The Theta-Gamma Neural Code

Synchronized Activity between the Ventral Hippocampus and the Medial Prefrontal Cortex during Anxiety

Event Abstract Back to Event The frequency of hippocampal theta oscillations and unit firing can be manipulated by changing the t Eva Pastalkova1* and Györgi Buzsaki2 1 HHMI, Janelia Farm Research Campus, United States 2 Rutgers University, CMBN, United States In order to study how theta oscillations organize the temporal patterns of neurons within the hippocampal-entorhinal system, we developed a method which allows us to manipulate the frequency of theta oscillations for short periods of time. We increased or decreased the local temperature within the medial septum using an insulated golden wire, which was connected to a Peltier device above a skull of an animal. We show that local cooling of the medial septum was followed by the decrease of the theta frequency and local heating by the increase of the theta frequency in both, hippocampus and entorhinal cortex. Correspondingly, firing of interneurons as well as pyramidal neurons and their interaction was faster during MS heating and slower during MS cooling. The change of the theta and unit firing frequency did not depend on whether an animal was running on a running wheel or in a maze suggesting that the firing of neurons is controlled by the theta oscillation rather than by the external sensory cues. Thus, heating and cooling of the medial septum can be used to manipulate the frequency of the theta oscillations in the hippocampus and entorhinal cortex, facilitating the study of the relationship between LFP oscillations, neuronal firing and sensory stimuli. Conference: Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25 Feb - 2 Mar, 2010. Presentation Type: Poster Presentation Topic: Poster session I Citation: Pastalkova E and Buzsaki G (2010). The frequency of hippocampal theta oscillations and unit firing can be manipulated by changing the t. Front. Neurosci. Conference Abstract: Computational and Systems Neuroscience 2010. doi: 10.3389/conf.fnins.2010.03.00072 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2010; Published Online: 19 Feb 2010. * Correspondence: Eva Pastalkova, HHMI, Janelia Farm Research Campus, Ashburn, United States, pastak@janelia.hhmi.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Eva Pastalkova Györgi Buzsaki Google Eva Pastalkova Györgi Buzsaki Google Scholar Eva Pastalkova Györgi Buzsaki PubMed Eva Pastalkova Györgi Buzsaki Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Cingulate-Hippocampus Coherence and Trajectory Coding in a Sequential Choice Task

Gamma and theta oscillations have been functionally associated with cognitive processes, such as learning and memory. Synaptic conductances play an important role in the generation of intrinsic network rhythmicity, but few studies have examined the effects of voltage-gated ion channels (VGICs) on these rhythms. In this report, we have used a pyramidal-interneuron-gamma (PING) network consisting of excitatory pyramidal cells and two types of inhibitory interneurons. We have constructed a conductance-based neural network incorporating a persistent sodium current (INaP), a delayed rectifier potassium current (IKDR), a inactivating potassium current (IA) and a hyperpolarization-activated current (IH). We have investigated the effects of several conductances on network theta and gamma frequency oscillations. Variation of all conductances of interest changed network rhythmicity. Theta power was altered by all conductances tested. Gamma rhythmogenesis was dependent on IA and IH. The IKDR currents in excitatory pyramidal cells as well as both types of inhibitory interneurons were essential for theta rhythmogenesis and altered gamma rhythm properties. Increasing INaP suppressed both gamma and theta rhythms. Addition of noise did not alter these patterns. Our findings suggest that VGICs strongly affect brain network rhythms. Further investigations in vivo will be of great interest, including potential effects on neural function and cognition.

Theta and gamma oscillations have been linked to episodic memory processes in various studies. Both oscillations seem to be vital for processes guided by the medial temporal lobe, such as the retrieval of information from memory. While theta oscillations increase with successful memory, it is unclear what the unique contribution of theta is to various subcomponents of memory. On the other hand, memory-related gamma oscillations have been mainly reported in the hippocampus, leaving the role of neocortical gamma in memory underexplored. In this study, we investigated how unique variability in memory accuracy and memory confidence contributes to fluctuations in theta and gamma power. To this end, we recorded EEG from 54 participants while they performed a source memory task. From this task we obtained their item memory accuracy, source memory accuracy, item memory confidence, and source memory confidence. These behavioral measures were put in a trial-by-trial linear mixed effects model to uncover their unique contribution to the oscillatory power in frontal and parietal regions. Our results are in line with the involvement of theta oscillations in both memory accuracy and confidence, but seem to indicate a main role for theta oscillations in memory-related confidence. In addition, we found that gamma oscillations play various roles in memory processing, dependent on brain region.

Theta frequency oscillations are a predominant feature of rhythmic activity in the hippocampus. We demonstrate that hippocampal area CA1 generates atropine-resistant theta population oscillations in response to metabotropic glutamate receptor activation under conditions of reduced AMPA receptor activation. This activity occurred in the absence of inputs from area CA3 and extra-ammonic areas. Field theta oscillations were co-expressed with pyramidal distal apical dendritic burst spiking and were temporally related to trains of IPSPs with slow kinetics. Pyramidal somatic responses showed theta oscillations consisted of compound inhibitory synaptic potentials with initial IPSPs with slow kinetics followed by trains of smaller, faster IPSPs. Pharmacological modulation of IPSPs altered the theta oscillation suggesting an inhibitory network origin. Somatic IPSPs, dendritic burst firing and stratum pyramidale interneuron activity were all temporally correlated with spiking in stratum oriens interneurons demonstrating intrinsic theta-frequency oscillations. Disruption of spiking in these interneurons was accompanied by a loss of both field theta and theta frequency IPSP trains. We suggest that population theta oscillations can be generated as a consequence of intrinsic theta frequency spiking activity in a subset of stratum oriens interneurons controlling electrogenesis in pyramidal cell apical dendrites.

Learning related interactions among neuronal systems involved in memory processes

A detailed biophysical model of hippocampal region CA3 was constructed to study how GABAergic modulation influences place field development and the learning and recall of sequence information. Simulations included 1,000 multicompartmental pyramidal cells, each consisting of seven intrinsic and four synaptic currents, and 200 multicompartmental interneurons, consisting of two intrinsic and four synaptic currents. Excitatory rhythmic septal input to the apical dendrites of pyramidal cells and both excitatory and inhibitory input to interneurons at theta frequencies provided a cellular basis for the development of theta and gamma frequency oscillations in population activity. The fundamental frequency of theta oscillations was dictated by the driving rhythm from the septum. Gamma oscillation frequency, however, was determined by both the decay time of the gamma-aminobutyric acid-A (GABA(A))-receptor-mediated synaptic current and the overall level of excitability in interneurons due to alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and N-methyl-D-aspartate (NMDA)-receptor-gated channel activation. During theta population activity, total GABA(B)-receptor-mediated conductance levels were found to gradually rise and fall in rhythmic fashion with the predominant population frequency (theta rhythm). This resulted in periodic GABA(B)-receptor-mediated suppression of excitatory synaptic transmission at recurrent collaterals (intrinsic fibers) of pyramidal cells and suppression of inhibitory synaptic transmission to both pyramidal cells and interneurons. To test the ability of the model to learn and recall temporal sequence information, a completion task was employed. During learning, the network was presented a sequence of nonorthogonal spatial patterns. Each input pattern represented a spatial "location" of a simulated rat running a specific navigational path. Hebbian-type learning was expressed as an increase in postsynaptic NMDA-receptor-mediated conductances. Because of several factors including the sparse, asymmetric excitatory synaptic connections among pyramidal cells in the model and a sufficient degree of random "background" firing unrelated to the input patterns, repeated simulated runs resulted in the gradual emergence of place fields where a given cell began to respond to a contiguous segment of locations on the path. During recall, the simulated rat was placed at a random location on the previously learned path and tested to see whether the sequence of locations could be completed on the basis of this initial position. Periodic GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic but not afferent fibers resulted in sensory information about location being dominant during early portions of each theta cycle when GABA(B)-receptor-related effects were highest. This suppression declined with levels of GABA(B) receptor activation toward the end of a theta cycle, resulting in an increase in synaptic transmission at intrinsic fibers and the subsequent recall of a segment of the entire location sequence. This scenario typically continued across theta cycles until the full sequence was recalled. When the GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic fibers was not included in the model, place field development was curtailed and the network consequently exhibited poor learning and recall performance. This was, in part, due to increased competition of information from intrinsic and afferent fibers during early portions of each theta cycle. Because afferent sensory information did not dominate early in each cycle, the current location of the rat was obscured by ongoing activity from intrinsic sources. (ABSTRACT TRUNCATED)

Theoretical and experimental studies suggest that oscillatory modes of processing play an important role in neuronal computations. One well supported idea is that the net excitatory input during oscillations will be reported in the phase of firing, a ‘rate-to-phase transform’, and that this transform might enable a temporal code. Here, we investigate the efficiency of this code at the level of fundamental single cell computations. We first develop a general framework for the understanding of the rate-to-phase transform as implemented by single neurons. Using whole cell patch-clamp recordings of rat hippocampal pyramidal neurons in vitro, we investigated the relationship between tonic excitation and phase of firing during simulated theta frequency (5 Hz) and gamma frequency (40 Hz) oscillations, over a range of physiological firing rates. During theta frequency oscillations, the phase of the first spike per cycle was a near-linear function of tonic excitation, advancing through a full 180 deg, from the peak to the trough of the oscillation cycle as excitation increased. In contrast, this relationship was not apparent for gamma oscillations, during which the phase of firing was virtually independent of the level of tonic excitatory input within the range of physiological firing rates. We show that a simple analytical model can substantially capture this behaviour, enabling generalization to other oscillatory states and cell types. The capacity of such a transform to encode information is limited by the temporal precision of neuronal activity. Using the data from our whole cell recordings, we calculated the information about the input available in the rate or phase of firing, and found the phase code to be significantly more efficient. Thus, temporal modes of processing can enable neuronal coding to be inherently more efficient, thereby allowing a reduction in processing time or in the number of neurons required.

The coupling of gamma oscillation (~ 40+ Hz) amplitude to the phase of ongoing theta (~ 6 Hz) oscillations has been proposed to be directly relevant for memory performance. Current theories suggest that memory capacity scales with number of gamma cycles that can be fitted into the preferred phase of a theta cycle. Following this logic, transcranial alternating current stimulation (tACS) may be used to adjust theta cycles (increasing/decreasing theta frequency) to decrease or increase memory performance during stimulation. Here, we used individualized EEG-informed theta tACS to (1) experimentally “slow down” individual theta frequency (ITF), (2) evaluate cognitive after effects on a battery of memory and learning tasks, and (3) link the cognitive performance changes to tACS-induced effects on theta-band oscillations as measured by post EEG. We found frequency- and task-specific tACS after effects demonstrating a specific enhancement in memory capacity. This tACS-induced cognitive enhancement was specific to the visual memory task performed immediately after tACS offset, and specific to the ITF-1 Hz (slowing) stimulation condition and thus following a protocol specifically designed to slow down theta frequency to enhance memory capacity. Follow-up correlation analyses in this group linked the enhanced memory performance to increased left frontal-parietal theta-band connectivity. Interestingly, resting-state theta power immediately after tACS offset revealed a theta power increase not for the ITF-1 Hz group, but only for the ITF group where the tACS frequency was ‘optimal’ for entrainment. These results suggest that while individually calibrated tACS at peak frequency maximally modulates resting-state oscillatory power, tACS stimulation slightly below this optimal peak theta frequency is better suited to enhance memory capacity performance. Importantly, our results further suggest that such cognitive enhancement effects can last beyond the period of stimulation and are linked to increased network connectivity, opening the door towards more clinical and applied relevance of using tACS in cognitive rehabilitation and/or neurocognitive enhancement.

In the presence of muscarinic cholinergic modulation in vitro, persistent spiking neurons of medial entorhinal cortex (mEC) exhibit bistability in that they can be switched from quiescence to spiking by a brief depolarizing input. The spiking state is thought to be maintained by a positive feedback loop between a nonspecific, calcium-sensitive cationic current (ICAN) carried by canonical transient receptor potential (TRPC) channels and heightened intracellular calcium levels sustained during sufficiently fast spiking. Bistable persistent spiking (PSB) has been observed across layers and cell types in mEC and has been implicated in working memory and grid cell function, so cholinergic modulation of TRPC channels represents a potentially fundamental mechanism shaping the spiking output of mEC neurons. However, spiking of mEC neurons during navigation and goal directed behavior in vivo is strongly theta modulated (4-12 Hz), and it is not known how the PSB mechanism may interact with theta oscillations. In the present study we evaluated the effect of muscarinic modulation on input-output processing of mEC neurons to tonic, slowly varying, and oscillatory inputs. First, we investigated the frequency to injected current (FI) relationship using step and ramp current injection protocols in the presence of the muscarinic agonist carbachol (CCh). FI measures made following suprathreshold pre-pulse current injections exhibited higher spike frequencies than when measured following subthreshold pre-pulses, illustrating a spike-history dependence of the FI relationship. The instantaneous spike frequency measured during a range of current steps showed a positive slope for most PSB neurons, indicating that ICAN acts as a reverse spike frequency adaptation mechanism. In response to linearly increasing ramp current stimuli, mEC neurons showed a steep acceleration followed by a plateau of spike frequency. Spike frequency hysteresis during decreasing ramp stimuli demonstrated significant adaptation for higher input levels, but spiking was often maintained at lower levels of injected current. Next, using different combinations of theta frequency sinewave current injections and DC holding currents, we were able to generate a range of spiking patterns where spikes were elicited on different proportions of theta cycles and at different phases of the theta input. With muscarinic activation, spiking was elicited on a higher proportion of theta cycles and at earlier phases of the oscillatory input for lower levels of tonic current input. A subset of recorded neurons exhibitted repeated sequences of intrinsic phase precessing spiking behavior. Similar to the plateau in spike rate observed with ramp stimuli, in response to stimuli composed of sinewaves superimposed on ramps, spiking phase rapidly advanced and maintained an ‘early-phase plateau’ as DC current continued to increase. Taken together, we demonstrate that muscarinic modulation of TRPC channels determines the gain of the frequency to injected current relationship of mEC neurons, interacts with adaptation mechanisms to generate spike history dependencies of spike rate including hysteresis, and shapes the distribution of spiking phases relative to oscillatory input. We propose that increasing activation of ICAN by spike-triggered calcium influx as an animal enters a firing field may provide a cellular mechanism contributing to theta phase precession of mEC grid cells.

Chapter 30 Insights into the functional organization of limbic cortical circuits from studies of evoked potentials and spontaneous activity

Imaging and neural modelling in episodic and working memory processes

During study trials of a recognition memory task, alpha (∼10 Hz) oscillations decrease, and concurrently, theta (4-8 Hz) oscillations increase when later memory is successful versus unsuccessful (subsequent memory effect). Likewise, at test, reduced alpha and increased theta activity are associated with successful memory (retrieval success effect). Here we take an individual-differences approach to test three hypotheses about theta and alpha oscillations in verbal, old/new recognition, measuring the difference in oscillations between hit trials and miss trials. First, we test the hypothesis that theta and alpha oscillations have a moderately mutually exclusive relationship; but no support for this hypothesis was found. Second, we test the hypothesis that theta oscillations explain not only memory effects within participants, but also individual differences. Supporting this prediction, durations of theta (but not alpha) oscillations at study and at test correlated significantly with d' across participants. Third, we test the hypothesis that theta and alpha oscillations reflect familiarity and recollection processes by comparing oscillation measures to ERPs that are implicated in familiarity and recollection. The alpha-oscillation effects correlated with some ERP measures, but inversely, suggesting that the actions of alpha oscillations on memory processes are distinct from the roles of familiarity- and recollection-linked ERP signals. The theta-oscillation measures, despite differentiating hits from misses, did not correlate with any ERP measure; thus, theta oscillations may reflect elaborative processes not tapped by recollection-related ERPs. Our findings are consistent with alpha oscillations reflecting visual inattention, which can modulate memory, and with theta oscillations supporting recognition memory in ways that complement the most commonly studied ERPs.

Drugs and human memory (part 1): Clinical, theoretical, and methodologic issues.