Dynamic cross-frequency couplings of local field potential oscillations in rat striatum and hippocampus during performance of a T-maze task Adriano B. L. Torta,b,1, Mark A. Kramera, Catherine Thornc,d, Daniel J. Gibsonc,e, Yasuo Kubotac,e, Ann M. Graybielc,e,2, and Nancy J. Kopella,1,2 aDepartment of Mathematics and Center for BioDynamics, Boston University, Boston, MA 02215; bDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035, Brazil; and cMcGovern Institute for Brain Research and Departments of dElectrical Engineering and Computer Science, and eBrain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 Contributed by Nancy J. Kopell, October 21, 2008 (sent for review August 19, 2008) Oscillatory rhythms in different frequency ranges mark different tional T-maze task (14), we asked whether theta phase modulates behavioral states and are thought to provide distinct temporal win- cooccurring high-frequency oscillations in the striatum as well as in dows that coherently bind cooperating neuronal assemblies. How- the hippocampus, and if so whether such cross-frequency effects ever, the rhythms in different bands can also interact with each other, occur between the 2 structures, and whether the phase–amplitude suggesting the possibility of higher-order representations of brain coupling is related to specific behavioral performance. We dem- states by such rhythmic activity. To explore this possibility, we onstrate here that distinct bands of high-frequency oscillations are analyzed local field potential oscillations recorded simultaneously modulated by ongoing low-frequency rhythms, both within and from the striatum and the hippocampus. As rats performed a task across the striatum and hippocampus. We further show that the requiring active navigation and decision making, the amplitudes of strength of these cross-frequency interactions changes dynamically, multiple high-frequency oscillations were dynamically modulated in and differentially, during different epochs of behavioral perfor- task-dependent patterns by the phase of cooccurring theta-band mance requiring decision and action. These findings suggest that the oscillations both within and across these structures, particularly dur- cross-frequency interactions reflect behaviorally relevant simulta- ing decision-making behavioral epochs. Moreover, the modulation neous activation of synchronized striatal and hippocampal memory patterns uncovered distinctions among both high- and low-frequency subbands. Cross-frequency coupling of multiple neuronal rhythms circuits. could be a general mechanism used by the brain to perform network- Results level dynamical computations underlying voluntary behavior. We analyzed the LFP oscillatory activity recorded in the dorsal amplitude modulation ͉ gamma ͉ theta caudoputamen and the CA1 field of the dorsal hippocampus as rats (n ϭ 6) navigated a T-maze in which they turned right or left in response to auditory instruction cues indicating which of the 2 end scillations in neural population voltage activity are universal A Ophenomena (1). Among brain rhythms, theta oscillations in arms was baited with chocolate (14, 15) (Fig. 1 ). In both the local field potentials (LFPs) recorded in the hippocampus are striatum and the hippocampus, theta power increased as the rats prominent during active behaviors (2–5), and these have long been left the start zone, peaked as the animals traversed the maze, and intensively analyzed in the rodent in relation to spatial navigation diminished as the rats approached the goal [Figs. 1 B and C and 2 (6), memory (7), and sleep (8). Theta-band rhythms (4–12 Hz) are A and B and supporting information (SI) Fig. S1]. By contrast, low now known to occur in other cortical (9–12) and subcortical (12–15) gamma power (LG, 30–60 Hz) diminished during the middle of the regions, however, including the striatum (14–17), studied here. task, and high gamma (HG, 60–100 Hz) and high-frequency Gamma oscillations (30–100 Hz) have also received special atten- oscillations (HFO, Ͼ100 Hz) powers increased throughout the tion because of their proposed role in functions such as sensory maze runs (Figs. 1 B and C and 2 A and B and Fig. S1). Notably, binding (18), selective attention (19–21), transient neuronal assem- these modulations in power had different time courses in the 2 bly formation (22), and information transmission and storage structures (see Figs. 1 B and C and 2 A and B and Fig. S1). (23–25). The existence of physiologically meaningful neocortical To determine whether interactions across these frequency ranges oscillations at even higher frequencies, above the traditional gamma occurred, we developed a cross-frequency measure to analyze range, has been reported as well (10, 26–28). In rodents, for phase-to-amplitude modulation in limited-time datasets (modula- example, brief sharp-wave associated ripples (120–200 Hz) appear tion index, see SI Text). This method allowed us to examine in the hippocampal formation during slow wave sleep, immobility phase–amplitude modulation for successive event epochs during and consummatory behavior, characteristically in the absence of the maze runs. Phase-to-amplitude comodulograms were con- theta waves (2, 29). structed by applying this measure to multiple frequency band pairs The oscillatory activities conventionally assigned to different made up of ‘‘phase frequency’’ and ‘‘amplitude frequency’’ bands frequency bands are not completely independent (2–4, 9, 10, 30). stepped through task time (Figs. 1D and 2 C and D and Fig. S2). In one type of interaction, the phase of low-frequency rhythms modulates the amplitude of higher-frequency oscillations (9, 10, NEUROSCIENCE 30). For example, theta phase is known to modulate gamma power Author contributions: A.M.G. and N.J.K. designed research; A.B.L.T., C.T., D.J.G., and Y.K. in rodent hippocampal and cortical circuits (2–4, 31), and the phase performed research; A.B.L.T., M.A.K., C.T., D.J.G., Y.K., A.M.G., and N.J.K. analyzed data; of theta rhythms recorded in the human neocortex can modulate and A.B.L.T., M.A.K., A.M.G., and N.J.K. wrote the paper. wide-band (60–200 Hz) high-frequency oscillations (10). Such The authors declare no conflict of interest. theta–gamma nesting is thought to play a role in sequential memory 1To whom correspondence may be addressed. E-mail: [email protected] or [email protected]. organization and maintenance of working memory, and more 2A.M.G. and N.J.K. contributed equally to this work. generally in ‘‘phase coding’’ (25, 31). Based on evidence suggesting This article contains supporting information online at www.pnas.org/cgi/content/full/ that theta rhythms in hippocampal and striatal memory circuits are 0810524105/DCSupplemental. coordinated in rats during learning and performance of a condi- © 2008 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0810524105 PNAS ͉ December 23, 2008 ͉ vol. 105 ͉ no. 51 ͉ 20517–20522 Downloaded by guest on September 26, 2021 Theta Low Gamma High Gamma HFO A B (7-12 Hz) (30-55 Hz) (80-120 Hz) (120-180 Hz) x 10-3 x 10-3 x 10-3 0.3 16 3.2 1.7 Warning Tone Goal Fig. 1. Dynamic amplitude modulation of fast /Hz) /Hz) /Hz) 15 /Hz) Cue Gate Onset 2 2 2 2 2.8 1.6 LFP rhythms by theta phase in the striatum dur- Turn 0.2 14 ing maze runs. (A) T-maze with task events and End 13 Start Turn 0.1 2.4 1.5 run trajectories from a representative session Begin 12 Goal Power (mV Power (mV Power (mV 0 11 Power (mV 2 1.4 with 39 trials. Red markers show photobeam S S S G G G S G W W W To To To W To PT PT PT TB TE TB TE TB TE Ga Ga Ga PT TB TE Ga positions. (B) Average power of striatal oscilla- tions for successive event windows (1 s) over 4 Pre Trial Warning Gate Tone Turn Turn End Goal frequency ranges of interest. Error bars repre- C Cue Opening Start Onset Begin 1 1 1 1 1 1 1 1 sent SEM. Event labels: PT, pre-trial; W, warning /Hz) 2 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 cue; Ga, gate opening; S, start; To, tone onset; 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 TB, turn begin; TE, turn end; G, goal reaching. (C) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Mean power spectra (solid lines) showing char- 0 0 0 0 0 0 0 0 Power (mV 0 5 10 15 0 5 10 15 0 5 10 15 051015 0 5 10 15 051015 051015 051015 acteristic changes in the power peak during Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) perievent windows. Dashed lines represent ϮSD. (D) Phase-to-amplitude comodulograms plotted Warning Gate Tone Turn Pre Trial Start Turn End Goal for each task-event window. Pseudocolor scale D Cue Opening Onset Begin 160 3.5 ) represents modulation index values shown at 3- 140 3i o n 0 right. Positive values indicate a statistically sig- I n d e x ( x 1 120 2.5 t M o d2 u l a nificant (P Ͻ 0.01) phase-to-amplitude cross- 100 1.5 80 1 frequency coupling (see SI Text). Results illus- Amplitude 60 0.5 Frequency (Hz) trated in B–D were obtained from a striatal 40 0 3 5 7 9 3 5 7 9 3 5 7 9 3 5 7 9 3 5 7 9 3 5 7 9 3 5 7 9 3 5 7 9 tetrode in a representative rat by analyzing all Phase Frequency (Hz) trials in the session shown in A.