Homeostatic hippocampal activity against reduced glutamatergic neurotransmission

Glutam ate mediates the majority of excitatory neurotransmission in the brain. Thus, blockade of non-NMDA-type receptors, the main type of ionotropic glutamate receptors under baseline conditions is expected to eliminate neuronal network activity. In the present work, we challenge this simple notion by showing the stability of spontaneous neuronal activity in cultured hippocampal networks in situ. We monitored spiking activity of hippocampal CA3 neuron populations by using a functional Multineuron Calcium Imaging (fMCI) technique. Bath application of competitive non-NMDA receptor antagonists decreased excitatory neurotransmission by approximately 80%. Surprisingly, however, it did not change the level of spontaneous network activity. The antagonists also reduced inhibitory synaptic inputs in CA3 pyramidal cells and thereby maintained the ratio between excitation and inhibition as a whole. Moreover, the antagonists induced an increase in the input resistance of CA3 pyramidal cells. These compensatoiy adaptations in excitability balance and neuronal intrinsic properties may provide ongoing network activity with homeostatic robustness against an external perturbation of non-NMDA receptors. Interestingly, the non-NMDA receptor antagonists reduced epilepsy-like synchronous hyperactivity to the normal activity level.