Preface

It has been more than 400 years since the hippocampus was first described. As early as 1578, Arantius described the processes at the bottom of the temporal angle as the hippocampus. Based on the ventricular morphology, in 1732 Winslow suggested using the noun "ram horn" for the structure. In the same period, De Garengeot used the term Cornu Ammonis for the hippocampus, referring to the Egyptian god Amun, who has the head of a ram. Research has made the structure and function of the hippocampus clearer and clearer, but there are still many unknown secrets.

The hippocampus is a bicortical structure composed of the Cornu Ammonis and dentate gyrus. They are interlaced with each other, and separated from each other, bounded by the hippocampal sulcus. The hippocampus belongs to the oldest part of the evolution of the brain, namely, the paleocortex. The Cornu Ammonis has three layers: the molecular, pyramidal, and pleomorphic layers. The cortex of the dentate gyrus is also divided into three layers: the molecular, granular, and pleomorphic layers. In the granular cell layer, the marginal area near the hilus is called the subgranular layer, where in the 1960s and 1970s it was found that there are neural stem cells with self-renewal and multi-differentiation potential in adult mammals. The subgranular layer is one of the few areas of the nervous system where postnatal neurogenesis occurs. Studies have shown that the dentate gyrus of primates still retains proliferative precursor cells in adulthood, but few in the aged. Therefore, the hippocampus has the ability of neurogenesis, and the existence of neural stem cells also provides a basis for hippocampal structure and functional plasticity.

There are extensive fiber connections between the hippocampus and other brain regions. The afferent fibers of the hippocampus mainly include perforating fibers from the entorhinal cortex and septal-hippocampal fibers from the septal nucleus. The fimbria fornix is the main efferent pathway of the hippocampus. In addition to terminating the mammillary body, there are fibers ending in the cingulate gyrus, septal nucleus, preoptic area, lateral hypothalamic area, anterior thalamic nucleus, and so on. Because of these connections, the hippocampus is involved in a variety of functions, such as learning, memory, attention, emotion, sensory information processing, and motor function. The hippocampus plays a crucial role in learning and memory, involving all aspects of narrative memory. Information from the neocortex converges to the entorhinal region and then further reaches the hippocampus. Therefore, the newly acquired information is filtered through the hippocampus before reaching the neocortex. The hippocampus can judge whether it is new or recent information, and the identification of old information mainly depends on the neocortex.

The first part of this book consists of four chapters that introduce the cytoarchitecture and functions of the hippocampus. Chapter 1 by Jing et al. describes the learning and memory-related circuits and fiber connections of the hippocampus. Chapter 2 by Bastos et al. states the correlation between fiber autofluorescence and postsynaptic zinc dynamics of pyramidal CA3 neurons. Chapter 3 by Luo et al. focuses on the pattern formation process of entorhinal cortex grid cells. Chapter 4

by Burman demonstrates the influence of the hippocampus across a variety of cognitive domains.

Hippocampal injury can lead to obvious neurological and mental diseases such as Alzheimer's disease (AD), epilepsy, and so on. AD is a latent progressive neurodegenerative disease. Clinically, it is characterized by comprehensive dementia such as memory impairment, aphasia, apraxia, agnosia, and impairment of visuospatial skills. The characteristic pathological changes include atrophy of the hippocampus and cerebral cortex with β-amyloid deposition, neurofibrillary tangles, and loss of neurons. Hippocampal atrophy is associated with early memory impairment, which indicates the possible occurrence of AD. Acetylcholine (ACh) and choline acetyltransferase (ChAT) in the hippocampus and neocortex of AD patients is decreased significantly, which is considered to be one of the causes of memory and cognitive impairment. At present, there is no specific treatment or reversal of disease progression.

The second part of this book focuses on hippocampal-related diseases, including their pathogenesis and treatment. Chapter 5 by Chu and Liu introduces the role of tau protein in physical conditions and the pathological changes related to neurodegenerative diseases, as well as the treatment research based on tau. Chapter 6 by Xu et al. describes the role of TREM2 and microglia in the occurrence and development of AD. Chapter 7 by Wen and Guohua summarizes AD-related circRNAs. Chapter 8 by Jara et al. focuses on the effects of red-light transcranial LED therapy on agerelated hippocampal memory. Chapter 9 by Jiang et al. discusses experimental and clinical research using stem cells to treat AD. The stem cells involved include embryonic stem cells, neural stem cells, mesenchymal stem cells, induced pluripotent stem cells, and others. Finally, Chapter 10 by Vafaei-Nezhad et al. talks about the effects of maternal diabetes on multiple brain regions including the hippocampus before and after birth.

I am honored to have had the chance to work on this book with more than thirty authors. In this book, we attempt to provide the basics of hippocampal physiological function, cytoarchitecture, circuits, diseases, and treatment. I'd like to thank the staff IntechOpen, particularly Ms. Maja Bozicevic, who coordinated the publication of this book with great patience and encouragement. We hope this book will be useful for readers interested in hippocampal formation, disease, and treatment.

> **Xinhua Zhang** Medical College of Nantong University, Nantong, China

Section 1
