Theta–gamma coupling increases during the learning of item–context associations

Abstract

Phase-amplitude cross-frequency coupling (CFC) between theta (4 -12 Hz) and gamma (30 -100 Hz) oscillations occurs frequently in the hippocampus. However, it still remains unclear whether thetagamma coupling has any functional significance. To address this issue, we studied CFC in local field potential oscillations recorded from the CA3 region of the dorsal hippocampus of rats as they learned to associate items with their spatial context. During the course of learning, the amplitude of the low gamma subband (30 -60 Hz) became more strongly modulated by theta phase in CA3, and higher levels of theta-gamma modulation were maintained throughout overtraining sessions. Furthermore, the strength of theta-gamma coupling was directly correlated with the increase in performance accuracy during learning sessions. These findings suggest a role for hippocampal theta-gamma coupling in memory recall.associative memory ͉ brain rhythms ͉ local field potential B rain oscillations have been classically divided into specific frequency ranges associated with multiple cognitive processes (1, 2). Oscillations in these frequency bands may occur simultaneously and can interact with each other (3, 4), suggesting that this coupling may reflect a higher-order representation (5, 6). In one type of interaction, the phase of low-frequency rhythms modulates the amplitude of higher-frequency oscillations (3). This type of cross-frequency coupling (CFC) is called phase-amplitude modulation, and its best known example occurs in the rodent hippocampus between the theta (4-12 Hz) phase and the amplitude of gamma (30-100 Hz) oscillations (6-9). Based on this finding, theoretical work has suggested that gamma and theta oscillations coordinate in support of a neural code (10-15). According to this view, events are represented by distinct neuronal ensembles, each contained within a distinct gamma cycle, and entire episodes are encoded by a succession of event-specific gamma cycles embedded into each theta cycle (12-15). These theories are elegant and appealing, but there is a paucity of evidence linking the existence of theta-gamma coupling to behavior (but see ref. 16). Therefore, it remains unclear whether the hippocampal theta-gamma coupling possesses any functional role (13).Here, we investigated coupling between theta and gamma rhythms as rats learned which of two stimuli was rewarded depending on the environmental context in which the stimuli were presented. Learning in this type of conditional discrimination task depends on hippocampal function (17, 18). On each trial, a rat initially explored one of two environmental contexts, then the two stimuli were placed into different corners of the environment and the rat was required to choose the correct stimulus for that context to receive a reward (Fig. 1A). In our preliminary studies, we found that the initial context exploration period is essential for learning the context-dependent choice. Therefore, we focused on the prominent theta and gamma activity that is prevalent during this period. We fou...

Hippocampal Theta-Phase Modulation of Replay Correlates with Configural-Relational Short-Term Memory Performance: Figure 1.

“…According to an influential computational model (Lisman and Idiart, 1995;Jensen and Lisman, 1998;Lisman, 2010), maintenance is enabled by a cross-frequency coupling of gamma-(30 -80 Hz oscillations) related neural spiking to specific phases of ongoing hippocampal theta oscillations (4)(5)(6)(7)(8). In agreement with this model, theta/ gamma coupling has been observed in relation to sequential (Axmacher et al, 2010) and spatial (Tort et al, 2009) shortterm memory. Fuentemilla et al (2010) investigated theta-coupled periodic replay during short-term memory maintenance using wholehead magnetoencephalographic (MEG) recordings.…”

Altered cross-frequency coupling in resting-state MEG after mild traumatic brain injury

“…Results from recent studies in both animals and humans support a mechanism that oscillations at higher frequencies are often modulated by the phase of slower phase fluctuations (Osipova et al, 2008;Tort et al, 2008Tort et al, , 2009Tort et al, , 2010Cohen et al, 2009a, b;Colgin et al, 2009;Axmacher et al, 2010a, b;Voytek et al, 2010). Important elements of nonlinear coupling across different frequencies reveal different types of CFC, such as phase-amplitude coupling (Tort et al, 2008(Tort et al, , 2009(Tort et al, , 2010Cohen et al, 2009a,b;Colgin et al, 2009;Axmacher et al, 2010a,b), n:m phase locking (Dimitriadis et al, 2015b), and amplitude-amplitude coupling (Hipp et al, 2012;Engel et al, 2013).…”

“…There is ample evidence that the last type of CFC, also called phase-amplitude modulation, occurs very often in both animals and humans in the prefrontal cortices, the hippocampus, and other distributed cortical areas (Osipova et al, 2008;Tort et al, 2008Tort et al, , 2009Tort et al, , 2010Cohen et al, 2009a, b;Colgin et al, 2009;Axmacher et al, 2010a, b;Voytek et al, 2010).…”

Mechanisms underlying memory enhancement in humans

“…Evidence from rodents suggests that theta/gamma coupling could be functionally important for long-term memory processes (Tort, Komorowski, Manns, Kopell, & Eichenbaum, 2009). In this study, as learning of the association between context and food reward location progressed, the animals showed an increase in cross-frequency coupling which the strength of coupling predicting the probability of correct choice.…”

“…Similarly to the present study, a number of human and animal studies have demonstrated a relationship between theta power and coherence, as well as gamma and theta/gamma coupling at both medial temporal lobe and other neocortical sites in relation to information processing (Fell et al, 2001(Fell et al, , 2003Sederberg et al, 2003;Canolty et al, 2006;Tort et al, 2009;Shirvalkar et al, 2010, Colgin et al, 2009). The findings provided here suggest that (1) …”