With a few important exceptions, all the neurons in the mammalian nervous system fall into two major classes: excitatory neurons, using glutamate as a neurotransmitter, and inhibitory neurons, using GABA (and in some regions also glycine) as a neurotransmitter. GABAergic neurons play the critically important roles of counterbalancing excitation and of channeling the flow of sensory and motor information in time and in space; loss of cortical GABAergic neurons or impairment of their function is a major factor underlying epilepsy and degenerative motor diseases. Their critical roles notwithstanding, GABAergic neurons remain poorly understood; in most regions they are interspersed among the more numerous excitatory neurons, and studying them has been seriously hampered to date by the lack of a means to identify them reliably in living tissue. The need addressed by the proposed study is for a novel method to identify and visualize GABAergic neurons in living preparations. We have recently made the first step towards addressing this need, by generating several lines of transgenic mice in which expression of green fluorescent protein is driven in a cell-specific manner in putative GABAergic neurons. These lines are potentially an extremely powerful research tool for studying GABAergic neurons in living preparations; however before they can be used for such studies, the molecular genetics of the transgene needs to be characterized, the fidelity of GFP expression in GABA neurons needs to be validated, and normal GABAergic function should be verified. Once these aims are accomplished, the mice will be made available to the scientific community through the NIH-sponsored Mutant Mouse Regional Resource Centers. The Exploratory/Developmental R21 Grant mechanism of support is appropriate, because the proposed project will demonstrate the validity and feasibility of a new tool, the GAD67-GFP transgenic mouse, which could have a major impact on the field of neuroscience by allowing investigators to address crucially important questions regarding GABAergic neurons, questions which were so far difficult or impossible to address.
| Ma, Yunyong; Hu, Hang; Berrebi, Albert S et al. (2006) Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J Neurosci 26:5069-82 |
