Rhythmic Activity in the Hippocampus and Entorhinal Cortex is Impaired in a Model of Kainate Neurotoxicity in Rats in Free Behavior

Malkov, Anton; Shevkova, Liudmila; Latyshkova, Alexandra; Kitchigina, Valentina F.

doi:10.1007/s11055-020-01041-7

Cited by 3 publications

(4 citation statements)

References 69 publications

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“…LFP records showed that the theta rhythm was dominant in the hippocampus, mEC and mPFC during the tests. Analysis of oscillation parameters in the hippocampus showed that movement of the rats from the periphery to the center of the field was accompanied by a significant increase in the frequency of the theta rhythm (7.46 ± 0.4 Hz for exploration vs. 6.81 ± 0.14 Hz for background, F(1,10) = 6.913, p = 0.0465; see results in Malkov et al, 2021). The slow gamma rhythm showed no significant changes as the rats started exploration.…”

Section: Resultsmentioning

confidence: 86%

“…These processes could underlie the increase in the theta coherence between the hippocampus and mEC during the exploration of objects with temporal order novelty that we observed in the rats in our experiments. Hyperactivation caused by kainate injection may lead to an increase in the level of hippocampal-entorhinal phasic interactions (Froriep et al 2012, Kitchigina, 2018, followed by an increase in the background interstructural coherence (Malkov et al 2021).…”

Section: Specific Changes In the Fast Gamma Rhythm During Object Expl...mentioning

confidence: 99%

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Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: Impairment in epileptogenic rats

Malkov

Shevkova

Latyshkova

et al. 2022

Experimental Neurology

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Section: Resultsmentioning

confidence: 86%

Section: Specific Changes In the Fast Gamma Rhythm During Object Expl...mentioning

confidence: 99%

Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: Impairment in epileptogenic rats

Malkov

Shevkova

Latyshkova

et al. 2022

Experimental Neurology

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“…The spatial coherence of theta oscillations is also greatly decreased near CA3 within the epileptic hippocampus, as well as between regions such as dentate gyrus and entorhinal cortex 70,72–74 . Also disrupted are microscale measures of hippocampal theta coordination, including theta–gamma coupling and neuronal phase coordination with the theta rhythm, and the weakening of theta–gamma coupling is correlated with spatial memory deficits 75,76 …”

Section: Epileptic Septohippocampal Networkmentioning

confidence: 99%

“…70,[72][73][74] Also disrupted are microscale measures of hippocampal theta coordination, including theta-gamma coupling and neuronal phase coordination with the theta rhythm, and the weakening of theta-gamma coupling is correlated with spatial memory deficits. 75,76 Recent studies have investigated how temporal lobe epilepsy impacts hippocampal function at the neuronal level during memory. CA1 interneurons in epileptic rats displayed firing patterns that were significantly less aligned with phase of the theta rhythm relative to nonepileptic rats.…”

Section: Septohippocampal Circuitry and Mechanisms Of Theta Rhythm Ge...mentioning

confidence: 99%

Evidence supporting deep brain stimulation of the medial septum in the treatment of temporal lobe epilepsy

et al. 2022

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Electrical brain stimulation has become an essential treatment option for more than one third of epilepsy patients who are resistant to pharmacological therapy and are not candidates for surgical resection. However, currently approved stimulation paradigms achieve only moderate success, on average providing approximately 75% reduction in seizure frequency and extended periods of seizure freedom in nearly 20% of patients. Outcomes from electrical stimulation may be improved through the identification of novel anatomical targets, particularly those with significant anatomical and functional connectivity to the epileptogenic zone. Multiple studies have investigated the medial septal nucleus (i.e., medial septum) as such a target for the treatment of mesial temporal lobe epilepsy. The medial septum is a small midline nucleus that provides a critical functional role in modulating the hippocampal theta rhythm, a 4–7‐Hz electrophysiological oscillation mechanistically associated with memory and higher order cognition in both rodents and humans. Elevated theta oscillations are thought to represent a seizure‐resistant network activity state, suggesting that electrical neuromodulation of the medial septum and restoration of theta‐rhythmic physiology may not only reduce seizure frequency, but also restore cognitive comorbidities associated with mesial temporal lobe epilepsy. Here, we review the anatomical and physiological function of the septohippocampal network, evidence for seizure‐resistant effects of the theta rhythm, and the results of stimulation experiments across both rodent and human studies, to argue that deep brain stimulation of the medial septum holds potential to provide an effective neuromodulation treatment for mesial temporal lobe epilepsy. We conclude by discussing the considerations necessary for further evaluating this treatment paradigm with a clinical trial.

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Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: impairment in epileptogenic rats

Malkov¹,

Shevkova

Latyshkova³

et al. 2021

Preprint

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Cortical oscillations in different frequency bands have been shown to be intimately involved in exploration of environment and cognition. Here, the local field potentials in the hippocampus, the medial prefrontal cortex (mPFC), and the medial entorhinal cortex (mEC) were recorded simultaneously in rats during the execution of the episodic-like memory task. The power of hippocampal theta (~4-10 Hz), slow gamma (~25-50 Hz), and fast gamma oscillations (~55-100 Hz) was analyzed in all structures examined. Particular attention was paid to the theta coherence between three mentioned structures. The modulation of the power of gamma rhythms by the phase of theta cycle during the execution of the episodic-like memory test by rats was also closely studied. Healthy rats and rats one month after kainate-induced status epilepticus (SE) were examined. Paroxysmal activity in the hippocampus (high amplitude interictal spikes), excessive excitability of animals, and the death of hippocampal and dentate granular cells in rats with kainate-evoked SE were observed, which indicated the development of seizure focus in the hippocampus (epileptogenesis). One month after SE, the rats exhibited a specific impairment of episodic memory for the what-where-when triad: unlike healthy rats, epileptogenic SE animals did not identify the objects during the test. This impairment was associated with the changes in the characteristics of theta and gamma rhythms and specific violation of theta coherence and theta/gamma coupling in these structures in comparison with the healthy animals. We believe that these disturbances in the cortical areas play a role in episodic memory dysfunction in kainate-treated animals. These findings can shed light on the mechanisms of cognitive deficit during epileptogenesis.

show abstract

Rhythmic Activity in the Hippocampus and Entorhinal Cortex is Impaired in a Model of Kainate Neurotoxicity in Rats in Free Behavior

Cited by 3 publications

References 69 publications

Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: Impairment in epileptogenic rats

Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: Impairment in epileptogenic rats

Evidence supporting deep brain stimulation of the medial septum in the treatment of temporal lobe epilepsy

Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: impairment in epileptogenic rats

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