The brain is the central control organ of the nervous system in all vertebrates and most invertebrates. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all. In vertebrates, the brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing, balance, taste, and smell.
By Neuroanatomists the brain is considered to consist of six main regions: the telencephalon (cerebral hemispheres), diencephalon (thalamus and hypothalamus), mesencephalon (midbrain), cerebellum, pons, and medulla (Kandel 2000).
Each of these regions has a complex internal structure and some areas, such as the cortex or the cerebellum, are assembled of layers, folded or convoluted to fit within the available space. Other areas consist of clusters of many small nuclei. The medulla, for example, like the spinal cord, contains many small nuclei involved in a wide variety of sensory and motor functions. The hypothalamus is a small region at
Figure 2: Anatomy of the brain with its main regions indicated by different colors (adopted from The Anatomy of the Nervous System: From the Standpoint of Development and Function", by SW Ranson, WB Saunders, 1920)
Immunoproteasome assembly in the brain of LCMV-infected mice Introduction
the base of the forebrain and it is composed of numerous small nuclei, each of which has distinct connections and a distinct neurochemistry. The hypothalamus is the central control station for many homeostatic processes like controlling the circadian clock, control of eating and drinking, control of hormone release, and many other critical biological functions (Swaab 2003). Like the hypothalamus, the thalamus is a collection of nuclei with multiple functions: Some are involved in relaying information to and from the cerebral hemispheres, others are involved in motivation. The subthalamic area (zona incerta) seems to contain action-generating systems for several types of "consummatory" behaviors, including eating, drinking, defecation, and copulation (Jones 1985). The cerebellum modulates the outputs of other brain systems to make them more precise. Removal of the cerebellum does not prevent an animal from doing anything in particular, but actions become more hesitant and clumsy. This precision is not hereditary, but learned by trial and error. Learning how to ride a bicycle is an example of neural action that may take place predominantly within the cerebellum (Kandel 2000). The hippocampus is found only in mammals.
However, the area it derives from, the medial pallium, has counterparts in all vertebrates. There is evidence that this part of the brain is involved in spatial memory and navigation in fishes, birds, reptiles, and mammals (Salas et al. 2003). The basal ganglia are a group of interconnected structures in the forebrain, whose primary function seems to be action selection. They send inhibitory signals to all parts of the brain that can generate actions, and in the right circumstances can release the inhibition, so that the action-generating systems are able to execute their actions.
Rewards and punishments, for example, exert their most important neural effects within the basal ganglia (Grillner et al. 2005).
For the immunological context of this work the brain can be divided into 3 main compartments, which show distinctive properties concerning infectious susceptibility, immune privilege, and inflammation:
First there are the meninges, which represent a system of membranes that envelops the whole brain. It consists of an inner membrane, the pia mater, which firmly adheres to the surface and follows all the minor contours of the brain; the intermediate membrane, which is called the arachnoid membrane due to its spider-web like structure; and the outermost membrane, called the dura mater, which, strictly speaking, consists of two layers: the periosteal layer and the inner meningeal
Immunoproteasome assembly in the brain of LCMV-infected mice Introduction
layer. Like the arachnoid membrane the dura mater does not follow the convolutions of the brain surface and looks more like a loosely fitting sac encapsulating the brain.
The arachnoid membrane and the pia mater are sometimes together called the leptomeninges, and they are divided by the subarachnoid space, which is filled with cerebrospinal fluid (CSF).
The second immunologically interesting compartment is represented by the ventricles, which encapsulate the choroid plexus that is producing the cerebrospinal fluid (CSF). Previously the cerebrospinal fluid was regarded as an ultrafiltrate of plasma, but it is, in fact, actively produced by the secretory epithelium of the choroid plexus (CPE) (Strazielle and Ghersi-Egea 2000).
Finally, the third component is represented by the proper brain parenchyma, which consists of the white and the grey matter. The grey matter is the major component of the central nervous system. It consists of neuronal cell bodies, neuropil (dentrites and both myelinated and unmyelinated axons), glial cells, and capillaries. In contrast to the grey matter, which contains neuronal cell bodies, the white matter contains myelinated axon tracts (Purves 2008). The colour difference mainly arises from the whiteness of myelin. In living tissue, grey matter actually has a grey-brown colour, which comes from capillary blood vessels and neuronal cell bodies. Figure 3 gives an overview of the described compartments.
Figure 3: Immunologically relevant compartments of the brain.
The brain parenchyma is engaged in the CSF, which is produced by the choroid plexus, a specialized vascular organ within the ventricular system. CSF in the ventricles is continuous with CSF in the subarachnoid space between the inner and outer meninges.
Circumventicular organs such as the subfornical organ are brain regions lacking a blood-brain barrier (BBB) (adopted from Galea et al., 2006, Trends Immunol.).
Immunoproteasome assembly in the brain of LCMV-infected mice Introduction