The nervous system is divided into two main sections, the central nervous system and the peripheral nervous system (Dahlstrand, Lardelli et al. 1995, Nieuwenhuys, Voogd et al. 2007). The central part consists of the brain and spinal cord, and the peripheral of sensory neurons, ganglia which are neurons providing connections between different neurological structures of the nervous systems, and nerves. Neurons and glial cells make up both the peripheral and central nervous systems, the
Chapter 6 Introduction
neurons being the main building unit of the nervous system (Pakkenberg and Gundersen 2011). Glia is a Greek word meaning ‘glue’ or ‘sticky’. Glial cells are important in preserving homeostasis, and myelin integrity, as well as providing support and protection for neurons in the brain. However, glial cells do not participate directly in the transfer of the neuronal signals. Glial cells outnumber neurons by about 10:1 depending on the brain region (Hilgetag and Barbas 2009). As well as supporting neurons, glial cells act as insulation for electric charges between neurons and neurotransmitters (Oligodenrocytes in the CNS and Schwann cells in the PNS, and supply neurons with vital nutrients. They also aid disposal of dead and damaged cells, and secrete factors for the growth of neurons (Jessen and Mirsky 2005).
This study focused on glial cells, especially astrocytes, which are the biggest glial cells in size. The following diagram summarizes the structure of the nervous system (figure 6-1).
Chapter 6 Introduction
6.1.1.1 The cortex
The cerebral cortex is neural tissue that surrounds the brain, representing the grey area of brain. The cerebral cortex is divided into left and right hemispheres, and is responsible for higher brain functions where information processing occurs (Smith, Fries et al. 2009). This region plays a key role in memory, attention, and integration of ideas in addition to language development, perception and awareness (Del Cul, Dehaene et al. 2009). It is a layered structure consisting of either three or six layers. The three layered areas, such as the olfactory cortex and hippocampus, represent phylogenetically older parts of the brain (Archicortex) while the neorcortex the most recently developed part consists of six layers, each of which has a different structure in terms of neurons and connectivity. The human cerebral cortex has a much larger surface area than other primates and ranges in thickness between 2–4 mm (Fischl and Dale 2000).
The cortical layers are called grey matter due to the fact that the brains in preserved material tend to be grey in colour, and consist of neurons and their unmyelinated fibers. Below this layer is the white matter, which is made up of myelinated axons. These connect neurons in the cerebral cortex with each other, as well as to nerve cells in other parts of the central nervous system.
The surface of the cerebral cortex is characterized by extensive folds. These folds or gyri are separated by grooves, called "sulci". The cortex can be split into several layers called phylogenetically, the neo-cortex (called iso-cortex), is distinguished into six horizontal layers. The hippocampus is one of the oldest parts of the cortex (also called archi-cortex), it has three cellular layers, and is divided into subfields. Neurons in various layers connect vertically to form small microcircuits, called columns. Different neocortical architectonic fields are distinguished by variations in the thickness of these layers, their predominant cell type and other factors such as neurochemical markers, Figure 6-2 shows the hippocampus and cerebral cortex in both human and mouse (Abeles 1991, Semendeferi, Armstrong et al. 2001).
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Figure 6-2 Diagram of the brain structure, illustrating differences in neuroanatomy between mice and humans.
Figure Shows hippocampus and cerebral cortex in both human and mouse. www.nature.com/nrd/journal/v4/n9/fig_tab/nrd1825_F2.html
6.1.1.2 The biology of the hippocampus:
The hippocampus is a major component of vertebrates and human brains, in particular. The term was derived from its curved shape in coronal sections of the brain, where the term contains two Greek words; (hippos) meaning ‘horse’ and (kampi) meaning ‘curve’. It plays an important role in linking information from short-term memory to long-term memory. It has extensive links with the cerebral cortex (Bliss and Collingridge 1993, Piekema, Kessels et al. 2006). Moreover, it is a fore brain structure, located under the cerebral cortex in mammals. In primates, the hippocampus is located in the medial temporal lobe, below the cortical surface. It contains two main interlocking parts; Ammon's horn and the dentate gyrus. In the dentate gyrus (DG), CA1 and CA3 fields are often referred to as the hippocampus proper. Both hippocampus and the dentate gyrus are representing the main parts of forebrain (Figure 6-3). Based on previous research, it is evident that the hippocampus is part of the brain system responsible for spatial memory and navigation (Gluck, Meeter et al. 2003, Kullmann 2011). Therefore, the hippocampus is a major target for research to find explanations for diseases of the central nervous system and
Cerebral cortex Thalamus Amygdala Hippocampus Hypothalamus Human brain Mouse brain
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Figure 6-3 Scheme of hippocampal with dentate gyrus layers in rodents.
Schematic illustration of the three layers of dentate gyrus area. The sub-granular zone of the dentate gyrus houses transit amplifying progenitor cells. These cells mature into neuroblasts, which migrate into the granule cell layer (GCL) and differentiate into granule neurons (Mature Granule Cell). The newly generated granule neurons allow interconnections by extending axonal projections along the mossy fiber towards the CA3, and into the molecular layer Mature. Cells receive glutamatergic inputs from the entorhinal cortex; GABAergic inputs from the interneurons and provide glutamatergic inputs to the CA3 neurons. The diagram adapted from from (Abrous, Koehl et al. 2005, McCaffery, Zhang et
al. 2006). P ro li fe ra ti o n M ig ra ti o n D if fe re n ti at io n CA1 CA2
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6.1.1.3 Dentate gyrus
The large number of small blood vessels that lie within the dentate gyrus give it a toothed appearance, thus called the dentate gyrus (DG) (Van Praag, Shubert et al. 2005). The dentate gyrus is part of the hippocampus, which is believed to be responsible for forming new memories (Neves, Cooke et al. 2008). It is characterized by its granular layer and it has three layers; molecular layer, granular layer (which gives granular shape to the DG and polymorphic layer. The CA3 pyramidal cells operate as a single auto-association network to store new episodic information. The dentate gyrus is important, mainly during learning, to help to produce a new pattern in the CA3 cells. Namely, the zone from the DG to CA3 is essential for the process of learning (Gilbert, Kesner et al. 2001). Therefore, some studies have been conducted to determine the ability of hippocampus to store new information as well as how quickly the CA3 auto-association system is operating during recall using modified synapses in pathways from the hippocampus to the cerebral cortex (Kesner 2007).
Chapter 6 Introduction