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

Hindawi Publishing Corporation Neural Plasticity Volume 2016, Article ID 8607038, 13 pages http://dx.doi.org/10.1155/2016/8607038 Review Article Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain Christian Bonansco1 and Marco Fuenzalida1,2 1 Centro de Neurobiologı́a y Plasticidad Cerebral (CNPC), Instituto de Fisiologı́a, Facultad de Ciencias, Universidad de Valparaı́so, Gran Bretaña Avenida 1111, 2360102 Valparaı́so, Chile 2 Núcleo Milenio en Biologı́a de Enfermedades Neurosiquiátricas, Instituto de Fisiologı́a, Facultad de Ciencias, Universidad de Valparaı́so, Gran Bretaña Avenida 1111, 2360102 Valparaı́so, Chile Correspondence should be addressed to Christian Bonansco; and Marco Fuenzalida; Received 30 October 2015; Revised 20 January 2016; Accepted 31 January 2016 Academic Editor: Long-Jun Wu Copyright © 2016 C. Bonansco and M. Fuenzalida. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 excitatoryinhibitory (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. 1. Introduction Epilepsy is characterized by spontaneous recurrent seizures and comprises a diverse group of syndromes with different aetiologies [1]. Epilepsy is the second most common brain disorder, affecting about 1% of the world’s population [2]. Temporal lobe epilepsy (TLE) remains as one of the most severe and frequent pharmacoresistant types of focal acquired epilepsies. The recurrent seizure is an electrographic hallmark of several types of epilepsy, which consist in an excessive synchronous discharge of cerebral neurons, generated in one or more neuron populations (i.e., epileptic focus) [3]. The electrical activity in epileptic network is associated with an E/I synaptic imbalance, which promotes neuronal hyperexcitability and hypersynchronization, through an increase in excitatory neurotransmission as well as decrease of inhibitory neurotransmission and/or GABA-mediated hyperexcitability [4–6]. During the seizures, associated with heightened neuronal excitability and abnormal synchronization of discharge in the epileptic focus, the disruption of brain functions occurs [7]. Much of the knowledge about neurobiology of epilepsy has been attained from resected temporal lobe tissues from patients, whereas the cellular basis of epilepsy has been obtained from acute experimental models of seizures (i.e., ictogenesis) [8, 9], which contrasts with the limited understanding of neurobiological mechanisms of epilepsy development (epileptogenesis) [10, 11] (see Box 1). Both inhibitory and excitatory synapses are found to exhibit important changes that can mediate the initiation and evolution of self-sustaining seizures. The synaptic plasticity is essential to normal brain function such as our ability to learn and modify our behaviour. Several evidences have showed that astrocytes can modulate the synaptic plasticity and excitability in both excitatory and inhibitory synaptic circuits [12–14]. Currently, experimental evidence suggests that the start, progress, and consolidation of epileptic stage could overlap with the mechanisms underlying the long-term plasticity, learning, and memory [15, 16], which could be explained by an alteration of the factors that regulate the synaptic plasticity of excitatory and inhibitory circuits. Here, we will review the main 2 evidences in those cellular and molecular alterations with focus on the synaptic plasticity that conducts to E/I imbalance and a pronounced vulnerability of the brain to epilepsy. Box 1 Kindling and Long-Term Plasticity in Hippocampal Formation. Epilepsy encloses a set of neurological disorders of diverse aetiology, characterized by the development of gradual and progressive spontaneous seizures, which increase in recurrence and severity with time. To study epilepsy, both acute and chronic models have been developed [17]. Kindling, one of the chronic models of experimental epileptogenesis more extensively used, can be induced either in vivo (i.e., freely moving rats) [8, 18–20] or in vitro (i.e., brain slices) [21–23], allowing reproducing the progressive development of disease. The kindling protocol consists in the repetitive presentation of stimuli (either chemical or electrical) on a nervous structure, usually amygdala or hippocampus, at subconvulsive intensities, which elicits gradual and progressive augmentation of electroencephalographic (EEG) activity after stimuli and behavioural. In several pharmacological and acute models of epileptogenesis, the epileptic state is reached after spontaneous recurrent seizures [24, 25]. EEG activity corresponding to tonic-clonic firing of population spikes, namely, after discharge (AD), can be detected in stimulated structure as well as in projection areas. This AD or electrographic seizure (i.e., EGSs in vitro) has been attributed to ictal discharges as product to the increase of synchronous activity and hyperexcitability of a large group of neurons [26]. The long-term changes in the synaptic efficacy are activitydependent of network and can produce either facilitation or depression, depending on the stimulus parameters and repetition [27]. In hippocampal neurons, long-term potentiation (LTP) of glutamatergic synapses produces the strengthening of synaptic efficacy, which can be induced by high-frequency stimulation or by coincidence between pre- and postsynaptic activity. As well as in excitatory synapses, the neuronal activity can trigger LTP or LTD of GABAergic synaptic strength. The strength of GABAergic inhibition can regulate the ability of excitatory synapses to undergo long-term plasticity, a key mechanism underlying the hippocampal circuit excitability and modifying the learning and memory process. Interestingly, a similar repetitive stimulation protocol used to induce LTP at glutamatergic can also trigger LTD at GABAergic synapses in CA1 pyramidal neurons [28, 29]. Such studies have allowed revealing the progress and consolidation of the epileptic stage as an abnormal form of long-term plasticity [15, 16], which seems to require simultaneous (...truncated)