The impact of pathological high-frequency oscillations on hippocampal network activity in rats with chronic epilepsy

Author:

Ewell Laura A12ORCID,Fischer Kyle B13,Leibold Christian45ORCID,Leutgeb Stefan16ORCID,Leutgeb Jill K1ORCID

Affiliation:

1. Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, La Jolla, United States

2. Institute of Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Bonn, Germany

3. Neuroscience Graduate Program, University of California, San Diego, La Jolla, United States

4. Department Biologie II, Ludwig-Maximilians-Universität München, Martinsried, Germany

5. Berstein Center for Computational Neuroscience Munich, Martinried, Germany

6. Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, United States

Abstract

In epilepsy, brain networks generate pathological high-frequency oscillations (pHFOs) during interictal periods. To understand how pHFOs differ from normal oscillations in overlapping frequency bands and potentially perturb hippocampal processing, we performed high-density single unit and local field potential recordings from hippocampi of behaving rats with and without chronic epilepsy. In epileptic animals, we observed two types of co-occurring fast oscillations, which by comparison to control animals we could classify as ‘ripple-like’ or ‘pHFO’. We compared their spectral characteristics, brain state dependence, and cellular participants. Strikingly, pHFO occurred irrespective of brain state, were associated with interictal spikes, engaged distinct subnetworks of principal neurons compared to ripple-like events, increased the sparsity of network activity, and initiated both general and immediate disruptions in spatial information coding. Taken together, our findings suggest that events that result in pHFOs have an immediate impact on memory processes, corroborating the need for proper classification of pHFOs to facilitate therapeutic interventions that selectively target pathological activity.

Funder

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

Epilepsy Foundation

Hellman Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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