Clinically relevant concentrations of ketamine mainly affect long-term potentiation rather than basal excitatory synaptic transmission and do not change paired-pulse facilitation in mouse hippocampal slices

•The effect of ketamine on brain excitatory synapses was studied.•Ketamine affects long-term potentiation in a dose dependent manner.•Paired-pulse facilitation ratio was not affected by ketamine.•Only higher concentrations of ketamine affected basal synaptic transmission.

Ketamine, an analgesic/anesthetic drug, is increasingly popular in clinical practice due to its analgesic properties and importance for emergency procedures. The impact of ketamine on basal excitatory synaptic transmission and synaptic plasticity are not yet fully understood. Therefore we investigated the effects of different concentrations of ketamine on basal excitatory synaptic transmission and on two forms of synaptic plasticity: paired-pulse facilitation (PPF) and long-term potentiation (LTP). Evoked field excitatory postsynaptic potentials (fEPSP) were recorded in Schaffer fiber – CA1 pyramid synapses of mouse hippocampal slices and the initial slope of the fEPSP was measured to estimate the percentage of inhibition of the basal synaptic transmission. Presynaptic volley amplitude, PPF and LTP induction and maintenance were also calculated. For basal synaptic transmission and PPF increasing concentrations of ketamine (1, 3, 10, 30, 100, 200, 300 and 600 μM) were applied to each slice and for LTP individual slices were used for each concentration (3, 10, 30 or 100 μM). Clinically relevant concentrations of ketamine decreased LTP in a concentration-dependent manner without changing PPF, whereas basal excitatory synaptic transmission and presynaptic volley amplitude was affected only with high concentrations of ketamine (300 and 600 μM). These results allow dissociating the blockade of LTP from a reduced synaptic input in the action of clinically relevant concentrations of ketamine in the CA1 region of the mouse hippocampus. Moreover, this work shows that the effects of ketamine on LTP and on basal synaptic transmission are dependent of the concentration used.