Studies On The Mechanism Of The Avoidance Learning And Memory Function In The Marginal Division Of Rat Striatum

The marginal division of the striatum (MrD) is a newly identified structure at the caudal most edge of the neostriatum of the rat brain. It was firstly discovered by Shu et al in 1987. The MrD was also successively observed in the brains of cat, monkey and human. Many neuropeptides densely packed in the fibers, terminals and neuronal somata of the MrD. It has structural and/or functional connections with many learning and memory related brain areas including hippocampus, amygdala, basal nucleus of Meynert (NBM) and prefrontal cortex. Thus, MrD is distinguished from the rest of the stiratum by spindle-shaped neurons, special connections and intensely expressed many neurotransmitters and related receptors. Functionally, MrD was proved to be involved in learning and memory function of rat brain by a double blinded Y-maze avoidance task. The expression of immediate-early genes c-fos and c-jun was observed in the MrD of rat striatum immediately after the Y-maze avoidance training. The MrD was proved involving in the auditory digital working memory in human. Lesions in human MrD might cause disorder of cognitive function. However, the mechanism of the signal transduction in the MrD during learning and memory is not clear. It is unknown that whether there are differences between the MrD and other memory-related brain areas especially hippocampus in the learning and memory functions of the brain. Learning and memory function are the most important and fundamental mental processes of the brain. At present, the hippocampus and other brain areas e.g. the medial temporal lobe memory system, prefrontal cortex, diencephalon, amygdala, cerebellum and NBM have been found to be involved in learning and memory in succession. These memory -related centers were not only thought to play different roles-9-in learning and memory function of the brain, but there were close functional and structural connections among them. Thus, the solution of the above two problems could contribute to know the mechanism of learning and memory function on cellual and molecular level in the MrD, and the relationship between the MrD and other memory-related centers in the learning and memory function of the brain.The cAMP responsive element binding protein (CREB) is a important nuclear protein. This transcription factor is a key component of intracellular signaling events that regulate a wide range of biological functons including leraning and memory. Evidences from Aplysia, Drosophila, mice, and rats showed that CREB-dependent transcription is required for the cellular events underlying long-term but not short-term memory. CREB may be a key modulater of processes required for long-term memory formation. The phosphorylation of Ser 133 is a critical step in CREB activaton. The putative CREB target genes were observed over 100, including genes that control neurotransmission, cell structure, signal transduction, transcription, and metabolism et al. The glutamate is most abounded among the excitatory amino acid in the central nervous system. It is the major excitatory neurotransmitter in the brain. And it has be proved that the N-methyl-D-aspartate (NMDA) subtype of glugamate receptors in the mammalina brain plays a central role in synaptic plasticity underlying refinement of neuronal connections during development, or processes like long-term potentiation (LTP), learning and memory.As mentioned above, we have proved that the MrD was involved in learning and memory function of rat brain by a double blinded Y-maze avoidance task. The expression of immediate-early genes c-fos and c-jun was observed in the MrD of rat striatum immediately after the Y-maze avoidance training. It was showed that mRNA of NMDA receptor subnits of NR1, NR2A and NR2B proteins were expressed in the MrD of rat striatum. In thepart one of this study, to investigate role of the membrane receptor and nuclear transcriptional factor in the mechanism of signal transduction in MrD within the process of long-term memory consolidation by Y-maze avoidance task, the study was designed i...