3). This reduction in anxiety levels may be related to

prevention of neurodegeneration, especially in limbic system areas, such as hippocampus, thalamus and amygdala (Fig. 1). Hippocampus projects to the prefrontal cortex and has some closely connected reciprocal projections to amygdala (Bannerman et al., 2004). Thus, both hippocampal and amygdalar lesions observed after SE, may potentially be accountable by altered emotionality of animals, mainly by strong connectivity between these two limbic structures which may have an important role in brain processes associated with anxiety-like behaviors (Bannerman et al., 2004). In addition to that, thalamocortical axonal projections are responsible for conveying peripheral sensory stimuli to primary sensory cortex (Wimmer et al., 2010). KU-60019 in vivo Current studies (Meyer et al., 2010a, Meyer et al., 2010b and Wimmer et al., 2010) show that ventral posteromedial thalamic nucleus (VPM) and posteromedial nucleus (POm) projections establish vertical axon bundles in the vibrissal cortex through two separate pathways, lemniscal (projection arising from VPM cells) and paralemniscal (projection from POm cells) (Jones, 2002). These two pathways can regulate the same neurons in vibrissal cortex simultaneously (Wimmer et al., 2010). The elevated

neuronal loss induced by SE in VPM could disrupt these regulatory processes, leading to changes in vibrissae perception, and, consequently, elevating the expression of anxiety-like behaviors in EPM task. Nevertheless, even if ketamine post-SE onset treatment PI3K inhibitor has completely avoided neurodegeneration, the anxiety-like behaviors found in these animals were only partially prevented,

Paclitaxel chemical structure suggesting that SE can induce behavioral changes independently of neuronal death. Previous works using a model of febrile seizures found physicochemical alterations in hippocampal and amygdalar neurons which were not accompanied by significant DNA fragmentation (Bender et al., 2003, Chen et al., 2001 and Dube et al., 2000). In addition, Hoffmann et al. (2004) observed cognitive impairment in the water maze test in the LiCl–pilocarpine model even in absence of cell loss. In our study, ketamine-blockage of NMDAR in non-SE young rats resulted in enhanced anxiety levels later in life, which adds further support to the hypothesis that emotional behavioral changes can occur separately of neuronal death. Long-term consequences, such as altered emotionality, caused by ketamine in non-SE rats can be related to ketamine influence on physiological pathways. Blockage of NMDAR in normal conditions can affect physiological processes such as long-term responses and neural plasticity. A recent study observed pro-oxidant effects of ketamine on the central nervous system after a single ketamine administration which may be related to anxiety-like behaviors (da Silva et al., 2010).