e., at different theta phases. Given that there are four to eight gamma cycles nested within a theta cycle, multiple items can be represented in a defined

order. Here, we will first describe the evidence that jointly occurring theta and gamma oscillations can organize information in the way hypothesized in Figure 1B. We will then describe experiments that address Ceritinib the following questions: (1) do the oscillations and their interaction vary with cognitive demands, and do these changes predict behavioral performance? (2) Does interfering with (or enhancing) the oscillations affect function? (3) Are the oscillations used to coordinate communication between brain regions? We then turn to an analysis of the mechanistic role of gamma oscillations in the context of the theta-gamma code.

In the final section, we discuss outstanding issues, notably the relationship of alpha and theta FG-4592 nmr frequency oscillations in cortex and the possibility that the theta-gamma code contributes not only to memory processes, but also to sensory processes. The first indication that theta oscillations have a role in neural coding came from the study of rat CA1 hippocampal place cells. Such cells increase their firing rate when the rat is in a subregion of the environment called the place field; different cells have different place fields (O’Keefe and Dostrovsky, 1971). As the rat crosses the place field of a cell, PAK6 there are generally five to ten theta cycles. On each successive cycle, firing tends to occur with earlier and earlier theta phase (Figure 2A), a phenomenon termed the phase precession (O’Keefe and Recce, 1993; Skaggs et al., 1996). These and related results (Lenck-Santini et al., 2008; Pastalkova et al., 2008) suggest that the hippocampus uses a code in which theta phase carries

information. Further analysis showed that CA1 place cells fire at a preferred phase of the faster gamma oscillations (Figure 2B; Senior et al., 2008). Thus, during a given theta cycle, firing will tend to occur at a preferred theta phase and at a preferred gamma phase. If a place cell fires at a particular phase during a theta cycle (i.e., in a particular gamma cycle), other place cells representing different information presumably fire at other theta phases, collectively forming a multipart message. The ability to record simultaneously from >100 cells (Wilson and McNaughton, 1993) has made it possible to directly observe such messages. As illustrated in Figure 3, during an individual theta cycle, different place cells fire in a temporal sequence. These sequences are called “sweeps” because the firing order corresponds to the cells’ place field centers along the track (Gupta et al., 2012; see also Dragoi and Buzsáki, 2006; Harris et al., 2003; Skaggs et al., 1996). Such data show directly that different cells representing different information (i.e., positions) fire at different theta phases.