Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

Abstract

Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

Figure 1

Glutamatergic and GABAergic long-term plasticity and tripartite neuronal-astroglial network in normal and epileptic brain. (a) During physiological neuronal activity, coincidence between postsynaptic depolarization and glutamatergic (orange) and GABAergic interneuron (green) simultaneously activated induces increase of synaptic efficacy (i.e., mean amplitude of postsynaptic response) in both glutamatergic [CB1] synapses (LTP) at the same time of a decrease of efficacy of GABAergic transmission (LTD; A). (B) By GABAergic and glutamatergic input integration, the net increase in membrane potential falls below the seizure threshold (ST). (b) During epileptiform neuronal activity, astroglial hyperexcitation through GABA_ARs, GluRs, and/or eCBsRs activation, which increases the intracellular Ca²⁺ release of astroglial glutamate, increasing the excitatory neurotransmission while inhibitory transmission remains unchanged (A). (B) In this condition, glutamatergic/GABAergic rate results in an excitatory imbalance, exceeding the seizure threshold.