ABSTRACT
Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval.
Subject(s)
Hippocampus , Neurons , Hippocampus/physiology , Neurons/metabolism , Entorhinal Cortex/physiology , Theta Rhythm/physiology , Parvalbumins/metabolism , Action Potentials/physiology , CA1 Region, Hippocampal/physiologyABSTRACT
Episodic learning and memory retrieval are dependent on hippocampal theta oscillation, thought to rely on the GABAergic network of the medial septum (MS). To test how this network achieves theta synchrony, we recorded MS neurons and hippocampal local field potential simultaneously in anesthetized and awake mice and rats. We show that MS pacemakers synchronize their individual rhythmicity frequencies, akin to coupled pendulum clocks as observed by Huygens. We optogenetically identified them as parvalbumin-expressing GABAergic neurons, while MS glutamatergic neurons provide tonic excitation sufficient to induce theta. In accordance, waxing and waning tonic excitation is sufficient to toggle between theta and non-theta states in a network model of single-compartment inhibitory pacemaker neurons. These results provide experimental and theoretical support to a frequency-synchronization mechanism for pacing hippocampal theta, which may serve as an inspirational prototype for synchronization processes in the central nervous system from Nematoda to Arthropoda to Chordate and Vertebrate phyla.
