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.

The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

“…The balance between excitation and inhibition may be more critical to neural function and behaviour than either neural excitability or inhibition alone (Bonansco & Fuenzalida, 2016;Cash, Udupa, et al, 2017d;Meunier, Chameau, & Fossier, 2017;Turrigiano, 2011), and evidence suggests TBS may have an influence in this regulatory property in animal (Moreau, Amar, Callebert, & Fossier, 2013) and humans (Chung, Rogasch, Hoy, Sullivan, et al, 2018b;Hoy et al, 2016;Legon et al, 2016). Therefore, exploratory analyses were performed regarding the relationship between iTBS-induced change in P60 and N100 amplitudes in order to examine whether significant differences in any of the iTBS conditions could reflect altered inhibitory/excitatory balances (Noda, Zomorrodi, Cash, et al, 2017d).…”

Bestrophin1‐mediated tonic GABA release from reactive astrocytes prevents the development of seizure‐prone network in kainate‐injected hippocampi

“…Epilepsy is a disorder characterized by recurrent spontaneous seizures due to excessive network activity. Among the multiple mechanisms that are proposed to induce seizures, the most accepted mechanism proposes that seizures are caused by the disruption of synaptic E/I balance, which promotes neuronal hyperexcitability and hypersynchronization, through either an increase in excitatory synaptic transmission or decrease in inhibitory synaptic transmission or both (Bonansco & Fuenzalida, ; Fritschy, ). In particular, it has been suggested that dysfunction of GABAergic signaling is critical for epileptogenesis (Cossart et al, ; Kobayashi & Buckmaster, ; Leroy, Poisbeau, Keller, & Nehlig, ).…”

“…transmission or decrease in inhibitory synaptic transmission or both (Bonansco & Fuenzalida, 2016;Fritschy, 2008). In particular, it has been suggested that dysfunction of GABAergic signaling is critical for epileptogenesis (Cossart et al, 2001;Kobayashi & Buckmaster, 2003;Leroy, Poisbeau, Keller, & Nehlig, 2004).…”

Presynaptic LRP4 Promotes Synapse Number and Function of Excitatory CNS Neurons

“…Indeed, circuit models for diverse neuronal ensembles fail to recapitulate functional patterns unless these aspects are accounted for 1,2 . The misregulation of any one of these organizational parameters can result in neurodevelopmental disorders and intellectual disabilities like autism 3 , epilepsy 4 , and other synaptopathies 5 . Revealing the molecular mechanisms that ensure all of these facets are achieved is a critical step in understanding circuit assembly and function.…”