Hippocampal theta frequency and novelty

Various studies indicate that the hippocampus plays an essential role in novelty detection. In particular, contextual/spatial changes are detected by the hippocampus, presumably by comparing incoming information with stored information (e.g., Knight, 1996). However, the exact nature and processes underlying hippocampal novelty detection remain elusive. One important mechanism that may underlie hippocampal novelty detection is hippocampal theta activity. In a recent paper, Jeewajee et al. (2008) proposed a link between the hippocampal theta and the detection of novel contexts. Four food-deprived rats were equipped with hippocampal electrodes and exposed to familiar and novel environments in which they were searching for food. The authors found that the peak hippocampal theta frequency dropped (by about 0.6 Hz) when the rats were tested in a novel environment. They argued that the change in theta frequency may function as a novelty signal because hippocampal theta frequency is the same in the whole hippocampus (Buzsaki, 2002) and suggested that this reduction in the theta frequency would have implications for memory encoding. The authors speculate that novelty leads to an altered weighing between a high-frequency locomotionrelated theta and a low-frequency theta dependent on acetylcholine release. Although the study of Jeewajee et al. (2008) provides novel insights into the mechanisms underlying hippocampal novelty detection, some points suggest that it may be too early to accept their conclusions at face value. The first point is related with the design of study, in which fooddeprived rats were used. During the recording sessions, rats were foraging grains of sweetened rice which were thrown in the box every 30 s. Several studies have indicated that food consumption and reinforcement increase hippocampal acetylcholine (ACh) levels (Ghiani et al., 1998; Iso et al., 1999). Since specific assumptions were made with respect to hippocampal ACh levels and novelty-induced increase in ACh and an increase in cholinergic input to the hippocampus affects hippocampal theta activity (Givens and Olton, 1995; Podol’skii et al., 2001), the results of this experiment may have been distorted by the foraging. Therefore, it would have been more appropriate to expose nondeprived subjects to familiar and novel environments. This may be a more proper setting to detect changes in theta in relation to novelty per se. Secondly, the authors found the effects of novelty on peak theta frequency, but not on theta power. This is at odds with previous findings in the literature. Jeewajee et al. relate their findings of novelty-induced theta peak frequency reductions to a study of Givens and Olton (1995). In this study, carbachol injections into the medial septum, which increases hippocampal ACh levels, did not affect the theta peak. Only in combination with scopolamine (given intraperitoneal), the peak theta frequency was reduced by carbachol injections. Two other studies of this group (Givens and Olton, 1994; Markowska et al., 1995) also examined the effects of intraseptal injection of cholinergic drugs. These studies indicate that scopolamine (i.e., lower hippocampal ACh) reduces theta power and increases peak frequency. Further, the muscarinic agonist oxotremorine reduced peak frequency and increased theta power. In all these studies, decreases and increases in theta power were very robust, while effects on peak frequency were smaller and less consistent. The decrease in peak frequency found by Jeewajee et al. is thus in line with previous data, but their lack of effects of novelty on theta power is puzzling. Indeed, we recently conducted a study in which rats were exposed to novel and familiar environments. We found that theta power was affected by novelty rather than theta frequency (see Fig. 1). The third point of caution relates to the analysis of theta frequency. Jeewajee et al. showed changes in theta frequency as accurate as 0.2 Hz. Frequency resolution, the accuracy of different frequency steps that can be analyzed, depends on the length of a measurement and the sample rate; the longer and higher, respectively, the better will be the resolution. In the study of Jeewajee et al., the sample rate that was used to record the EEG was 250 Hz. With these settings, epochs of 5 s are needed to obtain a frequency resolution at a 0.2 Hz level. Unfortunately, the authors did not provide any specific information on how long animals usually spent running at speeds over 5 cm/s and their restriction for the acceptance of an epoch into Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, The Netherlands; Department of Cognitive Psychology, Vrije Universiteit Amsterdam, The Netherlands *Correspondence to: Arjan Blokland, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, The Netherlands. E-mail: a.blokland@psychology.unimaas.nl Accepted for publication 17 November 2008 DOI 10.1002/hipo.20541 Published online 11 February 2009 in Wiley InterScience (www. interscience.wiley.com). HIPPOCAMPUS 19:407–408 (2009)