Munn Robert G K, Tyree Susan M, McNaughton Neil, Bilkey David K
Department of Psychology, University of Otago Dunedin, New Zealand ; Department of Neurobiology, Stanford University Stanford, CA, USA.
Department of Psychology, University of Otago Dunedin, New Zealand.
Front Behav Neurosci. 2015 Mar 11;9:61. doi: 10.3389/fnbeh.2015.00061. eCollection 2015.
The hippocampal formation plays a critical role in the generation of episodic memory. While the encoding of the spatial and contextual components of memory have been extensively studied, how the hippocampus encodes temporal information, especially at long time intervals, is less well understood. The activity of place cells in hippocampus has previously been shown to be modulated at a circadian time-scale, entrained by a behavioral stimulus, but not entrained by light. The experimental procedures used in the previous study of this phenomenon, however, necessarily conflated two alternative entraining stimuli, the exposure to the recording environment and the availability of food, making it impossible to distinguish between these possibilities. Here we demonstrate that the frequency of theta-band hippocampal EEG varies with a circadian period in freely moving animals and that this periodicity mirrors changes in the firing rate of hippocampal neurons. Theta activity serves, therefore, as a proxy of circadian-modulated hippocampal neuronal activity. We then demonstrate that the frequency of hippocampal theta driven by stimulation of the reticular formation also varies with a circadian period. Because this effect can be observed without having to feed the animal to encourage movement we were able to identify what stimulus entrains the circadian oscillation. We show that with reticular-activated recordings started at various times of the day the frequency of theta varies quasi-sinusoidally with a 25 h period and phase-aligned when referenced to the animal's regular feeding time, but not the recording start time. Furthermore, we show that theta frequency consistently varied with a circadian period when the data obtained from repeated recordings started at various times of the day were referenced to the start of food availability in the recording chamber. This pattern did not occur when data were referenced to the start of the recording session or to the actual time of day when this was not also related to feeding time. This double dissociation demonstrates that hippocampal theta is modulated with a circadian timescale, and that this modulation is strongly entrained by food. One interpretation of this finding is that the hippocampus is responsive to a food entrainable oscillator (FEO) that might modulate foraging behavior over circadian periods.
海马结构在情景记忆的形成中起着关键作用。虽然记忆的空间和情境成分的编码已得到广泛研究，但海马体如何编码时间信息，尤其是在长时间间隔下，人们了解较少。此前研究表明，海马体中位置细胞的活动在昼夜节律时间尺度上受到调节，由行为刺激驱动，但不受光线驱动。然而，此前对这一现象的研究中所使用的实验程序必然混淆了两种替代的驱动刺激，即对记录环境的暴露和食物的可获取性，使得无法区分这些可能性。在此，我们证明，在自由活动的动物中，海马脑电θ波频段的频率随昼夜节律周期变化，且这种周期性反映了海马神经元放电频率的变化。因此，θ波活动可作为昼夜节律调节的海马神经元活动的指标。然后，我们证明，由网状结构刺激驱动的海马θ波频率也随昼夜节律周期变化。由于在无需喂食以促使动物活动的情况下就能观察到这种效应，我们得以确定是何种刺激驱动了昼夜节律振荡。我们发现，在一天中的不同时间开始进行网状激活记录时，θ波频率以25小时周期呈准正弦变化，且当以动物的常规喂食时间为参照时相位对齐，而不是以记录开始时间为参照。此外，我们还表明，当将从一天中不同时间开始的重复记录所获得的数据以记录室中食物可获取的开始时间为参照时，θ波频率始终随昼夜节律周期变化。当数据以记录时段的开始时间或与喂食时间无关的实际时间为参照时，这种模式并未出现。这种双重解离表明，海马θ波受昼夜节律时间尺度调节，且这种调节受食物强烈驱动。这一发现的一种解释是，海马体对一种可能在昼夜节律周期内调节觅食行为的食物可驱动振荡器（FEO）有反应。
