A Study On The Dopamine Receptors And The Learning And Memory In The Marginal Division Of The 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 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,nuclear transcriptional factor pCREB 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.Dopamine (DA) is the most abundant catecholamine neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, cognition, emotion, positive reinforcement, memory and learning, andendocrine regulation. Disorder of the dopamine system has been linked with Parkinson's disease,Tourette's syndrome,schizophrenia, hyperprolactinemia and addiction. Dopamine plays role both in the physiology and pathology through its special receptors.Leaming and memory are the most advanced functions in brain.Learning is gaining and development of experiences(behavioral habits,perception,thought);Memory is keeping and reappearance of experience.Rescently,more and more studies have been focus on the effect of dopamine and its receptors on learning and memory.It has been proved that the marginal division of the striatum contains many dopamine fibers and terminals which imply that the DA might play an important role in the mechanism of learning and memory function of the marginal division.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.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.CREB is the most important nuclear transcriptional factor be related to the learning and memory,our study has show theexpression of phosphorylated CREB (pCREB) in the MrD of rat striatum immediately after Y-maze avoidance training.lt may be a nice indicator of learning and memory.This study was designed in the 2 aspects: l.the expression of dopamine receptors in the MrD of rat striatum. 2. An investigation on the mechanism of the signal transduction during avoidance learning and memory in the MrD.(l)the involvement of dopamine receptors in the expression of pCREB in the MrD immediately after Y-maze avoidance training; and (2) the influence on the long-term memory consolidation of Y-maze avoidance conditioning of a bilateral microjection of Dl receptor antagonist SCH-23390 into the MrD.Methods and ResultsChapter one:The expression of dopamine receptors in the MrD .The immunohistochemistry method was used to investigate the distribution of dopamine receptors in the marginal division of rat striatum using D1A and D2 receptors polyclone antibody. The D1A and D2 receptors were distributed more densely in the MrD than other part of striatum .Chapter two:An investigation on the mechanism of the signal transduction during avoidance learning and memory in the MrD.(l)The effect of SCH-23390 injected i.p.on the expression of pCREB in the MrD immediately after avoidance learning and memory training: Adult SD rats accepted intraperitoneal administration of SCH-23390 (1 mg/kg) or same volume of saline respectively immediately after spaced Y-maze avoidance training, and the expression of pCREB in the MrD was investigated with imrnunohistochemical technique 30 min later. The immunocytochemistry showed decreased expression of pCREB in the MrD of the SCH-23390 group comparing to the control group (P<0.01).(2)The effect of SCH-23390 microinjected into the MrD bilaterally on long-term consolidation of theavoidance task in Y-maze immediately after avoidance learning and memory training: The adult SD rats accepted intra-MrD microjection of SCH-23390 (1 u g /side) or same volume of saline respectively immediately following spaced Y-maze avoidance training, and the animals' performance on the Y-maze was investigated again 5 days after the treatments.The average correct run time of the SCH-23390 group in the Y-maze test was depressed significantly than that in the control group (p<0.05).Conclusions:Chapter onetThe expression of dopamine receptors in the MrD .The marginal division of the striatum contains the expression of dopamine receptors .Chapter two:A investigation on the mechanism of the signal transduction during avoidance learning and memory in the MrD.The positive expression of pCREB was observed obviously in the MrD of the adult SD rat striatum immediately after Y-maze avoidance training.The antagonist of dopamine Dl receptor SCH-23390 injected i.p. immediately after the training may significantly reduce the positive expression of pCREB in the MrD.The microinjection of SCH-23390 into the bilateral MrD immediately after the training may cause long-term memory deficit in the adult SD rats 5 days later.Based on the evidences mentioned above, it is reasonable to believe that the dopamine receptors are existed in the MrD ,and involved in the long-term consolidation of the avoidance task in Y-maze, and they may function as the membrane receptor in the mechanism of the signal transduction associated with the long-term memory formation in Y-maze avoidance task.