A ketogenic diet reduces long - term potentiation in the dentate gyrus of freely - 3 behaving rats

31 Ketogenic diets are very low in carbohydrates and can reduce epileptic seizures significantly. 32 This dietary therapy is particularly effective in pediatric and drug-resistant epilepsy. 33 Hypothesized anticonvulsant mechanisms of ketogenic diets focus on increased inhibition and/or 34 decreased excitability/excitation. Either of these consequences might not only reduce seizures 35 but could also affect normal brain function and synaptic plasticity. Here we characterized effects 36 of a ketogenic diet on hippocampal long-term potentiation, a widely studied form of synaptic 37 plasticity. Adult male rats were placed on a control or ketogenic diet for three weeks prior to 38 recording. To maintain the most physiological conditions possible we assessed synaptic 39 transmission and plasticity using chronic in vivo recordings in freely behaving animals. Rats 40 underwent stereotaxic surgery to chronically-implant a recording electrode in the hippocampal 41 dentate gyrus and a stimulating electrode in the perforant path; they recovered for one week. 42 After habituation and stable baseline recording, 5 Hz theta-burst stimulation was delivered to 43 induce long-term potentiation. All animals showed successful plasticity, demonstrating that 44 potentiation was not blocked by the ketogenic diet. Compared to rats fed a control diet, rats fed a 45 ketogenic diet demonstrated significantly diminished long-term potentiation. This decreased 46 potentiation lasted for at least 48h. Reduced potentiation in ketogenic diet-fed rats is consistent 47 with a general increase in neuronal inhibition (or decrease in excitability) and decreased seizure 48 susceptibility. A better understanding of the effects of ketogenic diets on synaptic plasticity and 49 learning is important, as diet-based therapy is often prescribed to children with epilepsy. 50 51