Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies.

Abstract

INTRODUCTION: Learning induces a dynamic reorganization of brain circuits but the neuronal mechanisms underlying this process are not well understood. Interregional gamma-frequency oscillations (~30 to 130 Hz) have been postulated as a mechanism to precisely coordinate upstream and downstream neuronal ensembles, for example, in the hippocampal system. The lateral (LEC) and medial (MEC) entorhinal cortex receive inputs from two distinct streams of cortical hierarchy (the “what” and the “where” paths) and convey these neuronal messages to the hippocampus. However, the mechanisms by which such messages are packaged and integrated or segregated by hippocampal circuits had yet to be explored.

RATIONALE: Neuronal assemblies firing within gamma time frames in an upstream region can most effectively discharge their downstream partners. This gamma-time-scale organization appears essential for physiological functions because manipulations that impair precision timing of spikes in the hippocampus often affect behavior. However, direct support for distinct gamma-frequency communication in appropriate behavioral situations is missing. To bring physiological operations closer to behavior, we designed “spatial” and “object” learning tasks and examined the selective engagement of gamma-frequency communication between the MEC and LEC inputs and their target neuronal assemblies in the hippocampal dentate gyrus. We combined these correlational observations with optogenetic perturbation of gamma oscillations in LEC and MEC, respectively, to test their roles in pathway-specific neuronal communication and learning.

RESULTS: During spatial learning, fast gamma (100 to 150 Hz) oscillations synchronized MEC and dentate gyrus and entrained predominantly granule cells. During object learning, slow gamma (30 to 50 Hz) oscillations synchronized LEC and dentate gyrus and preferentially recruited mossy cells and CA3 pyramidal neurons, suggesting task-specific routing of MEC and LEC messages in the form of gamma-cycle-spike packets of selected cell types. The low- and high-frequency gamma sub-bands were dominant in the outer and middle third of the dentate molecular layer, respectively, and their amplitude maxima were locked to different phases of theta oscillation.

Gamma frequency optogenenetic perturbation of MEC and LEC led to learning impairments in a spatial and object learning task, respectively. In the same animals, the dentate layer–specific low- and high-frequency gamma sub-bands and spike-gamma LFP coupling were selectively reduced, coupled with deterioration of spatial and object-related parameters of dentate neurons.

CONCLUSION: These findings demonstrate that distinct gamma-frequency-specific communication between MEC and LEC and the hippocampal cell assemblies are critical for routing task-relevant information, and our selective gamma-band perturbation experiments suggest that they support specific aspects of learning. We hypothesize that sending neuronal messages by segregated gamma-frequency carriers allows a target “reader” area to disambiguate convergent inputs. In general, these results demonstrate that specific projected gamma patterns dynamically engage functionally related cell assemblies across brain regions in a task-specific manner.