**Author details**

**5. Why does hippocampal theta amplitude decline?**

al. [38].

16 Electroencephalography

Hippocampal theta power is affected by the activity of cholinergic and γ-aminobutyric acid (GABA) neurons of the medial septal/diagonal band area [44]. Monmaur and Breton [50] demonstrated that theta activity increases when the cholinergic agonist, carbachol, is injected into the intra septum in freely moving rats. In addition, Sun et al. [51] reported that hippocampal theta activity is abolished by the GABA antagonist bicuculline. Thus, we propose that the transient decrease in hippocampal theta activity during compound stimulus learning in the negative patterning task is induced by the activity of septal cholinergic or GABAergic neurons, or their interaction. In future studies, the relationship between the negative patterning task and septal cholinergic and/or GABAergic activity should be examined. Because septo-hippocampal GABAergic input to CA1 is essential for the generation of theta waves [52], the transient decrease

**Figure 2.** A comparison of the mean relative hippocampal theta activity between tasks. Panel A shows the relative hippocampal theta power during the 500-ms epochs between the negative patterning and simple discrimination task groups. A group (negative patterning task and simple discrimination task groups) × stage (early, middle, and late) ANOVA for hippocampal theta activity during a 500-ms epoch in the nonRFT showed a significant interaction (*F*(2,20) = 6.12, *p* < 0.05). Multiple comparisons revealed that hippocampal theta power decreased during the late stage in the negative patterning task compared to the simple discrimination task group (*p* < 0.05; \*: *p* < 0.05). Hippocampal theta power during the 500 ms nonRFT correlated with the discrimination rate in the negative patterning task (*r* = −0.70, *p* < 0.05; panel B) but not the simple discrimination task (*r* = −0.06, *p* = n.s; panel C). This figure was referred to Sakimoto et

Yuya Sakimoto\* and Dai Mitsushima

\*Address all correspondence to: y-saki@yamaguchi-u.ac.jp

Department of Physiology, Graduate School of Medicine, Yamaguchi University, Minami-Kogushi, Ube, Japan
