| Learning and memory function are one of the most important, and fundamental mental processes of the brain. The engram is the representation of a memory in the brain. The localization of the engram in the brain is intensively studied in the fields of neuroscience, psychology and psychiatry. After Scoville and Milner reported a persistent impairment of recent memory caused by bilateral medial temporal lobe resection in man in 1957, the hippocampus and other brain areas, e.g. the medial temporal lobe memory system, prefrontal cortex (PFC), amygdala, and basal nucleus of Meynert (NBM), were successively thought to be involved in learning and memory. The marginal division of the striatum (MrD) is a newly identified structure at the caudal most edge of the neostriatum, near the rostral border of the globus pallidus, in the brain of the rat, discovered by Shu et al in 1988. The MrD is distinguished from the rest of the striatum by consisting of spindle-shaped neurons, special connections, and intensely expressed neurotransmitters in the fibers, terminals, and neuronal somata. The MrD was also identified in the brains of cat and monkey. It was proved to be involved in learning and memory function of rat brain by a double blinded Y-maze behavioral test and c-fos expression experiment. However, whether there is a MrD in human striatum is still undiscovered. And if there is a MrD in human brain, does it have the function of learning and memory? What is the role of the MrD in neuronal memory circuits?In these studies, firstly, the existence and the immunohistochemistry properties of the MrD in human brain were proved and demonstrated with Nissl stain and immunohistochemical methods. Secondly, the involvement of the human MrD in learning and memory was investigated with a functional magnetic resonance imaging (fMRI) experiment. It is proved that the MrD was involved in auditory digital working memory in human. Then clinical cases with MrD lesions were investigated, combining MRI and cognitive function analyses with Mini-Mental State Examination (MMSE), to explore in clinic whether the MrD is involved in the cognitive function of humanbrain. The learning and memory function of the MrD was then verified by clinic investigations. Finally, the role of the MrD in neuronal memory circuits was discussed according to the nervous auxology of the MrD, blood supply of the MrD, the functional and structural connections between the MrD and other memory-related structures, and the influence of these connections on learning and memory function.Part I Study on the structure of human MrDThe MrD in the rat, cat and monkey brains consist of fusiform neurons and is densely packed by SP, L-ENK, NT, SOM and TH positive somata and fibers. To demonstrate the existence of the MrD in the human striatum, the cytoarchitecture and distribution of neurotransmitter in the human striatum were studied using Nissl stain and immunohistochemistry. In the Nissl stained section, there is a distinct fusiform cell zone between the putamen and globus pallidus of the human striatum. The long axes of these neurons were running dorsoventrally, parallelly to the medial border of the putamen. Numerous SP, L-ENK, NT, SOM and TH positive fibers and terminals and some L-ENK, NT positive cells were found in this area. The results proved the existence of the MrD in the striatum of human brain, as well as in the rat, cat and monkey brains. The shape of the neurons and the distribution of the neuropeptides in human MrD are also similar to the rat, cat and monkey MrD. It is indicated that the MrD is a common structure in mammalian brains. The MrD is much thicker in higher mammalians, which suggested that the MrD is a developing structure in the evolution. We inferred that the MrD might have important function in human brain. Then the function of human MrD was investigated in healthy volunteers using fMRI technique.Part II Study on the function of human MrDThe MrD was identified to be involved to learning and memory function of the rat brain by behavio...
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