Potentiation of NMDA Receptors by Withania somnifera on Hippocampal CA1 Pyramidal Neurons

In Ayurveda, Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS (mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/mu l) induced remarkable membrane depolarization (9.75 +/- 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 mu M tetrodotoxin (TTX, 10.17 +/- 0.04 mV, n = 6). In voltage clamp mode (holding potential = -60 mV), mWS induced a dose-dependent non-desensitizing inward current that persisted in the presence of TTX (0.5 mu M), suggesting that the response induced by mWS was purely a postsynaptic event. Interestingly, these inward currents were partially blocked by strychnine, a glycine receptor blocker. Further, mWS potentiated the NMDA response in hippocampal CA1 neurons at low concentrations. Overall, these results suggest that there are compounds in WS with possible glycine mimetic activities, which may be potential targets for inducing memory consolidation in hippocampal CA1 neurons.