• epilepsy
• glioma
• hyperexcitability
• peritumoral
• visual cortex

In recent years, the interaction between cancer cells and tumor microenvironment has emerged as one important regulator of tumor progression (Sanegre et al., 2020). Indeed, many evidences have shown that glioma cells cause changes in neural peritumoral tissue. For instance, it has been proved that glioma cells influence neighboring neurons inducing peritumoral dysfunctions (van Kessel et al., 2017b) such as the extrusion of high amount of glutamate, that eventually results in excitotoxicity and tumor invasion (Marcus et al., 2010; Rzeski et al., 2001b; Sontheimer, 2008b). In addition, it has been found that infiltrating glioma cells are able to perturb and impair the inhibitory cortical networks, altering the chloride homeostasis and provoking a consequent switch of gamma-aminobutyric acid (GABA) towards excitation (Campbell et al., 2015; Conti et al., 2011; D’Urso et al., 2012; Pallud et al., 2014; Tewari et al., 2018). In some cases, all these alterations can concur to promote the insurgence of comorbidity phenomena, such as epileptic seizures (Armstrong et al., 2016; Buckingham & Robel, 2013).
This thesis aimed at revealing the electrophysiological alterations induced by tumor growth. In order to address this issue, I performed a longitudinal visual evoked potential (VEP) analysis to monitor the neural cortical activity along with glioma progression in glioma bearing-mice. The data obtained revealed a progressive decay of the visual response. Moreover, I analyzed the LFPs recorded during blank stimuli (0% contrast) on each VEP recording session and I observed a enhancement of δ band together with a deterioration of α band during tumor growth; these data indicate that peritumoral tissue might reorganize itself increasing excitatory synapses and reducing the inhibitory networks.
Finally, through continuous EEG recordings, I observed that 80% of mice with glioma developed epileptic seizures, while 100% showed interictal events, indicating a marked hyperactivity of the peritumoral tissues.
Altogether, these evidence indicate that glioma causes dysfunctions on both excitatory and inhibitory peritumoral neural circuits and that the GL261 is a good model because reproduces both brain network impairments and hyperexcitability that occur in patients. Further studies are needed to shed new light on the molecular mechanisms that underlie this reorganization.