the electrophysiological basis of heterogeneity of cognitive functions in cognitively Inferior and Superior old (19-20 months) rats in the ventral tegmental area (VTA) and the hippocampus, having Young (12 weeks) rats as a control. The midbrain VTA operates as a hub amidst affective and cognitive facets, processing sensory inputs related to motivated behaviours and hippocampal memory. Increasing evidence shows direct dopaminergic and non-dopaminergic input from the VTA to the hippocampus.
Aged Superior and Inferior male rats were selected from a cohort of 88 animals based on their performance in a spatial learning and memory task. Using single-cell recording in the VTA, we examined the electrical activity of different neuronal populations (putative dopaminergic, glutamatergic and GABAergic neurons). In the same animals, basal synaptic transmission and synaptic plasticity were examined in hippocampal slices.
Electrophysiological recordings from the VTA and hippocampus showed alterations associated with aging , together with differences specifically linked to the cognitive status of aged animals. In particular, the bursting activity of dopamine neurons was lower, while the firing frequency of glutamatergic neurons was higher in VTA of Inferior old rats. The response to high-frequency stimulation in hippocampal slices also discriminated between Superior and Inferior aged animals.
This study provides new insight into electrophysiological information underlying compromised cerebral ageing. Further understanding of brain senescence, possibly related to neurocognitive decline, will help develop new strategies towards the preservation of a high quality of life.
认知功能的衰退通常与衰老相关，尽管其发作和表现存在很大差异。尽管在细胞和分子水平上已经研究了与年龄相关的认知衰退的异质性，但关于电生理相关性的证据却很少。本研究的目的是探讨腹侧被盖区（VTA）和海马体中认知能力较差和较好的老年（19 - 20个月）大鼠认知功能异质性的电生理基础，并以年轻（12周）大鼠作为对照。中脑VTA在情感和认知方面起着枢纽作用，处理与动机行为和海马体记忆相关的感觉输入。越来越多的证据表明，VTA向海马体有直接的多巴胺能和非多巴胺能输入。
根据88只雄性大鼠在空间学习和记忆任务中的表现，从其中挑选出老年认知能力较好和较差的大鼠。我们在VTA中使用单细胞记录技术，检测了不同神经元群体（假定的多巴胺能、谷氨酸能和γ-氨基丁酸能神经元）的电活动。在同一只动物中，还检测了海马体切片中的基础突触传递和突触可塑性。
来自VTA和海马体的电生理记录显示了与衰老相关的变化，以及与老年动物认知状态特别相关的差异。特别是，老年认知能力较差的大鼠VTA中多巴胺能神经元的爆发活动较低，而谷氨酸能神经元的放电频率较高。海马体切片对高频刺激的反应也区分了老年认知能力较好和较差的动物。
本研究为受损脑衰老的电生理信息提供了新的见解。对可能与神经认知衰退相关的脑衰老的进一步理解，将有助于制定新的策略来维持高质量的生活。
