Brain structural and functional abnormalities are a continuum in epilepsy. Neuronal diversity and functional spatiotemporal dynamics in the network are key points in establishing the normal connectivity in the brain that develops through a sequence of coordinated events and electrical activity. Pyramidal neurons have considerable connectional and processing complexity in brain circuits. These highly specialized neurons in the network also show vulnerabilities and can contribute to epileptogenesis. Pyramidal cells are crucial but not the only cells participating in hyperexcitability; glial cells are also important for synaptic plasticity during epileptogenesis. In addition, GABAergic interneurons are implicated in different aspects of ictogenesis and epileptogenesis. GABAergic synapses at different pyramidal cell domains and vice-versa, coordinated by synapse-driven activity patterns, contribute to spontaneous network oscillations in the brain. A large diversity of cells operates in intricate circuits formed by synapses at distinct cellular domains and at different times to encode, process, store, and send information, contributing to marked synaptic remodeling. Aberrant morphology, synaptic organization, and plasticity of the neuronal network, can recruit distinct microcircuits at different locations at specific times, which could alter synchronicity, inducing abnormal oscillations and consequent behavior, resulting in epilepsy and neuropsychiatric disorders.