L8_CNS Nervous System PDF

BIOLS312F Nervous System DR EMILY WONG 1 The Nervous System 2 The Nervous System has two major divisions: ◦ The Central Nervous System (CNS), which is composed of the brain and spinal cord. ◦ The Peripheral Nervous System (PNS) is composed of the nerves that connect the brain or spinal cord with the...

BIOLS312F Nervous System DR EMILY WONG 1 The Nervous System 2 The Nervous System has two major divisions: ◦ The Central Nervous System (CNS), which is composed of the brain and spinal cord. ◦ The Peripheral Nervous System (PNS) is composed of the nerves that connect the brain or spinal cord with the body’s muscles, glands, and sense organs. The neuron is the basic cell type of both systems. 3 Structure of a Neuron 4 Neurons These are the “nerve cells”. They are amitotic, so they do not divide. They also have a very high metabolic rate. Clusters of cell bodies in the CNS are called nuclei. Neurons are not the most numerous cell in the CNS; Glial cells are. Regardless the types of neurons, they can transmit impulses at speed of up to 200 metres per second. 5 Functional Classes of Neurons 6 7 Glial Cells of the CNS The glial cells in the CNS are: Astrocytes: support cells, control extracellular environment of neurons Microglia: “immune system” of the CNS Ependymal cells: ciliated, involved with production of CSF and CSF movement Oligodendrocytes: responsible for the myelin formation 8 Glial Cells 9 Glial Cells of the PNS Schwann cells surround and form myelin sheaths around the larger nerve fibers. These are vital to regeneration and proper nerve signal conduction. 10 Schwann Cells & Myelin 11 Synapses Synapses can use both chemical and electrical stimuli to pass information. Synapses can also be inhibitory or excitatory depending on the signal/ neurotransmitter being transmitted. 12 Recap Basic Principles of Electricity 13 Recap Membrane Potentials Voltage difference between inside and outside of a cell Different cells have different resting membrane potentials. Neurons have a resting membrane potential generally in the range of –40 to –90 mV. Changes in potential are due to movement of ions. 14 Recap 15 Establishing Membrane Potential a) First, the action of the Na+/K+-ATPase pump sets up the concentration gradients for Na+ and K+ (3 Na+ ions pumped out for every 2 K+ ions pumped in) b) Then there is a greater flux of K+ out of the cell than Na+ into the cell. This is because in a resting membrane there are a greater number of open K+ channels than there are Na+ channels (greater permeability to K+ than there is to Na+). Because there is greater net efflux than influx of positive ions during this step, a significant negative membrane potential develops. 16 Establishing Membrane Potential c) In the steady-state, the flux of ions across the membrane reaches a dynamic balance. Because the membrane potential is not equal to the equilibrium potential for either ion, there is a small but steady leak of Na+ into the cell and K+ out of the cell. 17 Recap Terminology When talking about action potentials and graded potentials we use these terms: depolarization, repolarization, hyperpolarization. These terms are all relative to the resting membrane potential (RMP). Depolarization is the potential moving from RMP to less negative values. Repolarization is the potential moving back to the RMP. Hyperpolarization is the potential moving away from the RMP in a more negative direction. 18 Recap 19 Graded Potentials Graded potentials are changes in membrane potential that are confined to a relatively small region of the plasma membrane. They are called graded potentials simply because the magnitude of the potential change can vary (is “graded”). Graded potentials are given various names related to the location of the potential or the function they perform; for instance, receptor potential, synaptic potential, and pacemaker potential. 20 Graded Potentials 21 Action Potentials Action potentials are generally very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second. The ability to generate action potentials is known as excitability. This ability is possessed by neurons, muscle cells and some other types of cells. An action potential is a large change in membrane potential and is an “all or none” response. 22 Action Potential Membrane Depolarization In order to cause an action potential, a cell must utilize several types of ion channels. Ligand-gated channels and mechanically gated channels often serve as the initial stimulus for an action potential. Voltage-gated channels give a membrane the ability to undergo action potentials by allowing the rapid depolarization and repolarization phases of the response. There are dozens of different types of voltage-gated ion channels, varying by which ion they conduct (e.g., Na+, K+, Ca2+, or Cl-) and in how they behave as the membrane voltage changes. 23 Voltage-Gated Na+& K+ Channels Depolarization causes Na+ channels to rapidly open, then undergo inactivation followed by the opening of K+ channels. When the membrane repolarizes to negative voltages, both channels return to the closed state. 24 Mechanism of an Action Potential 25 Control Mechanisms of an Action Potential 26 Synapses 27 Synapses Synapses are junctions between two neurons. They can be chemical or electrical. In an electrical synapse, the electrical activity of the presynapticneuron affects the electrical activity of the postsynaptic neuron. Chemical synapses utilize neurotransmitters. 28 Functional Anatomy of Synapses Electrical ◦ Pre- and post-synaptic cells are connected by gap junctions. Chemical ◦ Pre-synaptic neurons release neurotransmitter from their axon terminals. ◦ Neurotransmitter binds to receptors on post-synaptic neurons. 29 Anatomy of a Chemical Synapse 30 Mechanisms of Neurotransmitter Release 31 Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in presentation mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Slide Show mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 32 Docking of Vesicles and Release of Neurotransmitters Neurotransmitters are produced and stored in vesicles at the axon terminal. When the cell is stimulated, the intracellular Ca2+ levels increase and stimulate the vesicles to translocate and bind to the plasma membrane via the SNARE proteins. The neurotransmitter is then released via exocytosis. 33 Removal of Neurotransmitter To terminate the signal in a chemical synapse the neurotransmitter must be removed. This is accomplished by: 1. Diffusion of the transmitter from the cleft 2. Degradation of the transmitter by enzymes 3. Reuptake into the pre-synaptic cells for reuse 34 Modification of Synaptic Transmission by Drugs and Disease Drugs act by interfering with or stimulating normal processes in the neuron involved in neurotransmitter synthesis, storage, and release, and in receptor activation. Low doses of botulinum toxin (Botox) are injected therapeutically to treat a number of conditions, including facial wrinkles, severe sweating, uncontrollable blinking, misalignment of the eyes, and others. 35 36 Neuromodulators Neuromodulators modify both the presynaptic and the postsynaptic cell’s response to specific neurotransmitters, amplifying or dampening the effectiveness of ongoing synaptic activity. Receptors for neurotransmitters affect ion channels that directly affect excitation or inhibition of the postsynaptic cell, and these mechanisms operate within milliseconds. Receptors for neuromodulators bring about changes in metabolic processes in neurons, and these changes can occur over minutes, hours, or even days, include alterations in enzyme activity or, through influences on DNA transcription, in protein synthesis. Thus, neurotransmitters are involved in rapid communication, whereas neuromodulators tend to be associated with slower events such as learning, development, motivational states, and some types of sensory or motor activities. 37 Alzheimer’s Disease Neurons associated with the ACh system degenerate in people with Alzheimer’s disease. Alzheimer’s disease affects 10 to 15 percent of people over age 65, and 50 percent of people over age 85. Because of the degeneration of cholinergic neurons, this disease is associated with a decreased amount of ACh in certain areas of the brain and even the loss of the postsynaptic neurons that would have responded to it. These defects and those in other neurotransmitter systems that are affected in this disease are related to the declining language and perceptual abilities, confusion, and memory loss that characterize Alzheimer’s victims. 38 Biogenic Amines Biogenic amine neurotransmitters are made from amino acids as follows: Catecholamines Made from tyrosine: Dopamine Norepinephrine Epinephrine Made from tryptophan: Serotonin Made from histidine: Histamine The enzymes which degrade the biogenic amine neurotransmitters are: Monoamine oxidase (MAO) Catechol-o-methyltransferase 39 Synthesis of Catecholamines 40 Adrenergic Receptors Adrenergic receptors are utilized by the neurotransmitters Norepinphrine (NE) and Epinephrine (Epi). NE is found in both the CNS and PNS but Epi is found mainly in the PNS. Adrenergic comes from historical use as Noradrenaline (NA) and adrenaline for NE and Epi, respectively. Adrenergic receptors are G protein coupledand generally are linked to second messenger signal transduction pathways. Alpha (α) adrenergic receptors ‒ Alpha1 ‒ Alpha2 Beta (β) adrenergic receptors ‒ Beta1 ‒ Beta2 ‒ Beta3 41 Parkinson’s Disease This disease involves the loss of dopamine-releasing neurons in the substantia nigra (area in the brain where dopamine is produced). Symptoms include persistent tremors, head nodding and pill rolling behaviors, a forward bent walking posture, shuffling gait, stiff facial expressions and they are slow in initiating and executing movement. The cause is not clearly understood, but loss of the dopamine neurons is critical. It is currently treated with the drug L-Dopa in the initial stages to alleviate symptoms. This is often given with the drug deprenyl (which prevents the breakdown of L-Dopa). This is NOT curative. These drugs only treat the symptoms. Experimental treatments currently include deep brain stimulation by surgically implanting electrodes, gene therapy and fetal/stem cell transplants. 42 Serotonin Also known as 5-hydroxytryptamine or 5-HT CNS neurotransmitter 5-HT is also made by enterochromaffin cells (secretion cells; 90%) in the gut and collected by platelets Main CNS location Brainstem (1-2%) Drugs Selective serotonin reuptake inhibitors (SSRI) are used for depression. LSD stimulates a subtype serotonin receptor. Functions Regulating sleep Emotions Excessive serotonin release by gut increases motility, causing diarrhea Regulates cell growth Vascular smooth muscle cell contraction 43 Histamine CNS neurotransmitter whose major location is the hypothalamus Histamine is commonly known for paracrine actions. Histamine is also found in the peripheral system. It is involved in allergic reactions, nerve sensitization, and acid production in the stomach. 44 Structure of the Nervous System 45 Central Nervous System: Brain [Commissural fibers uniting the cerebral hemispheres] 46 Frontal lobe. The largest lobe of the brain, located in the front of the head, the frontal lobe is involved in personality characteristics, decision-making and movement. Recognition of smell usually involves parts of the frontal lobe. The frontal lobe contains Broca’s area, which is associated with speech ability. Parietal lobe. The middle part of the brain, the parietal lobe helps a person identify objects and understand spatial relationships (where one’s body is compared with objects around the person). The parietal lobe is also involved in interpreting pain and touch in the body. The parietal lobe houses Wernicke’s area, which helps the brain understand spoken language. Occipital lobe. The occipital lobe is the back part of the brain that is involved with vision. Temporal lobe. The sides of the brain, temporal lobes are involved in short-term memory, speech, musical rhythm and some degree of smell recognition. 47 Aphasia vs Apraxia Aphasia ◦ a language disorder characterized by difficulties with speaking, understanding written or spoken language, reading, and writing ◦ E.g. impairment of Wernicke’s area (comprehension) Apraxia ◦ a speech disorder that affects the physical coordination needed for speaking. ◦ Unlike aphasia, apraxia does not affect people's ability to understand language. ◦ E.g. impairment of Broca’s area (motor) 48 Forebrain The cerebrum consists of the right and left cerebral hemispheres as well as certain other structures on the underside of the brain. The central core of the forebrain is formed by the diencephalon. 49 Forebrain The cerebral hemispheres consist of the cerebral cortex, an outer shell of gray matter composed primarily of cell bodies that give the area a gray appearance, and an inner layer of white matter, composed primarily of myelinated fiber tracts. This overlies cell clusters, which are also gray matter and are collectively termed the subcortical nuclei. The fiber tracts consist of the many nerve fibers that bring information into the cerebrum, carry information out, and connect different areas within a hemisphere. 50 The cortex layers of the left and right cerebral hemispheres, although largely separated by a deep longitudinal division, are connected by a massive bundle of nerve fibers known as the corpus callosum. Frontal The cortex of each cerebral hemisphere is divided into four lobes: Parietal Occipital Temporal. Forebrain: Cerebral Cortex The cortex is 3 mm in thickness but is highly folded. This results in an area containing cortical neurons that is four times larger than it would be if unfolded, without appreciably increasing the volume of the brain. 51 Forebrain: Cerebral Cortex This folding results in the characteristic external appearance of the human cerebrum, with its sinuous ridges called gyri (singular, gyrus) separated by grooves called sulci (singular, sulcus). The cells of the human cerebral cortex are organized in six distinct layers, composed of two basic types: pyramidal cells (named for the shape of their cell bodies) and nonpyramidal cells. The pyramidal cells form the major output cells of the cortex, sending their axons to other parts of the cortex and to other parts of the central nervous system. Nonpyramidal cells are mostly involved in receiving inputs into the cortex and in local processing of information. 52 Forebrain: Cerebral Cortex The cerebral cortex is the integrating area of the nervous system. In the cerebral cortex, basic afferent information is collected and processed into meaningful perceptual images, and control over the systems that govern the movement of the skeletal muscles is refined. The subcortical nuclei are heterogeneous groups of gray matter that lie deep within the cerebral hemispheres. Predominant among them are the basal nuclei (also known as basal ganglia), which play an important role in controlling movement and posture and in more complex aspects of behavior. 53 Forebrain: Diencephalon The diencephalon, which is divided in two by the narrow third cerebral ventricle, contains the thalamus, hypothalamus, and epithalamus. The thalamus is a collection of several large nuclei that serve as synaptic relay stations and important integrating centers for most inputs to the cortex, and plays a key role general arousal. The thalamus also is involved in focusing attention. For example, it is responsible for filtering out extraneous sensory information. 54 Forebrain: Diencephalon The hypothalamus lies below the thalamus and is on the undersurface of the brain and it contains different cell groups and pathways that form the master command center for neural and endocrine coordination. Behaviors having to do with preservation of the individual (for example, eating and drinking) and preservation of the species (reproduction) are among the many functions of the hypothalamus. The hypothalamus lies directly above and is connected by a stalk to pituitary gland, an important endocrine structure that the hypothalamus regulates. 55 Forebrain: Diencephalon The epithalamus is a small mass of tissue that includes the pineal gland, which has a role in regulating biological rhythms. Some of the forebrain areas, consisting of both gray and white matter, are also classified together in a functional system called the limbic system. Structures within the limbic system are associated with learning, emotional experience and behavior, and a wide variety of visceral and endocrine functions. 56 Limbic System 57 Cerebellum Although the cerebellum does not initiate voluntary movements, it is an important center for coordinating movements and for controlling posture and balance. To carry out these functions, the cerebellum receives information from the muscles and joints, skin, eyes and ears, viscera, and the parts of the brain involved in control of movement. Although the cerebellum’s function is almost exclusively motor, it is implicated in some forms of learning. 58 Brainstem All the nerve fibers that relay signals between the forebrain, cerebellum, and spinal cord pass through the brainstem. Running through the core of the brainstem and consisting of loosely arranged neuron cell bodies intermingled with bundles of axons, is the reticular formation, the one part of the brain absolutely essential for life. It receives and integrates input from all regions of the central nervous system and processes a great deal of neural information. The reticular formation is involved in motor functions, cardiovascular and respiratory control, and the mechanisms that regulate sleep and wakefulness and focus of attention. 59 Brainstem Some reticular formation neurons are clustered together, forming brainstem nuclei and integrating centers. These include the cardiovascular, respiratory, swallowing, and vomiting centers, all of which will be discussed in later chapters. The reticular formation also has nuclei important in eyemovement control and the reflex orientation of the body in space. The brainstem contains nuclei involved in processing information for 10 of the 12 pairs of cranial nerves. These are the peripheral nerves that connect directly with the brain and innervate the muscles, glands, and sensory receptors of the head, as well as many organs in the thoracic and abdominal cavities. 60 Cranial Nerves 61 Spinal Cord The spinal cord lies within the bony vertebral column and is a slender cylinder of soft tissue about as big around as the little finger. The central butterfly-shaped area of gray matter is composed of interneurons, the cell bodies and dendrites of efferent neurons, the entering axons of afferent neurons, and glial cells. The regions of gray matter projecting toward the back of the body are called the dorsal horns, whereas those oriented toward the front are the ventral horns. The gray matter is surrounded by white matter, which consists of groups of myelinated axons. 62 Spinal Cord These groups of fiber tracts run longitudinally through the cord, some descending to relay information from the brain to the spinal cord, others ascending to transmit information to the brain. Pathways also transmit information between different levels of the spinal cord. Groups of afferent fibers that enter the spinal cord from the peripheral nerves enter on the dorsal side of the cord via the dorsal roots. Small bumps on the dorsal roots, the dorsal root ganglia, contain the cell bodies of these afferent neurons. The axons of efferent neurons leave the spinal cord on the ventral side via the ventral roots. A short distance from the cord, the dorsal and ventral roots from the same level combine to form a spinal nerve, one on each side of the spinal cord. 63 Central Nervous System: Spinal Cord 64 Peripheral Nervous System Neurons in the peripheral nervous system transmit signals between the central nervous system and receptors and effectors in all other parts of the body. The peripheral nervous system has 43 pairs of nerves: 12 pairs of cranial nerves and 31 pairs that connect with the spinal cord as the spinal nerves. The 31 pairs of spinal nerves are designated by the vertebral levels from which they exit: cervical (8), thoracic (12), lumbar (5), sacral (5), and coccygeal (1). 65 Peripheral Nervous System The eight pairs of cervical nerves control the muscles and glands and receive sensory input from the neck, shoulders, arms, and hands. The 12 pairs of thoracic nerves are associated with the chest and upper abdomen. The five pairs of lumbar nerves are associated with the lower abdomen, hips, and legs. The five pairs of sacral nerves are associated with the genitals and lower digestive tract. (A single pair of coccygeal nerves associated with the tailbone brings the total to 31 pairs.) 66 Peripheral Nervous System These peripheral nerves can contain nerve fibers that are the axons of efferent neurons, afferent neurons, or both. All the spinal nerves contain both afferent and efferent fibers, whereas some of the cranial nerves contain only afferent fibers or only efferent fibers. Efferent neurons carry signals out from the central nervous system to muscles or glands. The efferent division of the peripheral nervous system is more complicated than the afferent, being subdivided into a somatic nervous system and an autonomic nervous system. 67 Spinal Nerves 68 69 Autonomic Nervous System The gastrointestinal tract has the enteric nervous system, and although often classified as a subdivision of the autonomic efferent nervous system, it also includes sensory neurons and interneurons. Anatomical and physiological differences within the autonomic nervous system are the basis for its further subdivision into sympathetic and parasympathetic divisions. The neurons of the sympathetic and parasympathetic divisions leave the central nervous system at different levels—the sympathetic fibers from the thoracic (chest) and lumbar regions of the spinal cord, and the parasympathetic fibers from the brainstem and the sacral portion of the spinal cord. 70 Autonomic Nervous System Sympathetic division is also called the thoracolumbar division, has short pre-ganglionic and long post-ganglionic synapses. The major neurotransmitters are ACh at the preganglionic synapse and usually NE and Epi at the postganglionic synapse. This is the “Flight or Fight” response system. Parasympathetic is called the craniosacral division, it has long pre-ganglionic and short post-ganglionic synapses. The major neurotransmitter is ACh at both pre- and postganglionic synapses. This is the “Rest and Digest” system. 71 Autonomic Nervous System In addition to the classical autonomic neurotransmitters just described, there is a widespread network of postganglionic neurons recognized as nonadrenergic and noncholinergic. These neurons use nitric oxide and other neurotransmitters to mediate some forms of blood vessel dilation and to regulate various gastrointestinal, respiratory, urinary, and reproductive functions. The great majority of acetylcholine receptors in the autonomic ganglia are nicotinic receptors. In contrast, the acetylcholine receptors on smooth muscle, cardiac muscle, and gland cells are muscarinic receptors. 72 Autonomic Nervous System The cholinergic receptors on skeletal muscle fibers, innervated by the somatic motor neurons, not autonomic neurons, are nicotinic receptors. One set of postganglionic neurons in the sympathetic division never develops axons. Instead, they form the adrenal medulla. Upon activation by preganglionic sympathetic axons, cells of the adrenal medulla release a mixture of about 80 percent epinephrine and 20 percent norepinephrine into the blood (plus small amounts of other substances, including dopamine, ATP, and neuropeptides). 73 Autonomic Nervous System These catecholamines, properly called hormones rather than neurotransmitters in this circumstance, are transported via the blood to effector cells having receptors sensitive to them. The heart and many glands and smooth muscles are innervated by both sympathetic and parasympathetic fibers; that is, they receive dual innervation. Whatever effect one division has on the effector cells, the other division usually has the opposite effect. Moreover, the two divisions are usually activated reciprocally; that is, as the activity of one division increases, the activity of the other decreases. 74 Autonomic nervous system 75 ANS vs SNS 76 Cerebrospinal Fluid 77 Physical Support of the CNS Bone serves to support and to protect the structures of the CNS and PNS. Cranium Vertebrae Meninges are the membranes that line the structures and add additional support and protection. Dura mater Arachnoid mater Pia mater Cerebrospinal fluid (CSF) protects and cushions the structures. 78 The Meninges There are three layers of the meninges. From external to internal they are: dura mater, arachnoid mater, and pia mater. The job of the meninges is to: 1. Cover and protect the CNS 2. Protect blood vessels and enclose the venous sinuses 3. Contain cerebrospinal fluid 4. Form partitions in the skull 79 The Meninges The subarachnoid space is filled with CSF and contains the largest blood vessels serving the brain. In the superior sagittal sinus the arachnoid villi absorb the CSF into the venous blood system. The pia mater clings to the brain and contains a network of blood vessels. Meningitis is an inflammation of the meninges and is a serious threat to the brain since bacterial or viral meningitis can spread to the CNS. If the brain itself is inflamed it is called encephalitis. Meningitis is usually diagnosed by examining the CSF obtained via a lumbar puncture for microbes or viruses. 80 Cerebrospinal Fluid (CSF) CSF is the extracellular fluid of the CNS and it is secreted by ependymal cells of the choroid plexus. It circulates through the subarachnoid space and ventricles and is reabsorbed by arachnoid villi. Total volume of CSF present at any given time is approximately 125–150 mL. The choroid plexus produces 400–500 mL/day, so the entire contents are recycled three times a day. This is important to maintaining a stable and optimal environment. 81 Hydrocephalus Hydrocephalus is “water on the brain”. It is an accumulation of CSF in the brain that is often caused by tumors. In newborns it results in enlargement of the head. In adults (whose skull bones have fused) it puts pressure on the brain and causes brain damage. It is treated by inserting a shunt to drain the fluid. 82 Blood-Brain Barrier This is a protective mechanism that helps maintain a stable environment for the brain. Substances in the brain’s capillaries are separated from the extracellular space by the continuous endothelium of the capillary walls and a thick basal lamina surrounding the capillaries. The “feet” of the astrocytes surrounding the capillaries also contribute. These capillaries are the least permeable ones in the body. This barrier is very selective. Things that are highly lipidsoluble cross easily. 83 Cerebrovascular Accidents Otherwise known as a stroke, CAs can be caused by a decreased blood supply or a hemorrhage. An ischemic stroke is one caused by the occlusion of cerebral arteries, usually by a blood clot that blocks an artery or by the rupture of an atherosclerotic plaque. If it is detected early enough, “clot busting” drugs (TPA-tissue plasminogen activator) can be administered. This dissolves the clot and restores blood flow to the area. A hemorrhagic stroke is one where the blood vessel has ruptured. The best treatment available is to try to cauterize the vessel (if possible) and to alleviate the pressure on the brain caused by the bleeding. 84 Head Injuries Head injuries are the leading cause of accidental death in North America. Hard blows to the head result in a coup injury (the site of the blow) as well as a contrecoup (where the brain hits the other side of the skull). A concussion is an alteration of brain function following a blow to the head. This is usually temporary and the victim can show signs of dizziness, or may lose consciousness. Multiple concussions can cause cumulative damage (boxers and football player have to be carefully monitored for this). A contusion is bruising of the brain. This always causes some permanent damage. If it occurs in the brainstem it can cause coma or death. Head blows may also result in subdural or subarachnoid hemorrhages which can cause permanent neurological damage and death. Cerebral edema can also be caused by a blow to the head. This can cause permanent damage or death by putting pressure on the brain. 85