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.
Highlights
In epilepsy, transient fast oscillations in local field potentials called pathological high-frequency oscillations are observed in brain regions near the seizure focus and are hypothesized to play a role in epileptogenesis (Bragin et al, 2004; Staba et al, 2002)
We first determined whether the hippocampus of animals with chronic epilepsy is capable of engaging in two types of high-frequency oscillations, pathological and more normal, ripple-like events
Given that brain states differ between foraging and rest and that normal ripple oscillations are dependent on select brain states, we reasoned that recording across immobile and mobile behavioral states would be useful for assessing the pathology of high-frequency oscillations in epilepsy
Summary
Transient fast oscillations in local field potentials called pathological high-frequency oscillations (pHFOs) are observed in brain regions near the seizure focus and are hypothesized to play a role in epileptogenesis (Bragin et al, 2004; Staba et al, 2002). It is difficult to know whether ripples observed in humans with epilepsy are normal or altered because there are no control data from healthy brains available and because of the difficulty in humans to simultaneously record the activity of many single neurons within a collective brain network We address these questions in an animal model of chronic temporal lobe epilepsy, in which we can record high-frequency oscillations and the neuron ensembles that participate in them from both epileptic and control rats. As a result of each neuron being theta-rhythmically active within spatially restricted fields, principal neurons are sequentially activated within theta cycles when animals transverse a space These emerging theta sequences are compressed and replayed during ripples, which is thought to be important for consolidation of memory during sleep as well as for decision-making and path planning during behavior (Girardeau et al, 2009; Jadhav et al, 2012; Olafsdottir et al, 2015; Pfeiffer and Foster, 2013). We compare the brain state dependencies, cellular participation, and functional role of pHFO and ripple-like oscillations with control ripple oscillations
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