The following are the supplementary data related to this

The following are the supplementary data related to this article.
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INTRODUCTION Human hypothalamic hamartomas (HHs) are developmental malformations occurring in the ventral hypothalamus. HHs are associated with neurological and endocrine disorders, including intractable seizures, cognitive impairment, behavioral disturbances, and central precocious puberty (Berkovic et al., 1988; Kerrigan et al., 2005). The epileptic syndrome in HH patients is characterized by laughing (gelastic) seizures, often beginning in early infancy. Most patients with gelastic seizures have a progressive natural history, and later develop additional seizure types and cognitive and psychiatric comorbidities (Berkovic et al., 1988; Prigatano et al., 2008). Seizures associated with HH are usually refractory to standard anti-epilepsy drugs, but surgical treatment can be effective (Mittal et al., 2013). Multiple clinical studies have demonstrated that HHs are intrinsically epileptogenic (Kuzniecky et al., 1997; Munari et al., 1995). However, cellular and molecular mechanisms underlying epileptogenesis within HH lesions remain incompletely understood (Wu et al., 2015). Gap junctions are cell-to-cell channel-forming structures formed by specialized proteins (connexins) in the plasma membranes of adjacent cells. They allow direct electrical coupling and chemical communication between almost all cell types in the central nervous system. Many different connexin proteins have been identified; most are specific for different cell types in the brain, including neurons and glia (Nakase et al., 2004; Rozental et al., 2000). Connexin-36 (Cx36) is predominantly expressed in gamma-aminobutyric acid-ergic (GABAergic) interneurons (Cruikshank et al., 2005; Sohl et al., 2005). In the rat, Cx36 shows a high level of buy Ganetespib in the hypothalamus, including the mammillary bodies (Condorelli et al., 2000). Gap junctions play an important role in locally synchronizing GABAergic neuron activity, including action-potential firing and sub-threshold changes in transmembrane potential resulting from inhibitory and excitatory post-synaptic potentials (Cruikshank et al., 2005). Gap junctions contribute to oscillating field potentials and enable GABAergic entrainment of principal (projection) neuron behavior within normal networks (Sohl et al., 2005). In view of these functional features, gap junctions likely contribute to the pathogenesis of epilepsy, particularly with respect to enhancing synchronous activity of neuronal subgroups within epileptic networks (Carlen et al., 2000; Dudek et al., 1998; Traub et al., 2004). This concept is supported by in vitro and in vivo epileptic animal models, in which the pharmacological blockade of gap junctions significantly reduces seizure occurrence (Carlen et al., 2000; Traub et al., 2004). Interictal epileptiform discharges (in the form of fast oscillations) can be abolished in freshly resected human epileptic tissue slices with carbenoxolone, a non-specific gap-junction blocker (Roopun et al., 2010). However, the understanding of gap junctions in human epileptogenesis is still limited and the potential for gap-junction blockers as therapeutic agents for human epilepsy remains effectively unexplored.
Materials and Methods
Results
Discussion How do these results contribute to the working model for epileptogenesis in HH tissue? Two predominant neuron phenotypes reside within HH tissue (Coons et al., 2007). The majority (approximately 90%) of HH neurons are small, round, monopolar or bipolar cells with local aspiny processes (Beggs et al., 2008; Coons et al., 2007; Kim do et al., 2008). These neurons express glutamic acid decarboxylase and project to symmetrical synapses; therefore, they are likely to be GABAergic interneurons (Beggs et al., 2008; Kim do et al., 2008; Wu et al., 2007; Wu et al., 2005). Small HH neurons occur in clusters that vary in size and abundance, but otherwise appear to be a universal feature of HH microarchitecture (Coons et al., 2007). Conversely, large HH neurons (approximately 10% of total) have a morphology consistent with projection-type cells, including a pyramidal shape, abundant Nissl substance, and multiple processes that are more highly branched and more likely to be spiny (Beggs et al., 2008; Coons et al., 2007; Kim do et al., 2008).