Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Entorhinal–Hippocampal Ensemble Activity during Associative Learning


Nature  510, 143–147 (05 June 2014)

Coordination of entorhinal–hippocampal ensemble activity during associative learning

Kei M. Igarashi,

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, MTFS, 7491 Trondheim, Norway

Center for Learning and Memory, The University of Texas at Austin, Austin, Texas 78712-0805, USA


Accumulating evidence points to cortical oscillations as a mechanism for mediating interactions among functionally specialized neurons in distributed brain circuits. A brain function that may use such interactions is declarative memory—that is, memory that can be consciously recalled, such as episodes and facts. Declarative memory is enabled by circuits in the entorhinal cortex that interface the hippocampus with the neocortex. During encoding and retrieval of declarative memories, entorhinal and hippocampal circuits are thought to interact via theta and gamma oscillations, which in awake rodents predominate frequency spectra in both regions. In favour of this idea, theta–gamma coupling has been observed between entorhinal cortex and hippocampus under steady-state conditions in well-trained rats; however, the relationship between interregional coupling and memory formation remains poorly understood. Here we show, by multisite recording at successive stages of associative learning, that the coherence of firing patterns in directly connected entorhinal–hippocampus circuits evolves as rats learn to use an odour cue to guide navigational behaviour, and that such coherence is invariably linked to the development of ensemble representations for unique trial outcomes in each area. Entorhinal–hippocampal coupling was observed specifically in the 20–40-hertz frequency band and specifically between the distal part of hippocampal area CA1 and the lateral part of entorhinal cortex, the subfields that receive the predominant olfactory input to the hippocampal region. Collectively, the results identify 20–40-hertz oscillations as a mechanism for synchronizing evolving representations in dispersed neural circuits during encoding and retrieval of olfactory–spatial associative memory.

Neural activity was recorded from entorhinal cortex (EC) and CA1 of 17 rats trained to solve a simplified version of an odour–place association task thought to depend on interfacing of the hippocampus with inputs from the olfactory bulb and the piriform cortex via the EC.

We first examined spectral activity in CA1 of five well-trained animals. After these animals had reached the 85% performance criterion, electrodes were implanted across the transverse axis of CA1. Analyses focused on activity during the cue-sampling period, when recall of odour–place associations was expected to be initiated. Cue sampling was associated with strong oscillatory activity in the local field potential (LFP) of CA1. The activity change was strongest in the 20–40-Hz frequency range,   below the gamma-band frequencies that dominate running behaviour and in agreement with previous observations in olfaction-based discrimination tasks. Some increase was observed at ~15–20Hz, but a 20-Hz cut-off was used to avoid confounds with theta harmonics (~14–18Hz). The power of the 20–40-Hz oscillation increased gradually during the cue sampling interval, peaked during the second half, and dropped back as soon as the animal left the port. The magnitude of this oscillation increased from proximal to distal CA1 (dCA1) consistent with the idea that beta-frequency olfactory inputs mediated by the lateral part of the EC (LEC) preferentially reach dCA1.

The observation of 20–40-Hz oscillations in the hippocampus is consistent with reports of such activity during odour discrimination and free running in novel or familiar environments. However, the interaction of these rhythms with external cortical networks and the function of such interactions in memory have remained elusive. Using a hippocampus-dependent associative discrimination task, we have shown that learning is accompanied by coupling of 20–40-Hz oscillations in connected cell populations of LEC and dCA1, and that, in each of these areas, such coupling coincides with the formation of unique odour representations. Error trials and change of odour contingencies were invariably accompanied by reduced coupling and reduced ensemble selectivity, suggesting that the changes are necessary for successful retrieval or retrieval-based navigation. The results identify 20–40-Hz coupling as a potential mechanism for the evolution of functional circuits during encoding of associative memory in entorhinal–hippocampal systems. Coherent firing between LEC and CA1, timed by 20–40-Hz oscillations, may be a prerequisite for the formation of distinct representations for differentially associated odour cues, both because coupling provides sufficient coincidence of pre- and postsynaptic activity for synaptic strengthening to take place and because coincident firing among afferent neurons facilitates such strengthening. Interregional coupling may facilitate the pattern-completion processes required for successful reactivation of newly formed entorhinal and hippocampal cell ensembles.

20–40-Hz oscillations occur widely across the cortex. During olfactory learning, 20–40-Hz oscillations may coordinate activity across distributed areas spanning from the olfactory bulb to the LEC and the hippocampus. Increases in 20–40-Hz rhythms in the olfactory bulb and olfactory cortex have been observed after olfactory learning, in parallel with 20–40-Hz field oscillations in the hippocampus. Widespread 20–40-Hz oscillations have also been observed to emerge at late stages of habit learning in the ventromedial striatum. Because 20–40-Hz oscillations can maintain synchrony with larger conduction delays than faster gamma oscillations, they are particularly suitable for linking activity across widely distributed brain regions such as those participating in olfaction-based memory formation. The strong coincidence of entorhinal–hippocampal 20–40-Hz coupling and the emergence of olfactory neural representations in LEC and dCA1, in parallel with behavioural learning, points to 20–40-Hz oscillations as a key ingredient of the mechanism for induction and expression of long-term memory in distributed cortical circuits.

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