The gene knockout technology for the analysis of learning and memory, and neural development

Publisher Summary Using the gene knockout technology, this chapter presents an analysis of learning and memory, and neural development. It investigates the molecular substrates of synaptic plasticity by producing mice that lack the γ isoform of Ca 2+ /phospholipid-dependent-protein kinase (PKCγ) using the embryonic stem (ES) cell gene targeting technology. PKC constitutes a family of isoenzymes involved in signal transduction pathways in diverse systems. This enzyme was chosen for the study reviewed in the chapter because pharmacological studies have repeatedly implicated PKC as playing a role in long-term potentiation (LTP). To re-examine the role of N -methyl-D-aspartate (NMDA) receptor (NMDAR)-mediated activity in the establishment of neural patterns in the whisker-to-barrel system, reverse genetics is used to selectively “knock out” the NMDAR1 subunit of the NMDA receptor. The results from this examination show that in the knockout animals, although central targeting and topographic projection of trigeminal afferent appear to be normal and postsynaptic neurons are responsive to the stimulation of primary trigeminal afferent, whisker-specific neural patterns fail to develop in the absence of the NMDA receptor.