Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and to refine the final number of neurons for a functional neuronal circuit. The tumour suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, aberrant hyperproliferative signals or cellular stress. Meanwhile p53 is largely expressed in progenitors’ cells during development, in adult mice p53 expression is restricted to the neurogenic niches where it regulates cell proliferation and self-renewal. To investigate the functional consequences of p53 deletion in the cortex and hippocampus, we generated a conditional mutant mouse (p53-cKO) in which p53 is deleted from pallial progenitors and their derivatives. We did not find any significant change in the number of neurons in the mutant cortex and or CA region of the hippocampus compared with control mice. However, p53-cKO mice present more proliferative cells in the subgranular zone of the dentate gyrus and more granular cells in the granular cell layer. Glutamatergic synapses in the CA3 region are increased in p53-cKO mice compared with control littermates, which triggers overexcitability and an increase in epileptic susceptibility in the mutant mice.