Hippocampal theta frequency, novelty, and behavior

Sambeth, Meeter, and Blokland (2009) raise several points regarding our recent article on the effect of environmental novelty on theta frequency (Jeewajee et al., 2008b). These can be summarized as follows, using Sambeth et al., (2009) enumeration. (1) We should not have used food deprived rats, as food deprivation affects acetylcholine (ACh) levels, about which ‘‘specific assumptions were made’’; (2a) We found no effects on theta power, which they find surprising; (2b) They found no effect of novelty on theta frequency in a recent experiment, failing to replicate our finding; (3) The Fourier analysis we used to estimate peak theta frequency requires more than 5s of data for the accuracy presented; (4a) Two coexisting frequencies would result in two peaks in the power spectrum, bringing into question our proposed interpretation for our results; (4b) They found no difference in theta frequency between ‘passive’ and ‘active’ behaviors, bringing into question the need to control for running speed (a feature of our analysis, but not theirs). Let us start with Point 1. We reported an experimental result: a reduction of theta frequency induced by environmental novelty. We made no assumptions about ACh. However, we did suggest a speculative interpretation relating our findings to the previous identification of two components of the process of theta generation: one related to arousal and cholinergically mediated, the other related to movement and cholinergically independent. Each component, when isolated, is associated with different frequencies, see (Buzsaki, 2002; O’Keefe, 2006) for reviews. We suggested that environmental novelty might cause a change in the relative influence of these two components in producing theta, not that both frequencies coexist (Point 4a)! But yes, we agree on the need for further research into the generation of theta, and the effects of environmental novelty upon it, see e.g., (Blair et al., 2008; Burgess, 2008). How about the effects of novelty on theta frequency and theta power (Point 2)? First, we specifically did not look for, or report, the presence or absence of any effects of novelty on theta power. Unlike theta frequency, theta power will vary with electrode location within the hippocampal formation, and this was not systematically controlled in our study. Second, it is crucial to control for behavioral differences which might themselves produce an effect. In this regard, it has been clear for some time that walking and rearing produces higher theta frequency than manipulatory and head movements (Vanderwolf, 1969, Fig. 3 and pp 409–410). More recent work demonstrates increased theta power for rearing and moving compared to grooming or immobility (Young and McNaughton, 2009, see Fig. 9), as also shown by (Sambeth et al., 2009; see their Fig. 1). In addition, there is a strong relationship between running speed and both theta frequency (Rivas et al., 1996; Slawinska and Kasicki, 1998; Jeewajee et al., 2008a), see Fig. 1 and theta power (Rivas et al., 1996). Thus, an immediate potential confound is that environmental novelty elicits increased rearing (Anderson et al., 2006; Lever et al., 2006; Hunsaker et al., 2008; Wells et al., 2009), and changes in running speed with environmental novelty are explicitly shown in (Jeewajee et al., 2008b). We controlled for these potential confounds by only analyzing data from rats running at over 5 cm/s (ruling out rearing), and accounted for variations in running speed in two ways: covarying out any effects of differences in the median speed of each trial, and also subsampling data from novel and familiar trials so that they had the same median speed. In addition, we attempted to control for nonspecific effects of tiredness, satiation, circadian rhythms etc. by running baseline (familiar) trials before and after novel trials. We have since replicated our finding in a new laboratory on a different site (Wells et al., 2008). Sambeth et al., (2009) do not present sufficient detail to allow understanding of the differences between their study and ours. However, they appear not to have controlled for the effects of differential running speed or rearing frequency, or to have run baseline (familiar) trials before and after novel trials. Increased rearing frequency or running speed could potentially explain why they report a higher theta frequency in novelty relative to familiarity than we did. Previous reports of increased theta power during novelty typically note markedly different behavior during Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, United Kingdom; 2 Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Department of Cell and Developmental Biology, University College London, London, United Kingdom; UCL Institute of Neurology, United Kingdom *Correspondence to: Neil Burgess, Institute of Cognitive Neuroscience, University College London, London, United Kingdom. E-mail: n.burgess@ ucl.ac. ak or Colin Lever, Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, United Kingdom. E-mail: c.lever@leeds.ac. uk. Accepted for publication 1 December 2008 DOI 10.1002/hipo.20557 Published online 27 January 2009 in Wiley InterScience (www. interscience.wiley.com). HIPPOCAMPUS 19:409–410 (2009)