Laboratory of molecular neurobiology (1988-1994)

Abstract

While Dr. Costa was the Director of FGIN he became interested in the regulation of genes encoding various neurotransmitter receptors. More specifically, there was increasing evidence supporting a role for tetanic stimulation of the NMDA-subtype of ionotropic glutamate receptors in the development of long term potentiation and long term depression. Moreover, the protein products of the immediate early gene family, such as c-fos and c-jun, were known modulators of downstream signaling events that facilitated changes in neuronal transcriptomes in response to incoming afferent stimulation. The immediate early gene products were known transcriptional factors that activated gene expression in response to excitatory stimulation. In fact, the expression of c-fos/c-jun was often used to map neuronal circuits linked through a common initiation point such as occurs in focally-evoked seizures. Dr. Costa firmly believed that excitatory and inhibitory transmission was balanced in the central nervous system and that this might come about through changes in the expression of the genes encoding these neurotransmitter receptors. In other words, persistent stimulation of NMDA receptors would be expected to increase expression of the inhibitory GABAA receptors to accommodate the increased excitation. That this receptor crosstalk might occur through the products of the immediate early genes was testable and the focus of the Molecular Neurobiology Laboratory from 1988 to 1994. In a broader sense, stimulation of ionotropic NMDA-selective glutamate receptors has been associated with numerous downstream molecular and cellular processes. How these processes are linked to changes in gene expression has been the focus of studies in the neurosciences for many years.