海马CA1区与眶额叶皮质的神经节律同步活动参与大鼠空间目标导向任务中的学习与记忆巩固

doi:10.12122/j.issn.1673-4254.2025.03.05

摘要/Abstract

摘要：

目的探究海马CA1区和眶额叶皮质（OFC）神经节律在空间目标导向任务中的作用机制。方法训练Long-Evans大鼠（n=4）在陆地式水迷宫（Cheese-board 迷宫）执行空间目标导向任务。空间目标导向任务分别设置学习前测试时期、学习前睡眠时期、学习时期、学习后睡眠时期和学习后测试时期。学习新奖赏位置前、后的测试时期用来评估大鼠对新、旧奖赏位置的记忆能力，学习两个新奖赏位置的时期用来评估大鼠对新奖赏位置的学习能力。在学习期内，将任务态划分为两种过程：目标导航过程和奖赏获取过程。学习阶段平均划分成8份。利用可驱动微型电极同步记录海马CA1区与OFC的局部场电位（LFP）。通过计算功率谱密度分析各脑区Theta（6~12 Hz）、Beta（15~30 Hz）、Low gamma（30~60 Hz）和High gamma节律（60~90 Hz）神经活动在不同任务态中的活动强度，并结合相干性、相位锁相值（PLV）和相位-幅值跨频耦合（PAC）分析，探讨海马CA1区与OFC在空间目标导向任务中与学习和记忆相关的作用机制。结果在空间目标导向任务中，OFC各个节律的神经活动在同一任务态中表现出一致性（P>0.05），而海马CA1区在Beta节律和High gamma节律神经活动强度则表现出差异（P<0.05）；相较于奖赏获取过程的任务态，双脑区的高相干性和高锁相值主要出现在目标导航过程中，并且这些同步效应在学习稳定阶段高于学习早期阶段（第1阶段 vs 第8阶段 P<0.01）；相较于学习前的测试时期，学习后的测试时期显示出更强的海马CA1区-Theta相位与OFC-Low gamma幅值跨频耦合（P<0.05）。结论空间目标导向任务中，对目标路径的学习与记忆的巩固需要海马CA1区与OFC的同步参与。此外，海马CA1区与OFC之间以跨频耦合方式在奖赏位置短期记忆的维持中发挥重要作用。

关键词: 目标导向任务, 海马CA1, 眶额叶皮质, 神经节律

Abstract:

Objective To investigate the neural mechanisms of rhythmic activity in the hippocampal CA1 region and orbitofrontal cortex (OFC) during a spatial goal-directed task. Methods Four long-Evans rats were trained to perform a spatial goal-directed task in a land-based water maze (Cheese-board maze). The task was divided into 5 periods: Pre-test, Pre-sleep, Learning, Post-sleep, and Post-test. During the Learning phase, the task was split into two goal navigation and two reward acquisition processes with a total of 8 learning stages. Local field potentials (LFP) from the CA1 and the OFC were recorded, and power spectral density analysis was performed on Theta (6-12 Hz), Beta (15-30 Hz), Low gamma (30-60 Hz), and High gamma (60-90 Hz) bands. Coherence, phase-locking value (PLV), and phase-amplitude cross coupling (PAC) were used to assess the interactions between the CA1 and the OFC during learning and memory. Results During the task training, the rats showed consistent rhythms of OFC neural activity across the task states (P>0.05) while exhibiting significant changes in Beta and High gamma rhythms in the CA1 region (P<0.05). Coherence and PLV between the CA1 and the OFC were higher during goal navigation, especially in the stable learning phase (Stage 8 vs Stage 1, P<0.01). The rats showed stronger cross-frequency coupling between CA1-Theta and OFC-Low gamma in the Post-test phase than in the Pre-test phase (P<0.05). Conclusion Learning and memory consolidation in goal-directed tasks involve synchronized activity between the CA1 region and the OFC, and cross-frequency coupling plays a key role in maintaining short-term memory of reward locations in rats.

Key words: goal-directed task, hippocampal CA1, orbitofrontal cortex, neural rhythms

唐令苇, 李佳松, 徐海兵. 海马CA1区与眶额叶皮质的神经节律同步活动参与大鼠空间目标导向任务中的学习与记忆巩固[J]. 南方医科大学学报, 2025, 45(3): 479-487.

Lingwei TANG, Jiasong LI, Haibing XU. Synchronized neural rhythms in rat hippocampal CA1 region and orbitofrontal cortex are involved in learning and memory consolidation in spatial goal-directed tasks[J]. Journal of Southern Medical University, 2025, 45(3): 479-487.

图/表 6

图1 空间目标导向任务的行为表现

Fig.1 Performance of the rats in the spatial goal-directed task. A: Trajectory in the task. This task was divided into 5 periods, and the learning period was further divided into 8 stages. The two orange dots represent two novel reward positions; the two gray dots represent two old reward positions. B: Learning performance was assessed based on the distance of each stage (Stage 1 vs Stage 8, ***P<0.005). C: Memory performance was evaluated based on the number of times that the rats entered the old and novel reward positions during the Pre-test and Post-test, respectively (**P<0.01, ***P<0.005).

图2 海马CA1区和OFC电极埋植

Fig.2 Hippocampal CA1 and OFC tetrodes placement. A: An example of tetrode trajectories from lw016. The arrowhead indicates the end of tetrodes. B: Tetrode positions in the 4 rats. Orange dot: lw016; green dot: lw015; blue dot: js001; red dot: lw014. Numbers represent the distance from the bregma.

图3 海马CA1区和OFC神经节律在不同任务态中的响应差异

Fig.3 Differences in neural rhythm responses between the hippocampal CA1 and OFC in different task states. A: The task state was divided into goal navigation process (S-P1 and P1-P1) and reward acquisition process (P1 and P2). B: Distribution of power across 1-100 Hz. C: Differences in power strength of different rhythms across different processes. D: Comparison of power between reward (average of two novel positions) and non-reward (average of two old positions). *P<0.05, ***P<0.005.

图4 海马CA1区和OFC 的相干性

Fig.4 Coherence of hippocampal CA1 region and the OFC. A: Distribution of coherence across 1-100 Hz. B: Coherence in two goal navigation processes, two reward acquisition processes, and non-reward processes. C: The distribution of coherence across learning phases. D: Comparison of coherence differences in Theta and Beta rhythms during Stage 1 and Stage 8 in two goal navigation processes (**P<0.01, ***P<0.005).

图5 海马CA1区与OFC的相位锁相

Fig.5 Phase locking of hippocampal CA1 and the OFC. A: Distribution of phase locking across the learning phases. B: Comparison of phase locking differences in Theta and Beta rhythms during Stage 1 and Stage 8 in the two goal navigation processes (***P<0.005).

图6 海马CA1区和OFC在长期记忆和短期记忆中的神经活动

Fig.6 Neural activity in the hippocampal CA1 region and the OFC during long-term memory and short-term memory. A: Distribution of power across 1-100 Hz. Dashed line represents Pre-test; solid line represents Post-test. B: Distribution of power across 1-100 Hz. C: Phase-amplitude coupling in Pre-test and Post-test. Y-axis represents the data of OFC in the 15-90 Hz range; X-axis represents the data of CA1 in the Theta rhythm. The color map indicates the phase-amplitude coupling value. The area between the two dashed lines represents the Low gamma rhythm. D: Hippocampal CA1 Theta phase-OFC Low gamma amplitude cross-coupling in the Post-test was greater than in the Pre-test (*P<0.05).

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