Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy
Abstract
In temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans (females and males) and mice (C57Bl6 males, systemic low-dose kainate model). Using a recently developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the dentate gyrus to perform certain forms of pattern separation. This is because of a subset of granule cells with abnormal bursting that can develop independently of early EEG abnormalities. Overall, our results linking physiology, computation, and cognition in the same mice advance our understanding of episodic memory mechanisms and their dysfunction in epilepsy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 07, 2021
- Source ID
- 10.1523/jneurosci.2439-20.2021
Entities
People
- Antoine Madar
- Bruce P Hermann
- Eli P. Wallace
- Erin I. Plumley
- Jesse A Pfammatter
- Jessica Bordenave
- Mathew V Jones
- Michael Cowie
- Rama Maganti
- Swetha Ravi
Organizations
- Institute for Clinical and Translational Research, University of Wisconsin, Madison
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense