Are different rhythms good for different functions?

Abstract

This essay discusses the relationship between the physiology of rhythms and potential functional roles. We focus on how the biophysics underlying different rhythms can give rise to different abilities of a network to form and manipulate cell assemblies. We also discuss how changes in the modulatory setting of the rhythms can change the flow of information through cortical circuits, again tying physiology to computation. We suggest that diverse rhythms, or variations of a rhythm, can support different components of a cognitive act, with multiple rhythms potentially playing multiple roles.

Keywords: beta; brain rhythms; gamma; oscillations.

Figure 1

Population gamma activity and competition among excitatory cells. Upper left: A cartoon representation of two interacting cell populations that generate a persistent gamma rhythm; circles labeled “E” represent pyramidal cells and “I” represent FS cells. The two cell populations are reciprocally connected with excitatory (green) and inhibitory (red) synapses from each cell to all other cells. Upper right: Cartoon example of the spiking activity of the two cell populations during persistent gamma activity. Each tick mark represents an action potential (or spike) of an E (green) or I (red) cell. In each cycle of the persistent gamma rhythm, a single pyramidal cell spikes and delivers excitation to the FS cells. The FS cells then spike and inhibit the pyramidal cells. When the inhibition decays sufficiently, one of the pyramidal cells generates another spike, and the rhythm continues. Lower: Increased depolarizing input to a subset of pyramidal cells (yellow box on the left) increases their spiking activity. The population gamma rhythm continues with the “driven” pyramidal cells (yellow box on the right) dominating the excitatory activity.

Figure 2

Different rhythms allow period concatenation. (A) Cross-correlogram showing stable phase relationship between layer 2/3 and layer 5 field potentials in association cortex (S2). When excitation is high, layer 2/3 generates a gamma rhythm (c. 40 Hz) and layer 5 a beta2 rhythm (c. 25 Hz). Reducing excitation then concatenates these two rhythms to generate a beta1 (c. 15 Hz) frequency oscillation in both layers. (B) The asymmetric phase relationship seen for field potentials in (A) is also seen when comparing the timing of layer 2 units with layer 5 units. (C) Intracellular recordings, relative to an on-going beta1 frequency field potential, show the sequence of outputs from different neurons. Each beta1 period begins with a brief burst from layer 5 intrinsically bursting (IB) neurons. This triggers single spikes in superficial fast spiking interneurons (FS). Superficial regular spiking pyramids (RS) spike on the rebound of the resulting IPSP, triggering superficial low-threshold spiking interneurons (LTS) to fire. (D) A cartoon representation of the important cell types in the beta1 rhythm. To the PING model in Figure 1, we add a population of low-threshold spiking (LTS) interneurons and intrinsically bursting (IB) pyramidal cells. We note that the LTS cells inhibit the IB cells, and that the IB cells form excitatory synapses onto all inhibitory cells. A cartoon rastergram is on the right. The beta1 rhythm results from a process of period concatenation. Briefly, the beta1 rhythm propagates through the different cell types as follows. First, the IB cells spike (1) and cause the basket cells to spike (2). The basket cells inhibit the superficial pyramidal cells (3), which recover and spike after one gamma cycle. The superficial pyramidal cell spikes cause the basket and LTS cells to spike (4) which inhibit the IB cells. The IB cells then recover and spike after one beta2 cycle (interval indicated with beta2 label at bottom of this panel) and the rhythm repeats. (A–C) Adapted from Roopun et al. (2008).

Figure 3

Gamma assemblies prefer different theta phases depending on local synapses. (A) Theta phase of gamma spikes, for a single module. Top, a module in the excitation-dominated (ED) regime; red crosses mark the pyramidal cell spikes. The black diamonds mark the O-LM spikes at zero theta phase in all panels. Bottom, a single module in inhibition dominated (ID) regime; light blue crosses mark the pyramidal cell spikes. Theta phases of gamma spikes cluster more in ED regimes. (B) Two coupled modules, in identical ED regimes, receiving different gamma drives. The spike phases on top are for the pyramidal cell of the module that receives stronger gamma drive. The two cell assemblies do not synchronize (Tort et al., 2007). (C) Two coupled modules, receiving identical gamma drive, in different excitation regimes. The red crosses mark activity of the module in ED regime, the light blue marks report activity of the module in ID regime. The theta phases of the gamma spikes in the ID regime do not cluster, so the two gamma signals in the two different modules have the same frequency but have different theta phases.

Figure 4

(A) Increased depolarization of a subset of superficial pyramidal cells (yellow box on the left) produces a gamma rhythm nested in the beta1 activity. The depolarized pyramidal cells, which are connected by all-to-all excitatory synapses, receive enough excitation to generate two bouts of spikes: once after recovering from basket cell input (matching Figure 1) and a second time before receiving basket cell input (yellow shaded regions on the right). (B) Different levels of excitation to subsets of superficial pyramidal cells still produces gamma activity nested in beta1. A population of superficial pyramidal cells, with all-to-all excitatory synapses, receives two levels of increased input, one stronger (yellow) and the other weaker (blue). Both subsets of cells merge to create a gamma rhythm nested in beta1. The subset receiving larger input (shaded yellow on the right) tends to spike more, while the subset receiving weaker input (shaded blue) continues to spike, unlike in PING.

Figure 5

Different rhythms may allow routing of cortical information flow. (A) Medial entorhinal cortex (mEC) generates two different frequencies of gamma rhythm depending on the degree of NMDA receptor-mediated excitation present. In control conditions a c. 40 Hz gamma rhythm is mediated by activity in layer 2 basket cells. In the absence of NMDA receptor-mediated excitation these interneurons become relatively hyperpolarized. The reduction in this source of phasic inhibition allows a second type of interneuron (layer 3 goblet cells) to become active, mediating a lower frequency (c. 30 Hz) gamma rhythm. Examples of reconstructed interneurons of both types and 1 s epochs of intracellularly recorded activity during local gamma rhythm generation are shown. (B) The two gamma rhythms in mEC have modal peak frequencies which correspond to the main resonant frequency of either the hippocampal CA1 or CA3 subnetworks during gamma generation. Spectra show that, in control conditions (NMDA present), mEC frequency matches that of area CA1. In the absence of NMDA drive mEC frequency matches that of area CA3. Below are cartoons illustrating the possible consequences for information flow into hippocampus. Figure from Middleton et al. (2008).

Figure 6

Different rhythms allow for directionality in functional connectivity. (A) Cross-correlogram showing a highly stable phase relationship between association cortex (S2) and primary auditory cortex (A1) when both generate beta2 frequency (c. 25 Hz) oscillations driven by kainate in the presence of cholinergic neuromodulation. (B) While the beta2 frequency rhythms in each area are spectrally the same, the mechanisms underlying them at the local network level are not. S2 beta2 rhythms are almost completely resistant to blockade of fast glutamatergic (SYM = SYM2206, 20 μM) or GABAergic (gabazine, 500 nM) synaptic transmission, whereas the same frequency generated by A1 requires both these components of synaptic transmission. The resulting combination of a rhythm dependent on chemical synaptic activity and one resistant to it results in highly significant partial directed coherence estimates (Granger scores) within the beta2 frequency band: The relatively synaptically inert S2 beta2 rhythm is able to dominate over the synaptically labile A1 beta2 rhythm. Note that in both regions, the accompanying superficial layer gamma rhythm is abolished by synaptic blockade and that, for the gamma rhythm, interactions are bi-directional. Figure from Roopun et al. (2010).