Abstract
Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments that selectively manipulate phase-specific information processing. Using closed-loop stimulation, we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely behaving mice. This intervention enhanced performance on a spatial navigation task that requires the encoding and retrieval of information related to reward location on every trial. In agreement with prior models of hippocampal function, the behavioral effects depended on both the phase of theta and the task segment at which we stimulated. Stimulation in the encoding segment enhanced performance when inhibition was triggered by the peak of theta. Conversely, stimulation in the retrieval segment enhanced performance when inhibition was triggered by the trough of theta. These results suggest that processes related to the encoding and retrieval of task-relevant information are preferentially active at distinct phases of theta.DOI: http://dx.doi.org/10.7554/eLife.03061.001.
Highlights
Theta oscillations (4–12 Hz) are one of the most prominent rhythms in the mammalian brain (Vanderwolf, 1969; Buzsáki et al, 1983; Colgin, 2013)
Recording in CA1, CA3, and entorhinal cortex (EC) reveals that oscillations in the high gamma range (60–100 Hz) are a signature of enhanced coordination between CA1 and EC, whereas low gamma (25–50 Hz) indicates enhanced coordination between CA3 and EC. These oscillations occur at different phases of theta, and typically on different cycles (Colgin et al, 2009). These results indicate that the balance between the relative influence of the outside world and internal states on hippocampal outputs is strongly modulated as a function of theta phase
We found that triggering inhibition on the peak of theta improved performance when it occurred in the encoding segment of the task, but had no effect in the retrieval segment
Summary
Theta oscillations (4–12 Hz) are one of the most prominent rhythms in the mammalian brain (Vanderwolf, 1969; Buzsáki et al, 1983; Colgin, 2013). Neural activity is highly structured within each cycle of theta, with the firing rates of genetically defined cell types peaking at different phases (Klausberger et al, 2003, 2004, 2005). The organization of activity relative to theta appears to be important for behavior, since the degree to which other regions synchronize to the hippocampal theta rhythm is correlated with spatial decision-making performance (Jones and Wilson, 2005; Sigurdsson et al, 2010). The specific role of theta in guiding behavior remains unclear, due to a lack of studies employing causal interventions with adequate temporal precision to selectively disrupt or enhance activity within this rhythm. We employed a closed-loop approach to target an optogenetic manipulation to particular phases of endogenously generated theta oscillations.
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