Functional Organization of the Hippocampal Formation

描述（由申请人提供）：海马体形成是大脑内侧颞叶记忆系统的重要组成部分，该系统允许个体对其生活事件的信息进行编码。对于在成熟的大脑中调节这一功能的连接网络，我们知道的很多。齿状回、海马体和托下通过穿孔通路接受来自内嗅皮层的主要输入。这很可能是情景记忆形成的“原材料”。而内嗅皮层则与几个多感觉皮层区域有明显的双向联系，其中包括嗅周、海马旁和脾后皮层。这种神经解剖学表明，海马体主要使用高度加工的多感觉信息来制造记忆，并可能将编码信息存储在这些相同的多感觉皮层中。对任何物种的海马形成发育的研究都非常少，对人类和非人类灵长类动物的研究就更少了。如果这些信息是可用的，它可能会提供一些见解，为什么人类通常无法记住他们三岁之前的生活情节。在妊娠19-22周时，可以观察到人类海马体和枕骨下的内嗅投射（Hevner和Kinney， 1996），尽管没有证据表明纤维投射的成熟模式是何时形成的。在之前的资助期间，我们证明了在新生恒河猴身上建立了一种基本的成年模式的穿孔路径连接。我们现在建议将这些研究扩展到胎儿大脑，以确定穿孔路径何时在恒河猴中首次建立，以及何时以及如何成熟为成年模式。我们现在也准备开始分析正在发育的人类海马体的形成，这方面的信息非常有限。我们建议将我们的非人类灵长类动物研究扩展到人类大脑，通过对整个生命周期中海马形成的细胞数量和体积增加进行定量的立体分析。最后，我们建议通过对发育中的恒河猴的大脑进行纵向磁共振成像（MRI）分析，然后对其记忆能力进行行为评估，从而启动一个新的恒河猴出生后海马形成的结构/功能分析项目。我们之前发现，正常发育儿童的海马体总量在4.5到6.5立方厘米之间，这些儿童的海马体大小与他们的智商密切相关。这表明，海马体越大，记忆力越好。但是，一个人的海马体是天生的更大，还是海马体受益于丰富的成长环境？另外，如果一个个体的海马体更大，是因为有更多的神经元，还是神经元有更复杂的连接？我们将使用恒河猴模型来探索这些先天/后天的问题。

DESCRIPTION (provided by applicant): The hippocampal formation is an important component of the brain's medial temporal lobe memory system that allows individuals to encode information about episodes of their lives. Much is known about the network of connections that mediates this function in the mature brain. The dentate gyrus, hippocampus and subiculum receive major inputs from the entorhinal cortex via the perforant path. This is likely the "raw material" from which episodic memories are made. The entorhinal cortex, in turn, has prominent bidirectional connections with several polysensory cortical regions prominently including the perirhinal, parahippocampal and retrosplenial cortices. This neuroanatomy suggests that the hippocampus makes memories mainly using highly processed, multisensory information and likely stores the encoded information in these very same polysensory cortices. There are remarkably few studies of the development of the hippocampal formation in any species, and even fewer in man and in the nonhuman primate. If this information were available, it might provide some insights into why humans are typically unable to remember episodes of their lives prior to three years of age. Entorhinal projections to the human hippocampal fields and subiculum are observed by 19-22 weeks of gestation (Hevner and Kinney, 1996) though there is no available evidence concerning when the mature pattern of fiber projections is developed. During the previous funding period, we demonstrated that an essentially adult pattern of perforant path connections is established in the newborn rhesus monkey. We now propose to extend these studies to the fetal brain to determine when the perforant path is first established in the rhesus monkey and when and how it matures to an adult pattern. We are also now prepared to start an analysis of the developing human hippocampal formation for which there is only very limited information. We propose to extend our nonhuman primate studies to the human brain by carrying out quantitative, stereological analyses of cell number and volume increases of the hippocampal formation throughout the lifespan. Finally, we propose to initiate a new program of structure/function analyses of the postnatally developing hippocampal formation in the rhesus monkey by carrying out a longitudinal magnetic resonance imaging (MRI) analysis of the brains of developing rhesus monkeys followed by behavioral assessments of their memory capacity. We had previously found that the total volume of the hippocampus in typically developing children ranges in size from 4.5 cm3 to 6.5 cm3 and that the size of the hippocampus in these children was strongly correlated with their IQ. This would suggest that a larger hippocampus predicts better memory function. But, is one born with a larger hippocampus or does the hippocampus benefit from an enriched upbringing? Also, if an individual hippocampus is larger, is this because there are more neurons, or neurons that have more elaborate connections? We will explore these nature/nurture questions using the rhesus monkey model.