Neural plasticity is expressed through exquisite control of excitability. The neocortex and hippocampus are among the most plastic structures in the central nervous system that require precise homeostatic regulation to maintain normal brain activity. Loss of this regulatory control can lead to seizures and epilepsy. The link between neuronal plasticity and epilepsy is interesting, since most seizures involve neocortex and hippocampus. The Ramirez laboratory employs acute and organotypic slice cultures of the neocortex and hippocampus from mice to study intrinsic membrane properties (van Drongelen et al. 2003, 2006) and homeostatic regulation of synaptic transmission (Trasande and Ramirez, 2007; Koch et al. 2010). Organotypic slice cultures from the neocortex spontaneously generate up and down states under control. We demonstrate that inflammatory processes and inactivity can lead to upregulation of excitatory synaptic transmission, cell death and paroxysmal depolarization shifts
Click here for a movie that shows a seizure like state recorded with calcium imaging in a neocortical slice after activity deprivation. We are interested in characterizing mechanisms that lead to the break-down of homeostatic control and the change in the set-point of homeostatic regulation in neocortical networks to understand how for example traumatic brain injury leads to the development of seizure activity. We are also interested in understanding how changes in the set-point of homeostatic regulation lead to intractable seizures.