Graduate Program in Neuroscience, The University of Western Ontario, London, Canada N6A 5C1.
Hippocampus. 2012 Apr;22(4):914-25. doi: 10.1002/hipo.20955. Epub 2011 May 3.
The vestibular system has been suggested to participate in spatial navigation, a function ascribed to the hippocampus. Vestibular stimulation during spatial navigation activates a hippocampal theta rhythm (4-10 Hz), which may enhance spatial processing and motor response. We hypothesize that a cholinergic, atropine-sensitive theta is generated during passive whole-body rotation in freely behaving rats. Hippocampal EEGs were recorded by implanted electrodes in CA1 while rats were rotated on a vertical axis, for a minute or longer, at different angular velocities. Rotation induced a continuous hippocampal theta rhythm while the rat was immobile, in both light and dark conditions. Theta peak frequency showed a significant increase during high (50-70 rpm) as compared with a lower (20-49 rpm) rotational velocity. Rotation-induced theta was abolished by muscarinic receptor antagonist atropine sulfate (50 mg/kg i.p.) but not by atropine methyl nitrate (50 mg/kg i.p.), which did not pass the blood-brain barrier. Theta was attenuated in rats in which cholinergic neurons in the medial septum (MS) were lesioned with 192 IgG-saporin (0.14 μg in 0.4 μl), as confirmed by depletion of MS cells immunoreactive to choline acetyltransferase and an absence of acetylcholinesterase staining in the hippocampus. Bilateral lesion of the vestibular receptors by sodium arsanilate (30 mg in 0.1 ml, intratympanically) also attenuated the rotation-induced theta rhythm. In intact rats, field excitatory postsynaptic potentials (fEPSPs) in CA1 evoked by commissural stimulation were smaller during walking or rotation as compared with during immobility. Modulation of fEPSP was absent following atropine sulfate in intact rats and in 192 IgG-saporin lesion rats. In summary, this is the first report of a continuous atropine-sensitive hippocampal theta in the rat induced by vestibular stimulation during rotation, and accompanied by cholinergic modulation of hippocampal synaptic transmission. Vestibular-activated septohippocampal cholinergic activity could be an important component in sensorimotor processing and spatial memory.
前庭系统被认为参与空间导航，这一功能归因于海马体。在空间导航过程中刺激前庭会激活海马体θ节律（4-10 Hz），这可能增强空间处理和运动反应。我们假设，在自由活动的大鼠进行全身被动旋转时，会产生一种胆碱能、阿托品敏感的θ节律。通过植入 CA1 中的电极记录海马 EEG，当大鼠在不同角速度下沿垂直轴旋转一分钟或更长时间时进行旋转。旋转会在大鼠处于静止状态时在明亮和黑暗条件下诱导连续的海马θ节律。与较低（20-49 rpm）旋转速度相比，在较高（50-70 rpm）旋转速度下，θ 峰频率显著增加。旋转诱导的θ节律被毒蕈碱受体拮抗剂硫酸阿托品（50 mg/kg ip）消除，但被不能通过血脑屏障的硝酸甲基阿托品（50 mg/kg ip）消除。用 192 IgG-箭毒（0.4 μl 中 0.14 μg）损伤中隔内侧（MS）中的胆碱能神经元后，旋转诱导的θ节律会减弱，这一点通过 MS 细胞对胆碱乙酰转移酶的免疫反应性减少和海马乙酰胆碱酯酶染色缺失得到证实。经氨基苯砷酸钠（0.1 ml 中 30 mg，鼓室内）双侧损伤前庭受体也会减弱旋转诱导的θ节律。在完整大鼠中，与静止时相比，在行走或旋转时，由联合刺激在 CA1 中诱发的场兴奋性突触后电位（fEPSP）较小。在完整大鼠和 192 IgG-箭毒损伤大鼠中，用硫酸阿托品处理后，fEPSP 的调制缺失。综上所述，这是第一个报道的由旋转过程中前庭刺激引起的、持续的、阿托品敏感的大鼠海马θ节律，伴随着海马突触传递的胆碱能调制。前庭激活的隔海马胆碱能活动可能是感觉运动处理和空间记忆的重要组成部分。
