Correlations between granule cell physiology and bioenergetics in human temporal lobe epilepsy

Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormalities including decreased phosphocreatine (PCr) normalized to ATP. The physiological consequences of these metabolic alterations have not been established. We hypothesized that impaired bioenergetics would correlate with alterations in physiological functions under conditions that strongly activate neural metabolism. We correlated several physiological variables obtained from epileptic human dentate granule cells studied in slices with hippocampal PCr/ATP measured using in vivo magnetic resonance spectroscopy. The physiological variables included: the ability to fire multiple action potentials in response to single stimuli, the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s stimulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/ATP being associated with prolonged recovery times. These data suggest that the bioenergetic impairment seen in this tissue is associated with specific changes in excitatory and inhibitory neuronal responses to synchronized synaptic inputs.