Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats

Abstract

Ketogenic diets are low-carbohydrate, sufficient protein, high-fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely-behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input–output curves) or short-term plasticity (using the paired-pulse ratio), it did reduce the magnitude of long-term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet-feeding on the induction magnitude but not the maintenance of long-term potentiation. The lack of effect of the diet on baseline transmission and the paired-pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure-susceptible network may limit seizure-induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy.

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

“…We also found a lack of effect of KD feeding on working memory in control mouse strains [48] and a lack of effect on baseline hippocampal electrophysiology in vitro in control strains (but an impact on chemically-induced epileptiform activity; [56]). We found normal in vivo baseline hippocampal field potential activity (but a lessening of induced seizures or tetanus-induced potentiation; [53,54,57]. Work from other laboratories is largely in agreement (for instance [76,77]).…”

“…between 3 and 4 weeks of dietary treatment. This length of diet treatment was chosen based on our prior observations that rodents are in significant ketosis at these times on these particular KDs and that KDs have significant behavioral and electrophysiological effects at these times including improvements in autistic-type behaviors in the BTBR model [39,52–57]. Spontaneous overt convulsions begin in EL mice of both sexes at ages that depend somewhat on the type and amount of handling, consistent with the expected developmental progression of the phenotype, but typically older than our testing age [58,59].…”

1. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study

“…In freely behavioural rats, a ketogenic diet-although not significantly altering baseline excitability-did reduce the magnitude of long-term potentiation plastic mechanisms in the hippocampal dentate gyrus [11,25]. Our results seem to be in perfect agreement with those provided by the animal models.…”

“…This avoids any influence on the initial facilitatory mechanism. Reduced potentiation/hyperresponsivity mechanisms in ketogenic diet-fed rats [11,25] is consistent with a general modulation of cortical excitability. This was confirmed by the observation that KD is a useful tool in controlling childhood seizures [27,28].…”

The effect of ketogenic diet on behaviors and synaptic functions of naive mice

“…Many studies even failed to find its influence on cognitive function (Thio et al, ; Fukushima et al, ). Electrophysiologically, several studies demonstrated impaired long‐term potentiation (LTP) by KD in freely behaving rats (Koranda, Ruskin, Masino, & Blaise, ; Blaise, Ruskin, Koranda, & Masino, ), despite of that the other find negative results (Thio et al, ). In addition, KD is shown to increase sociability in young male rats (Kasprowska‐Liskiewicz et al, ).…”