Synaptopodin (SP) is localized within the spine apparatus, an enigmatic structure located in the neck of spines of central excitatory neurons. It serves as a link between the spine head, where the synapse is located, and the endoplasmic reticulum (ER) in the parent dendrite (Vlachos et al. 2009, Korkotian and Segal, 2011, Zhang et al. 2013). SP is also located in the axon initial segment, in association with the cisternal organelle, another structure related to endoplasmic reticulum. Extensive research using SP knockout (SPKO) mice suggests that SP has a pivotal role in structural and functional plasticity (Deller et al. 2003, Deller et al. 2007). Consequently, SPKO mice were shown to be deficient in cognitive functions, and in ability to undergo long term potentiation of reactivity to afferent stimulation (Deller et al. 2003). In contrast, neurons of SPKO mice appear to be more excitable than their wild type (wt) counterparts(Bas Orth et al, 2007). To address this discrepancy, we have now recorded activity of CA1 neurons in the mouse hippocampus slice, with both extracellular and patch recording methods. Electrophysiologically, SPKO cells in CA1 region of the dorsal hippocampus were more excitable than wt ones. In addition, exposure of mice to a complex environment caused a higher proportion of arc-expressing cells in SPKO than in wt mice hippocampus. These experiments indicate that higher excitability and higher expression of arc staining may reflect SP deficiency in the hippocampus of adult SPKO mice.