Table 1 Animal findings regarding theta-gamma coupling (TGC)
Authors & Year of publication | Subjects | Measure | Region of brain examined | Task performed / behavior during measurement | Relevant findings | Conclusions |
|---|---|---|---|---|---|---|
Studies featuring memory-related tasks | ||||||
i. Tort et al. (2008) [80] | 6 male Sprague–Dawley rats | iEEG | Striatum, hippocampus | T-maze | - Theta phase modulated high frequency (80-120Hz) but not low frequency (30-60Hz) gamma in striatum - TGC between low and high gamma power and theta phase in hippocampus - TGC strongest during decision making portions of task - Striatal theta phase modulated hippocampal high gamma power | - Low and high frequency gamma may represent distinct physiological processes - TGC phase-amplitude coupling likely related to engagement of cognitive processes across varying time scales |
ii. Tort, Komorowski, Manns, Kopell, & Eichenbaum (2009) [81] | 6 male Long-Evans rats | iEEG | Hippocampus (CA3) | - Freely behaving - Item-context learning task | - Theta phase modulated low gamma power in CA3 during free behavior - TGC in CA3 increased during learning and remained high during overtraining sessions - Strength of TGC predicted mean performance accuracy | TGC important to memory processing |
iii. Shirvalkar, Rapp, & Shapiro (2010) [82] | 6 male Long-Evans rats | iEEG | Hippocampus | Matching-to-place task (six-arm radial water maze) | - Power-power TGC increased during retrieval as compared to exploration (encoding) - Power-power TGC higher for successful versus unsuccessful recall - Strength of TGC predicted memory performance, while indices of theta or gamma power alone did not | Power-power TGC in hippocampus is important to memory-dependent behavior |
iv. Belluscio, Mizuseki, Schmidt, Kempter, & Buzsáki (2012) [60] | 6 male Long-Evans rats | iEEG | Hippocampus (CA1 pyramidal cells) | - Maze exploration - REM sleep | - Phase-phase and phase-amplitude TGC | TGC aids in coordinating neuronal spiking across multiple time scales, potentially helpful in transfer of information and plasticity dependent upon spike timing |
v. Cabral et al. (2014) [83] | 8 NR1-KO mice (“knockouts” lacking NR1 NMDAR subunit in principal CA1 neurons), 7 littermate controls | iEEG | Hippocampus (dorsal CA1) | Five-armed “starmaze” | - Control mice showed increased TGC between theta phase and high-gamma amplitude for place-strategy/allocentric trials and increased TGC between theta phase and low-gamma amplitude during sequence-strategy/egocentric trials - Excess high and low gamma observed in knockout mice | - Preferred frequency of gamma in TGC associated with spatial WM dependent on strategy used - Dynamic strategy switching is disrupted by NMDAR disruption |
vi. Igarashi, Lu, Colgin, Moser, & Moser (2014) [84] | 17 male Long-Evans rats | iEEG | Entorhinal cortex (medial and lateral, layer III), hippocampus (CA1) | Odor-place association task | - Odor-place learning was accompanied by increased phase-amplitude TGC in CA1 during odor-sampling (retrieval) - Phase-amplitude TGC was observed in lateral EC from beginning of task - Gamma (20-40Hz) power in both regions was unaltered | - TGC in hippocampus important to retrieval of learned memories - Learning associated with more extensive coupling of already-existing gamma rhythms |
vii. Nishida, Takahashi, & Lauwereyns (2014) [85] | 4 male Wistar/ST rats | iEEG | Hippocampus (CA1) | Memory-guided spatial alternation task | Modulation of gamma-activity by theta phase strengthened overall from beginning to end of session | Increase in TGC may reflect plasticity of CA1-CA3/C A1-EC network, suggestive of optimized communication between these areas |
xiii. Schomburg et al. (2014) [57] | 9 male Long-Evans, 3 male Sprague–Dawley rats | iEEG | Hippocampus, entorhinal cortex | - Linear track - T-maze - Open field - REM Sleep | - Strong TGC between theta phase and gamma power in hippocampus during memory recall - Gamma amplitude also modulated by theta phase in EC - Preferred theta phase dependent upon from where input is being received | Temporal coordination of activity in entorhinal-hippocampus complex primarily supported by theta- and low-frequency gamma activity |
ix. Takahashi, Nishida, Redish, & Lauwereyns (2014) [86] | 4 male Wistar/ST rats | iEEG | Hippocampus (CA1) | Memory-guided spatial alternation task | Gamma-amplitudes in CA1 were phase-locked to theta during a “fixation” period prior to task performance - Preferred theta-phase differed between high- (60–90 Hz) and low- (30–45 Hz) gamma - low-gamma activity increased with a concurrent decrease in high-gamma activity towards the end of the fixation period | High-gamma activity associated with externally cued information processing, low-gamma with internally generated information processing |
x. Trimper, Stefanescu, & Manns (2014) [87] | 6 male Long-Evans rats | iEEG | Entorhinal cortex | Novel object recognition memory task | - Increased theta-high-gamma phase-amplitude coupling in the hippocampi of rats exploring novel objects - Gamma-gamma phase synchrony between CA3 and CA1 LFPs that varied with relative theta- phase and was greatest for objects subsequently remembered | TGC associated with memory processing, but differentially dependent on frequency of gamma activity |
xi. Siegle & Wilson (2014) [88] | Male parvalbumin-Cre (PV-Cre) heterozygote mice | iEEG | Hippocampus | T-maze | - High-gamma modulated by theta-phase during T-maze performance - Optogenetic stimulation of inhibitory interneurons at trough of theta improved task performance during retrieval, while stimulation at theta peaks improved performance during encoding | - Encoding and retrieval processes occur at different preferential theta phases - Phase-specific inhibition may reduce the response to task-irrelevant inputs |
Studies featuring free exploration, sleep or anesthetization | ||||||
xii. Buzsáki, Leung, & Vanderwolf (1983) [53] | 43 male Long Evans rats | iEEG | Hippocampus | - Activity wheel - Immobility | - Fast EEG (gamma: 25-70Hz) as well as interneuron spiking superimposed upon and modulated by theta phase - More prominent in activity than immobility | Slow activity (theta) may be generated through feed-forward inhibition from septum and direct excitation from entorhinal cortex |
xiii. Soltesz & Deschenes (1993) [89] | Male and female Sprague Dawley rats | iEEG | Hippocampus (CA1, CA3) | Ketamine-xylazine anesthesia | - Injection of Cl− ions into pyramidal cells brought on high frequency (25-50Hz) oscillation modulated at theta-frequency | - Fast oscillations generated by Cl− dependent GABAA receptors - Theta modulation of fast oscillation in hippocampus likely arises through interaction between cholinergic and GABAergic neurotransmitter systems |
xiv. Bragin et al. (1995) [90] | 45 male and female Sprague–Dawley rats | iEEG | Hippocampus (dentate hilus) | - Freely behaving - Immobility - REM Sleep | - Prominent theta-phase to gamma-amplitude coupling, particularly in dentate hilus region, during activity and REM sleep | - TGC due to reciprocal connections between interneurons, hilar mossy cells and CA3 pyramidal cells |
xv. Chrobak & Buzsáki (1998) [91] | 19 Sprague Dawley rats | iEEG | Entorhinal cortex (layers II & III), Hippocampus | Freely behaving | - Nesting of gamma oscillations within theta oscillations in the entorhinal cortex and hippocampus - Neuronal spiking in entorhinal cortex in phase with the local, nested gamma oscillations - Synchronization between theta-gamma rhythms in entorhinal cortex and dentate hilar region of hippocampus | Systematic phase-locking of gamma oscillations to nesting theta oscillations is necessary for communication within perforant pathway |
xvi. Buzsáki et al. (2003) [92] | 13 hybrid (C57B6/J & 129S6/SvEvTac) and 3 inbred (C57B6/J) mice | iEEG | Hippocampus (CA1 pyramidal layer, dentate gyrus) | - Freely behaving - Immobile awake - Sleeping | Gamma, interneurons and pyramidal cells all phase-locked to concurrent theta rhythm during free behavior | - Mouse brain is similar to rat brain - Interneurons critical to gamma generation |
xvii. Csicsvari, Jamieson, Wise, & Buzsáki (2003) [93] | 12 male Sprague–Dawley rats | iEEG | Hippocampus (CA1, CA3, granule cell layers) | - Freely behaving - Immobility - Slow wave sleep - REM sleep | - Gamma power varied with theta phase when theta present but irregularly otherwise - Gamma field power greater in CA1 during theta-associated behaviors - Gamma CSD power greater in granule cell layer during theta-associated behaviors | Concurrent theta is not necessary for gamma oscillation, but theta enhances and modulates gamma when present |
xviii. Hentschke, Perkins, Pearce, & Banks (2007) [94] | B6129SF2⁄J wild-type mice | iEEG | Hippocampus (CA1, all laminae) | - Freely behaving - Immobile awake | - Phase-amplitude TGC during exploration and immobility, highest around hippocampal fissure - Significantly decreased by injection of atropine, a muscarinic antagonist | Phase-amplitude TGC in CA1 influenced by neurons with muscarinic receptors |
xix. Sirota et al. (2008) [95] | 28 rats, 11 mice | iEEG | Hippocampus, neocortex | - Active (n = 28 rats, 11 mice) - Anesthetized (n = 27 rats) | - Phase-phase coupling between hippocampal theta rhythms and gamma oscillations in multiple regions of neocortex, including prefrontal cortex and primary sensory areas | TGC between hippocampus and neocortex means for transfer of information from neocortex to hippocampus |
xx. Wulff et al. (2009) [96] | PV-Δγ2 mice (mice with GABAA receptor γ2 subunit ablated from parvalbumin-positive interneurons in hippocampus); normal litter-mates as controls | iEEG | Hippocampus | Freely behaving | - Phase-amplitude TGC nearly three times as weak in PV-Δγ2 as control mice | PV+ neurons involved in coupling of theta to gamma activity |
xxi. Quilichini, Sirota, & Buzsáki (2010) [97] | 39 male Sprague–Dawley rats | iEEG | Entorhinal cortex (layers II, III, V) | - Anesthetized | - Gamma (including high frequency) power modulated by theta phase in all layers - Different theta phase preferences from layer to layer | Gamma activity can be generated locally in individual EC layers and relate to phase of hippocampal theta activity |
xxii. De Almeida, Idiart, Villavicencio, & Lisman (2012) [59] | Rats | iEEG | Entorhinal cortex (grid cells) | - Open field exploration - Traversal of linear track | - Phase precession observed in grid cells with two varying “modes”: inbound (firing occurs as rat approaches center of place field) and outbound (firing occurs as rat leaves center) | Grid cells have different modes which account for upcoming locations versus those recently passed, serving both storage and predictive functions of hippocampus |
xxiii. Caixeta, Cornélio, Scheffer-Teixeira, Ribeiro, & Tort (2013) [65] | 8 male Wistar rats | iEEG | Left hippocampus | - Open field exploration - Saline injection - Ketamine injection | - Ketamine increased motor activity and gamma power - Prominent phase-amplitude coupling between theta- and high-gamma (60–100Hz) as well as high frequency oscillations (HFO; 110–160Hz) pre-ketamine injection - Theta-HFO coupling increased with ketamine, while theta-gamma coupling increased at the lowest dosage but markedly disturbed at the highest dosage | Some symptoms of schizophrenia may be explained by aberrant TGC and/or theta-HFO coupling |
xxiv. Newman, Gillet, Climer, & Hasselmo (2013) [98] | 6 male Long-Evans rats | iEEG | Entorhinal cortex (medial) | - Lap-running on circular track - With and without scopolamine injection | - Robust phase-power TGC for both low- (20-40Hz) and high- (60–120Hz) gamma - Scopolamine selectively reduced high gamma power at peak of theta | - Encoding and retrieval may occur at peak and through of theta, respectively - Acetylcholine influences balance between encoding and retrieval processes |
xxv. Pernía-Andrade & Jonas (2014) [99] | Wistar rats | Whole cell recording | Hippocampal (dentate gyrus) granule cells | - Anesthetized - Free exploration | - EPSCs coherent with LFP theta oscillations; IPSCs coherent with LFP gamma oscillations - Action potentials phase locked to theta-gamma oscillations in LFP | - TGC in dentate gyrus may reflect inhibitory gamma currents phase locked to theta currents and initiated by excitation from the entorhinal cortex - Compound signal may serve as temporal reference signal for encoding in granule cells |
xxvi. Yamamoto, Suh, Takeuchi, & Tonegawa (2014) [100] | MECIII-TeTX MT Mice (allow for reversible silencing of synaptic transmission of MEC layer III pyramidal cells), control litter-mates | iEEG | Hippocampus (CA1), entorhinal cortex (medial, layer III) | Open field exploration | - High-frequency and low-frequency gamma modulate to different phases of theta | High-frequency gamma contributes uniquely to WM function |
In vitro or isolate studies | ||||||
xxvii. Cunningham, Davies, Buhl, Kopell, & Whittington (2003) [101] | Male Sprague–Dawley rats | iEEG | Hippocampus, entorhinal cortex | In vitro | - Amplitude of field gamma activity modulated at theta frequency in presence of kainate receptor activation | EC can generate intrinsic theta activity |
xxviii. Goutagny et al. (2013) [102] | TgCRND8 mice (develop at 3 months of age amyloid-beta plaques typical of Alzheimer’s disease and accompanied by similar cognitive decline) | iEEG | Hippocampus | N/A (hippocampal isolate) | - Some TgCRND8 showed alterations in phase-amplitude TGC prior to accumulation of amyloid-beta plaques or cognitive decline) - Exclusive to theta coupling with fast gamma, not slow gamma | Declines in TGC are early electrophysiological indicators of hippocampal network dysfunction |
xxix. Pastoll, Solanka, van Rossum, & Nolan (2013) [103] | Adult Thy1-ChR2-YFP line 18 mice | iEEG | Entorhinal cortex (medial) | N/A (isolated brain slices, though with simulated movement) | - Optogenetic stimulation of medial entorhinal cortex at theta frequency sufficient to produce nested gamma activity with both phase and amplitude coupled to theta phase - Nested gamma is mediated by feedback inhibition | Local medial entorhinal cortex circuit produces TGC with “clock-like” (p. 153) consistency; coupled signals may serve as temporal references for other neuronal computations |
Primate studies | ||||||
xxx. Lakatos et al. (2005) [104] | 4 male macaque monkeys | iEEG | Primary auditory cortex | Passive listening task | Spontaneous gamma-activity found to fluctuate at theta-frequency, and theta-activity found to subsequently fluctuate at delta frequency | Oscillatory activity is organized in a hierarchical manner, not exclusively limited to gamma and theta activity |
xxxi. Voloh, Valiante, Everling, & Womelsdorf (2015) [105] | 2 macaque monkeys | iEEG | Medial and lateral PFC (anterior cingulate cortex) | Attention task | - Theta-phase to gamma-amplitude TGC between various sites in ACC and PFC during task performance, but not before errors | TGC essential to integration of varied and distributed activities, including attention, in neural networks |