Exogenously applied KYNA suppressed spontaneous glutamatergic activity in the hippocampal samples obtained from patients with MTLE-HS
To investigate the role of exogenously applied KYNA on glutamatergic neurotransmission, the tissue slices of the above-mentioned groups were perfused with 10 µM KYNA for 30 mins. The frequency and amplitude were significantly reduced after 30 mins perfusion of KYNA in comparison to those of basal values in both groups (Table 1). The cumulative distribution of inter-event intervals displaced toward longer interval and that of peak amplitudes displaced towards shorter amplitude (Figure 5b, c and e, f). However, Rise time and τd was not affected (Table 1). The magnitude of percentage reduction of the frequency was significantly enhanced in the hippocampal samples in comparison to the non-seizure controls (16.34± 0.92% in non-seizure control vs 30.72 ± 1.87% in MTLE-HS; Figure 5g). At low micro molecular concentration, KYNA predominantly exerts inhibition through NMDA receptors; but in the present scenario, inhibitory action of KYNA was significantly enhanced in case of MTLE-HS which may be due to upregulation of NMDA receptors. Now, to investigate the contribution of inhibitory action of KYNA mediated through the NMDA receptors, the slices were perfused with 50µM APV alone for 10 mins which blocked only NMDA receptors. APV suppressed the frequency by 42.83 ± 2.26% in the non-seizure controls and 58.17 ± 2.06% in the MTLE-HS group respectively (Figure 5h and i) with a significant difference between the two groups suggesting the role of enhanced tonic NMDA receptor activity in altered synaptic transmission in the hippocampal samples of the MTLE-HS patients. For KYNA, the magnitude of reduction of the frequency was significantly reduced than that of APV (Figure 5j), suggesting that although its primary target are NMDA receptors, but it also has some target sites which are different from it.