**1. Introduction**

Since the description by Scoville and Milner of profound anterograde amnesia in a patient known as H.M. following bilateral temporal lobe resection [1], the hippocampus and surrounding temporal lobe structures have been extensively studied for their role in memory. Subsequently, our understanding of the neurophysiological bases of hippocampal function was greatly enhanced by two breakthroughs: Bliss and Lomo's finding [2] of activity-dependent long-term potentiation (LTP) of synaptic transmission in the hippocampus, and the discovery of hippocampal place cells and neurons that encoded the spatial position of an animal reported by O'Keefe and Dostrovsky [3]. These discoveries stimulated researchers to study the types of memories related to the neural circuits of the hippocampus. Here, we discuss neural circuits and efferent or afferent fibers related to the hippocampus, including the entorhinal cortex to the hippocampus [4], hippocampus to the prefrontal cortex [5], and vDBChATs-dNGIs [6]. We also discuss LIS1, Fos, SynCAM1, BDNF, Smad3, Oxytocin, and DISC1, factors that influence memory insofar as they relate to the development of memory and memory consolidation. With recent technological advances, causal investigations of specific neural circuits relating to the hippocampus and Alzheimer's disease (AD) have helped us to understand the pathogenesis of AD and improve the clinical treatment of AD patients.

### **2. Cytoarchitecture and functional characteristics in the hippocampus**

The hippocampus is an elongated structure with a longitudinal axis extending in a C-shaped fashion, which can be functionally divided into dorsal, intermediate, and ventral parts [7, 8]. Along the transverse axis, it can be further divided into the CA1, CA3, and dentate gyrus (DG). There is a canonical trisynaptic pathway within the hippocampus, involving information proceeding from the entorhinal cortex (EC) to the DG, then to the CA3, and finally to the output node CA1 [9].

The DG has three layers, including the molecular layer, granule cell layer, and polymorphic cell layer [10]. The molecular layer mainly comprises dendrites of the dentate granule cells and the fibers of the perforant path that originate in the entorhinal cortex. The granule cell layer is the principal cell layer, which is largely composed of densely packed granule cells. The granule cell layer encloses a cellular region and forms the third layer of the DG, which is called the polymorphic cell layer. The DG plays a key role in learning, memory, and adult neurogenesis [11]. This region generates new neurons that are integrated into brain circuits [12].

The CA3 area is the largest in the hippocampus and forms the major route of information flow [13]. One of the most prominent features of the CA3 is that there are extensive interconnections among the principal cells via the circulating collateral fiber system [14]. The axon collateral branches of CA3 pyramidal cells form synapses with the apical dendrites of CA3 pyramidal cells in other regions and spread throughout most of the region to form an associative network [15].

The CA1 area, with its widespread projections, is a key output node of the hippocampal memory circuit, which transfers excitatory information out of the hippocampus proper via direct projections to deep layers of the EC or subiculum [16]. The CA1 is composed of densely packed large pyramidal neurons that play an important role in long-term memory and related spatial tasks and behavior [17]. Human CA1 pyramidal neurons exhibit distinctive morphological complexities, which have important computational implications [18]. Many additional functions have been proposed for the CA1, including novelty detection, input comparison, and enrichment of hippocampal output, possibly by redistributing information from the CA3 to a larger number of output neurons [19].

## **3. The hippocampus and memory**

Memory is the ability to use the past to serve the present or future. Without it, we are destined to enter the eternal present. In the twentieth century, Richard Simon introduced the term "engram" to describe the neural matrix used to store and recall memories [20]. Memory is actually a continuous process between nerve cells [21]. Essentially, a population of neurons is activated that undergoes persistent chemical and/or physical changes to become an engram; the neurons reactivate the engram by cues available at the time of the experience [22]. The criteria and experimental strategies in the study discussed by Morris and colleagues to evaluate synaptic plastic memory have become landmarks in evaluating the importance of the existence of engrams [23, 24].

The hippocampus is important for the storage and retrieval of declarative memories, including memories for perception, imagination, and recall of scenes and events [25, 26]. Studies have shown that spatial memory is closely related to the hippocampus. This is because the "place cells" in the hippocampus make the hippocampus necessary for spatial memory activities [27]. If the hippocampus is damaged, humans may not be able to remember where they have been and how to get to where they want to go. For example, AD is a progressive and neurodegenerative disorder of the cortex and hippocampus, characterized by progressive cognitive decline and

*Neural Circuits and Some New Factors Involved in Hippocampal Memory DOI: http://dx.doi.org/10.5772/intechopen.101309*

a prominent loss of hippocampal-dependent memory [28]. Degeneration of basal forebrain cholinergic neurons is a hallmark of AD. Its function depends on the nerve growth factor (NGF), which is transported retrogradely from the synthetic sites in the cortex and hippocampus [29]. Studies have found that patients with Parkinson's disease (PD) also experience a variety of nonmotor symptoms, the most important being cognitive impairment that in many cases can lead to dementia [30]. There is also evidence that the CA1, CA2–3, CA4-DG, and the subiculum are involved in the poor neurocognitive scores of PD memory caused by impairment. Furthermore, because the CA3 is essential for recall, it is expected that atrophy of the CA3 subregion will also affect the episodic memory recollection process in PD patients.
