Overview Perhaps the major reason that neuroscience remains such an exciting field is the wealth of unanswered questions about the fundamental structure and functions of the human brain. To understand this remarkable organ (and the rest of the nervous system), the myriad cell types that constitute the nervous system must be identified, their interconnections traced, and the physiological role of the resulting circuits defined. Adding to these several challenges is the fact that a specialized anatomical vocabulary has arisen to describe the structure of the nervous system, as well as a specialized set of physiological terms to describe its functions. In light of these conceptual and semantic difficulties, comprehending the brain and the rest of the nervous system is greatly facilitated by a general picture of the organization of the nervous system, and by a review of the basic terms and anatomical conventions used in discussing its structure and function.
A flexure in the long axis of the nervous system arose as humans evolved upright posture, leading to an approximately 120° angle between the long axis of the brainstem and that of the forebrain (A). The consequences of this flexure for anatomical terminology are indicated in (B). The terms anterior, posterior , superior , and inferior refer to the long axis of the body, which is straight. Therefore, these terms indicate the same direction for both the forebrain and the brainstem. In contrast, the terms dorsal , ventral , rostral , and caudal refer to the long axis of the central nervous system. The dorsal direction is toward the back for the brainstem and spinal cord, but toward the top of the head for the forebrain. The opposite direction is ventral. The rostral direction is toward the top of the head for the brainstem and spinal cord, but toward the face for the forebrain. The opposite direction is caudal. (C) The major planes of section used in cutting or imaging the brain. To understand the spatial organization of these systems, some additional vocabulary employed to describe them needs to be defined. The terms used to specify location in the central nervous system are the same as those used for the gross anatomical description of the rest of the body ( Figure 1.9 ). Thus, anterior and posterior indicate front and back; rostral and caudal, toward the head and tail; dorsal and ventral, top and bottom; and medial and lateral, the midline or to the side. Nevertheless, the comparison between these coordinates in the body versus the brain can be confusing. For the entire body these anatomical terms refer to the long axis, which is straight. The long axis of the central nervous system, however, has a bend in it. In human and other bipeds, a compensatory tilting of the rostral/caudal axis for the brain is necessary to properly compare body axes to brain axes. Once this adjustment has been made, the other axes for the brain can be easily assigned. The proper assignment of these anatomical axes then dictates the standard planes for histological sections or tomographic images used to study the internal anatomy of the brain (see Figure 1.9C) . Horizontal sections are taken parallel to the rostral/caudal axis of the brain. Sections taken in the plane dividing the two hemispheres are sagittal , and can be further categorized as median and paramedian according to whether the section is near the midline (median or midsagittal) or more lateral (paramedian). Sections in the plane of the face are called frontal or coronal. Different terms are usually used to refer to sections of the spinal cord. The plane of section orthogonal to the long axis of the cord is called transverse , whereas sections parallel to the long axis of the cord are called longitudinal . In a transverse section through the human spinal cord, the dorsal and ventral axes and the anterior and posterior axes indicate the same directions. Tedious though this terminology may be, it is essential for understanding the basic subdivisions of the nervous system.
The central nervous system (defined as the brain and spinal cord) is usually considered to have seven basic parts: the spinal cord , the medulla , the pons , the cerebellum , the midbrain , the diencephalon , and the cerebral hemispheres ( Figure 1.10 ; see also Figure 1.8 ). The medulla, pons, and midbrain are collectively called the brainstem ( Box A ); the diencephalon and cerebral hemispheres are collectively called the forebrain . Within the brainstem are found cranial nerve nuclei that either receive input from cranial sensory ganglia via their respective cranial sensory nerves or give rise to axons that constitute cranial motor nerves ( Table 1.1 ). In addition, the brainstem is the conduit for several major tracts in the central nervous system. These tracts either relay sensory information from the spinal cord and brainstem to the midbrain and forebrain, or relay motor commands from the midbrain and forebrain back to motor neurons in the brainstem and spinal cord. Figure 1.10. The subdivisions and components of the central nervous system. (A) A lateral view indicating the seven major components of the central nervous system. (Note that the position of the brackets on the left side of the figure refers to the vertebrae, not the spinal segments.) (B) The central nervous system in ventral view, indicating the emergence of the segmental nerves and the cervical and lumbar enlargements. (C) Diagram of several spinal cord segments, showing the relationship of the spinal cord to the bony canal in which it lies.
Animal evolution has generated a wide range of species including single-celled animals and multicellular animals including invertebrates and vertebrates (left column, indicating time since common ancestor with humans). All of these animals show behavioural responses to their environment with vertebrates showing the most complex behaviours. Only the multicellular animals having anatomically specialised nerve cells forming their brains. The synapses that form the junctions between nerve cells are made of many proteins organised together into 'molecular signal processors' (middle column, Synapse protein complexity). In vertebrates and invertebrates, these proteins control psychological functions including learning and memory. Surprisingly, these synapse molecules exist in single-celled animals as a simple set of proteins (where they control response to environment), and this set was built upon to form a larger set used in the brains of invertebrates. This invertebrate set was expanded further in the brains of vertebrate species. The correlation between numbers of nerve cells in the brain of animals and the number of synaptic proteins shows that both contribute to the differences in species (right column). Complex synapses drove brain evolution One of the great scientific challenges is to understand the design principles and origins of the human brain. New research has shed light on the evolutionary origins of the brain and how it evolved into the remarkably complex structure found in humans. The research suggests that it is not size alone that gives more brain power, but that, during evolution, increasingly sophisticated molecular processing of nerve impulses allowed development of animals with more complex behaviours. The study shows that two waves of increased sophistication in the structure of nerve junctions could have been the force that allowed complex brains - including our own - to evolve. The big building blocks evolved before big brains. Current thinking suggests that the protein components of nerve connections - called synapses - are similar in most animals from humble worms to humans and that it is increase in the number of synapses in larger animals that allows more sophisticated thought. &quot;Our simple view that 'more nerves' is sufficient to explain 'more brain power' is simply not supported by our study,&quot; explained Professor Seth Grant, Head of the Genes to Cognition Programme at the Wellcome Trust Sanger Institute and leader of the project. &quot;Although many studies have looked at the number of neurons, none has looked at the molecular composition of neuron connections. We found dramatic differences in the numbers of proteins in the neuron connections between different species.&quot; This work leads to a new and simple model for understanding the origins and diversity of brains and behaviour in all species: we are one step closer to understanding the logic behind the complexity of human brains. Prof Seth Grant &quot;We studied around 600 proteins that are found in mammalian synapses and were surprised to find that only 50 percent of these are also found in invertebrate synapses, and about 25 percent are in single-cell animals, which obviously don't have a brain.&quot; Synapses are the junctions between nerves where electrical signals from one cell are transferred through a series of biochemical switches to the next. However, synapses are not simply soldered joints, but mini-processors that give the nervous systems the property of learning and memory. Remarkably, the study shows that some of the proteins involved in synapse signalling and learning and memory are found in yeast, where they act to respond to signals from their environment, such as stress due to limited food or temperature change. &quot;The set of proteins found in single-cell animals represents the ancient or 'protosynapse' involved with simple behaviours,&quot; continues Professor Grant. &quot;This set of proteins was embellished by addition of new proteins with the evolution of invertebrates and vertebrates and this has contributed to the more complex behaviours of these animals.&quot; &quot;The number and complexity of proteins in the synapse first exploded when muticellular animals emerged, some billion years ago. A second wave occurred with the appearance of vertebrates, perhaps 500 million years ago.&quot; One of the team's major achievements was to isolate, for the first time, the synapse proteins from brains of flies, which confirmed that invertebrates have a simpler set of proteins than vertebrates. Most important for understanding of human thought, they found the expansion in proteins that occurred in vertebrates provided a pool of proteins that were used for making different parts of the brain into the specialised regions such as cortex, cerebellum and spinal cord. Since the evolution of molecularly complex, 'big' synapses occurred before the emergence of large brains, it may be that these molecular evolutionary events were necessary to allow evolution of big brains found in humans, primates and other vertebrates. Behavioural studies in animals in which mutations have disrupted synapse genes support the conclusion that the synapse proteins that evolved in vertebrates give rise to a wider range of behaviours including those involved with the highest mental functions. For example, one of the 'vertebrate innovation' genes called SAP102 is necessary for a mouse to use the correct learning strategy when solving mazes, and when this gene is defective in human it results in a form of mental disability. &quot;The molecular evolution of the synapse is like the evolution of computer chips - the increasing complexity has given them more power and those animals with the most powerful chips can do the most,&quot; continues Professor Grant. Simple invertebrate species have a set of simple forms of learning powered by molecularly simple synapses, and the complex mammalian species show a wider range of types of learning powered by molecularly very complex synapses. &quot;It is amazing how a process of Darwinian evolution by tinkering and improvement has generated, from a collection of sensory proteins in yeast, the complex synapse of mammals associated with learning and cognition,&quot; said Dr Richard Emes, Lecturer in Bioinformatics at Keele University, and joint first author on the paper. The new findings will be important in understanding normal functioning of the human brain and will be directly relevant to disease studies. Professor Grant's team have identified recently evolved genes involved in impaired human cognition and modelled those deficits in the mouse. &quot;This work leads to a new and simple model for understanding the origins and diversity of brains and behaviour in all species&quot; says Professor Grant, adding that &quot;we are one step closer to understanding the logic behind the complexity of human brains.&quot; This research was a collaboration between scientists in the Wellcome Trust Sanger Institute, Edinburgh University and Keele University.
Figure 3.13. Saltatory action potential conduction along a myelinated axon. (A) Diagram of a myelinated axon. (B) Local current in response to action potential initiation at a particular site flows locally, as described in Figure 3.12 . However, the presence of myelin prevents the local current from leaking across the internodal membrane; it therefore flows farther along the axon than it would in the absence of myelin. Moreover, voltage-gated Na+ channels are present only at the nodes of Ranvier. This arrangement means that the generation of active, voltage-gated currents need only occur at these unmyelinated regions. The result is a greatly enhanced velocity of action potential conduction. Panel to the left of the figure legend shows the changing membrane potential as a function of time at the points indicated. Figure 3.14. Comparison of speed of action potential conduction in unmyelinated (upper) and myelinated (lower) axons. Increased Conduction Velocity as a Result of Myelination The rate of action potential conduction limits the flow of information within the nervous system. It is not surprising, then, that various mechanisms have developed to optimize the propagation of action potentials along axons. Because action potential conduction requires passive and active flow of current (see Figure 3.12 ), the rate of action potential propagation is determined by both of these phenomena. One way of improving passive current flow is to increase the diameter of an axon, which effectively decreases the internal resistance to passive current flow (see Box C ). The consequent increase in action potential conduction velocity presumably explains why giant axons evolved in invertebrates such as squid, and why rapidly conducting axons in all animals tend to be larger than slowly conducting ones. Another strategy to improve the passive flow of electrical current is to insulate the axonal membrane, reducing the ability of current to leak out of the axon and thus increasing the distance along the axon that a given local current can flow passively (see Box C ). This strategy is evident in the myelination of axons, a process by which oligodendrocytes in the central nervous system (and Schwann cells in the peripheral nervous system) wrap the axon in myelin , which consists of multiple layers of closely opposed glial membranes ( Figure 3.13 ; see also Chapter 1 ). By acting as an electrical insulator, myelin greatly speeds up action potential conduction ( Figure 3.14 ). For example, whereas unmyelinated axon conduction velocities range from about 0.5 to 10 m/s, myelinated axons can conduct at velocities up to 150 m/s. The major reason underlying this marked increase in speed is that the time-consuming process of action potential generation occurs only at specific points along the axon, called nodes of Ranvier , where there is a gap in the myelin wrapping (see Figure 1.4F ). If the entire surface of an axon were insulated, there would be no place for current to flow out of the axon and action potentials could not be generated. As it happens, an action potential generated at one node of Ranvier elicits current that flows passively within the myelinated segment until the next node is reached. This local current flow then generates an action potential in the neighboring segment, and the cycle is repeated along the length of the axon. Because current flows across the neuronal membrane only at the nodes (see Figure 3.13 ), this type of propagation is called saltatory , meaning that the action potential jumps from node to node. Not surprisingly, loss of myelin, as occurs in diseases such as multiple sclerosis, causes a variety of serious neurological problems ( Box D ).
Components Presynaptic terminal Synaptic cleft Postsynaptic membrane Neurotransmitters released by action potentials in presynaptic terminal Synaptic vesicles Diffusion Postsynaptic membrane Neurotransmitter removal When an impulse arrives at the end bulb , the end bulb membrane becomes more permeable to calcium . Calcium diffuses into the end bulb & activates enzymes that cause the synaptic vesicles to move toward the synaptic cleft. Some vesicles fuse with the membrane and release their neurotransmitter (a good example of exocytosis). The neurotransmitter molecules diffuse across the cleft and fit into receptor sites in the postsynaptic membrane. When these sites are filled, sodium channels open & permit an inward diffusion of sodium ions. This, of course, causes the membrane potential to become less negative (or, in other words, to approach the threshold potential). If enough neurotransmitter is released, and enough sodium channels are opened, then the membrane potential will reach threshold. If so, an action potential occurs and spreads along the membrane of the post-synaptic neuron (in other words, the impulse will be transmitted). Of course, if insufficient neurotransmitter is released, the impulse will not be transmitted. Impulse transmission - The nerve impulse (action potential) travels down the presynaptic axon towards the synapse, where it activates voltage-gated calcium channels leading to calcium influx, which triggers the simultaneous release of neurotransmitter molecules from many synaptic vesicles by fusing the membranes of the vesicles to that of the nerve terminal. The neurotransmitter molecules diffuse across the synaptic cleft, bind briefly to receptors on the postsynaptic neuron to activate them, causing physiological responses that may be excitatory or inhibitory depending on the receptor. The neurotransmitter molecules are then either quickly pumped back into the presynaptic nerve terminal via transporters, are destroyed by enzymes near the receptors (e.g. breakdown of acetylcholine by cholinesterase), or diffuse into the surrounding area. Source: http://www.franklincoll.edu/bioweb/bio120/week2.htm This describes what happens when an 'excitatory' neurotransmitter is released at a synapse. However, not all neurotransmitters are 'excitatory.' Structural features of a typical nerve cell (i.e., neuron) and synapse. This drawing shows the major components of a typical neuron, including the cell body with the nucleus; the dendrites that receive signals from other neurons; and the axon that relays nerve signals to other neurons at a specialized structure called a synapse. When the nerve signal reaches the synapse, it causes the release of chemical messengers (i.e., neurotransmitters) from storage vesicles. The neurotransmitters travel across a minute gap between the cells and then interact with protein molecules (i.e., receptors) located in the membrane surrounding the signal-receiving neuron. This interaction causes biochemical reactions that result in the generation, or prevention, of a new nerve signal, depending on the type of neuron, neurotransmitter, and receptor involved ( Goodlett and Horn 2001 ).
Types of neurotransmitters: 1- Excitatory - neurotransmitters that make membrane potential less negative (via increased permeability of the membrane to sodium) &, therefore, tend to 'excite' or stimulate the postsynaptic membrane 2 - Inhibitory - neurotransmitters that make membrane potential more negative (via increased permeability of the membrane to potassium) &, therefore, tend to 'inhibit' (or make less likely) the transmission of an impulse. One example of an inhibitory neurotransmitter is gamma aminobutyric acid (GABA; shown below). Medically, GABA has been used to treat both epilepsy and hypertension. Another example of an inhibitory neurotransmitter is beta-endorphin, which results in decreased pain perception by the CNS.
An active electrode placed on the vertex of the skull allows the recording of evoked auditory potentials from the auditory nerve and the brainstem (early potentials, waves I-V), and those of the higher auditory structures in the thalamo-cortex (late potentials). The brainstem evoked potentials (BAEPs), which have a short latency (<10 ms), are currently used clinically to test the auditory pathway up to the level of the inferior colliculus. See the diagram below for the association between the different waves making up the BAEPs and their related anatomical structures. Diagram illustrating the auditory pathway and the anatomical locations related to the the different waves of the BAEP.- auditory nerve = wave I - cochlear nuclei = wave II- superior olive = wave III- lateral lemniscus = wave IV - inferior colliculus = wave VWaves I-V make up the brainstem AEP. The thalamus (medial geniculate ganglion) and the auditory cortex (temporal lobe) make up the middle and late waves of the AEP.