Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model

Abstract

Mesial temporal lobe epilepsy is characterized by focal, recurrent spontaneous seizures, sclerosis and granule cell dispersion (GCD) in the hippocampal formation. Changes in theta rhythm properties have been correlated with the severity of hippocampal restructuring and were suggested as a cause of memory deficits accompanying epilepsy. For severe sclerosis, it has even been questioned whether theta band oscillations persist. We asked how theta oscillations change with graded restructuring along the longitudinal hippocampal axis and whether these changes correlate with the overall severity of temporal lobe epilepsy. We recorded local field potentials in the medial entorhinal cortex and along the septo-temporal axis of the dentate gyrus at sites with different degrees of GCD in freely behaving epileptic mice. Theta frequency was decreased at all recording positions throughout the dentate gyrus and in the medial entorhinal cortex, irrespective of the extent of GCD or the rate of severe epileptic events. The frequency reduction by up to 1.7 Hz, corresponding to 1/3 octaves within the theta range, was present during rest, exploration and running. Despite the frequency reduction, theta oscillations remained coherent across the hippocampal formation and were modulated by running speed as in controls. The reduction in theta frequency thus is likely not a consequence of the local restructuring but rather a global phenomenon affecting the hippocampal formation as a whole.

Expression of brain‐derived neurotrophic factor and structural plasticity in the dentate gyrus and CA2 region correlate with epileptiform activity

“…The first hour of recordings was discarded (to avoid the exploration phase in the recording cage), artifacts were removed manually, discharges were automatically detected, based on a combination of frequency composition and amplitude threshold as described previously, 26,27 and results were visually verified. For analysis of recurrent EA (and baseline activity in controls), mice were preselected (see Methods S1; final numbers: n KA = 6 mice, n NaCl = 4 mice).…”

“…Severe epileptiform events were classified according to the number of discharges, median interdischarge interval, and coefficient of variation using hierarchical clustering, as described previously. 27 A A1…”

Update on temporal lobe‐dependent information processing, in health and disease

“…This theta power decrease has been described to be due, at least in part, to IA. Studies in TLE animal models confirmed the decrease in theta power (Arabadzisz, Antal, Parpan, Emri, & Fritschy, ; Chauvière et al, ) and frequency (Chauvière et al, ; Kilias et al, ) and suggest potential explanations. An impairment of the theta generators, either by modification of the theta pacemaker structure or by aberrant connections (e.g., sprouting) between theta oscillators (Christenson, Leintz, Xamonthiene, Huang, & Krook‐Magnuson, ; Dudek & Shao, ) was proposed, as well as a modification in the resonance features of neurons involved (Marcelin et al, ; Wolfart & Laker, ); for review see (Sharma et al, ).…”

Levetiracetam induction of theta frequency oscillations in rodent hippocampus in vitro

“…Hippocampal theta rhythm (4-12 Hz) plays a key role in cognitive processes in both humans and animals [1,2] and is associated with a variety of cognitively related behaviors, including spatial coding, memory and sniffing exploratory locomotion [3]. The decreased theta activity is correlated with cognitive deficit seen in neurodegenerative disease such as epilepsy and Alzheimer's disease (AD) [4,5,6,7].…”