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THE CENTRAL NERVOUS SYSTEM -ANATOMY OF THE BRAIN -NEURONAL FUNCTION -DISEASE OF THE BRAIN 1 Nervous System Central Nervous System Brain Spinal Cord • cell body (soma) • dendrites (input structure) • Peripheral Nervous System receive inputs from other neurons axon (output structure) a fiber that carries messages from the cell to dendrites of other neurons 2 Functional Classes of Neurons Neuroglia 3 Brain - protection • Protected by: – cranial bones – meninges • pia mater • arachnoid • dura mater – Cerebrospinal fluid Cerebrospinal fluid • Mechanical protection • Chemical protection • Medium for exchange between blood and nervous tissue 4 Brain component Cerebral cortex Cerebral cortex Basal nuclei (lateral to thalamus) Basal nuclei Thalamus (medial) Thalamus Hypothalamus Hypothalamus Cerebellum Cerebellum Midbrain Brain stem Brain stem (midbrain, pons, and medulla) Pons Medulla Spinal cord Major Functions 1. Sensory perception 2. Voluntary control of movement 3. Language 4. Personality traits 5. Sophisticated mental events, such as thinking memory, decision making, creativity, and self-consciousness 1. Inhibition of muscle tone 2. Coordination of slow, sustained movements 3. Suppression of useless patterns of movements 1. Relay station for all synaptic input 2. Crude awareness of sensation 3. Some degree of consciousness 4. Role in motor control 1. Regulation of many homeostatic functions, such as temperature control, thirst, urine output, and food intake 2. Important link between nervous and endocrine systems 3. Extensive involvement with emotion and basic behavioral patterns 1. Maintenance of balance 2. Enhancement of muscle tone 3. Coordination and planning of skilled voluntary muscle activity 1. Origin of majority of peripheral cranial nerves 2. Cardiovascular, respiratory, and digestive control centers 3. Regulation of muscle reflexes involved with equilibrium and posture 4. Reception and integration of all synaptic input from spinal cord; arousal and activation of cerebral cortex 5. Role in sleep-wake cycle Brain component Cerebral cortex Basal nuclei Thalamus Hypothalamus Cerebellum Brain stem (midbrain, pons, and medulla) Table 5-2, p. 141 5 The Brain Stem • Brain stem consists of: – medulla oblongata – pons – midbrain • Brain stem produces automatic behaviours essential for survival • Respiration, heart rate • vomiting The Cerebellum • Approximately 10% of brain mass but contains nearly half of all brain neurons • Coordinates skeletal muscle contraction • Regulates posture and balance 6 The Diencephalon • Thalamus – edits all sensory inputs (except smell) to cerebral cortex – functions in cognition and awareness • allows crude recognition of pain, temp and pressure – relays information from cerebellum to primary motor cortex The Diencephalon • Hypothalamus: – major regulator of homeostasis • Produces hormones • Regulates emotional responses and behaviours related to sexual arousal • Regulates eating and drinking • Controls body temperature • Regulates circadian rhythms and consciousness 7 The Cerebrum • Cerebrum - outer part of brain consisting of – Cortex • allows ‘consciousness’ Motor cortex Somatosensory cortex Sensory associative cortex Pars opercularis Visual associative cortex Brocaʼs area Visual cortex Primary Auditory cortex Wernickeʼs area 8 Foot Action Hand Action Mouth Action Electroencephalogram (EEG) • Record of postsynaptic activity in cortical neurons • “Brain waves” • Three major uses – Clinical tool in diagnosis of cerebral dysfunction – Used in legal determination of brain death – Used to distinguish various stages of sleep 9 Electroencephalogram (EEG) 10 EPILESPY •Localised electrical discharge •Involuntary muscle contraction •Abnormal sensory experiences •Frequent •Synchronous discharge throughout seizure Spinal Cord • Extends from brain stem through vertebral canal • 31 pairs of spinal nerves emerge from spinal cord through spaces formed between arches of adjacent vertebrae – Named for region of vertebral column from which they emerge • • • • • 8 pairs cervical (neck) nerves 12 pairs thoracic (chest) nerves 5 pairs lumbar (abdominal) nerves 5 pairs sacral (pelvic) nerves 1 pair coccygeal (tailbone) nerves 11 Spinal Nerves The spinal cord • Spinal cord protected by: – vertebrae – meninges • pia mater • arachnoid • dura mater – cerebrospinal fluid 12 Spinal reflexes • Spinal cord acts as integrating centre for spinal reflexes – Reflex - rapid, predictable, involuntary sequence of actions that occur in response to a particular stimulus. Components of a reflex arc Reflex arc has five components: – receptor – sensory neuron – integration centre – motor neuron – Effector • Somatic reflex – skeletal muscle • Autonomic reflex – smooth muscle, cardiac muscle or gland Pain, temperature, pH, changes in internal environment 13 Types of Receptors • Photoreceptors – Responsive to visible wavelengths of light • Mechanoreceptors – Sensitive to mechanical energy • Thermoreceptors – Sensitive to heat and cold • Osmoreceptors – Detect changes in concentration of solutes in body fluids and resultant changes in osmotic activity • Chemoreceptors – Sensitive to specific chemicals – Include receptors for smell and taste and receptors that detect O2 and CO2 concentrations in blood and chemical content of digestive tract • Nociceptors – Pain receptors that are sensitive to tissue damage or distortion of tissue Brain disease 14 The brain is composed of 1011 neurons What you are born with is what you have for life Neurons are dying everyday: at least 0.5% a year after age 50 ALZHEIMER’S DISEASE Estimated that 4,000,000 people in U.S. have Alzheimer's disease. Estimated that 25-35% of people over age 85 have dementia. Caring for patient with Alzheimer's disease can cost $47,000 per year (NIH). 40, 000 patients with AD in Ireland 15 NORMAL PET normal brain AD PET AD brain 16 DEPOSITION OF PLAQUES -senile plaques -amyloid plaques Parkinson’s Disease 17 Normal Parkinson’s Loss of pigmentation in substantia nigra due to loss of dopaminergic neurons 18 Treatment -drugs (L-DOPA) -Deep brain stimulation (neurostimulator) How to neurons function? 19 Neural Communication • Nerve and muscle are excitable tissues • Can undergo rapid changes in their membrane potentials • Can change their resting potentials into electrical signals – Electrical signals are critical to the function of the nervous system and all muscles Nerve cells - neurons. • Approx. 1011 neurons in the brain. Each neuron has about 103 connections 20 The Membrane • The membrane surrounds the neuron. • It is composed of lipid and protein. 21 Ions and the Resting Potential • • Ions are electrically-charged molecules e.g. sodium (Na+), potassium (K+), chloride (Cl-). The resting potential exists because ions are concentrated on different sides of the membrane. – Na+ and Cl- outside the cell. – K+ and organic anions inside the cell. Cl- Na+ Na+ Organic anions (-) K+ Na+ Na+ Cl- outside inside K+ Organic anions (-) Organic anions (-) The Resting Potential • There is an electrical charge across the membrane. • This is the membrane potential. • The resting potential (when the cell is not firing) is a 70mV difference between the inside and the outside. + outside - inside + - + - - + + - Resting potential of neuron = -70mV 22 Action potentials: Rapid depolarization • When partial depolarization reaches the activation threshold, voltage-gated sodium ion channels open. • Sodium ions rush in. • The membrane potential changes from -70mV to +40mV. Na+ + - Na+ Na+ + Action potentials: Repolarization • Sodium ion channels close and become refractory. • Depolarization triggers opening of voltage-gated potassium ion channels. • K+ ions rush out of the cell, repolarizing and then hyperpolarizing the membrane. Na+ Na+ K+ Na+ K+ K+ + 23 Types of Changes in Membrane Potential Action Potentials Permeability Changes and Ion Fluxes During an Action Potential 24 Neuronal firing: the action potential • The action potential is a rapid depolarization of the membrane. • It starts at the axon hillock and passes quickly along the axon. • The membrane is quickly repolarized to allow subsequent firing. Myelination • Most mammalian axons are myelinated. • The myelin sheath is provided by oligodendrocytes and Schwann cells. • Myelin is insulating, preventing passage of ions over the membrane. 25 Saltatory Conduction • Myelinated regions of axon are electrically insulated. • Electrical charge moves along the axon rather than across the membrane. • Action potentials occur only at unmyelinated regions: nodes of Ranvier. Myelin sheath Node of Ranvier 26 Synapses • Junction between two neurons • Primary means by which one neuron directly interacts with another neuron • Anatomy of a synapse – Presynaptic neuron – conducts action potential toward synapse – Synaptic knob – contains synaptic vesicles – Synaptic vesicles – stores neurotransmitter (carries signal across a synapse) – Postsynaptic neuron – neuron whose action potentials are propagated away from the synapse – Synaptic cleft – space between the presynaptic and postsynaptic neurons Synapse 27 Neurotransmitters • Vary from synapse to synapse • Same neurotransmitter is always released at a particular synapse • Quickly removed from the synaptic cleft • Some common neurotransmitters – – – – – – – – – – Acetylcholine Dopamine Norepinephrine Epinephrine Serotonin Histamine Glycine Glutamate Aspartate Gamma-aminobutyric acid (GABA) Three Nobel Prize Winners on Synaptic Transmission Arvid Carlsson discovered dopamine is a neurotransmitter. Carlsson also found lack of dopamine in the brain of Parkinson patients. Paul Greengard studied in detail how neurotransmitters carry out their work in the neurons. Dopamine activated a certain protein (DARPP-32), which could change the function of many other proteins. Eric Kandel proved that learning and memory processes involve a change of form and function of the synapse, increasing its efficiency. This research was on a certain kind of snail, the Sea Slug (Aplysia). With its relatively low number of 20,000 neurons, this snail is suitable for neuron research. 28 • Additional slides (not shown in lecture) Synapse axon of presynaptic neuron dendrite of postsynaptic neuron 29 Synaptic transmission • Information is transmitted from the presynaptic neuron to the postsynaptic cell. • Chemical neurotransmitters cross the synapse, from the terminal to the dendrite or soma. • The synapse is very narrow, so transmission is fast. • a synapse can be excitatory or inhibitory • arrival of activity at an excitatory synapse depolarizes the local membrane potential of the postsynaptic cell and makes the cell more prone to firing • arrival of activity at an inhibitory synapse hyperpolarizes the local membrane potential of the postsynaptic cell and makes it less prone to firing • the greater the synaptic strength, the greater the depolarization or hyperpolarization 30 Neural Communication • Membrane electrical states – Polarization • Any state when the membrane potential is other than 0mV – Depolarization • Membrane becomes less polarized than at resting potential – Repolarization • Membrane returns to resting potential after having been depolarized – Hyperpolarization • Membrane becomes more polarized than at resting potential Action Potentials 31 Neuron • Once initiated, action potentials are conducted throughout a nerve fiber • Action potentials are propagated from the axon hillock to the axon terminals • Basic parts of neuron (nerve cell) – Cell body – Dendrites – Axon Neuron • Cell body – Houses the nucleus and organelles • Dendrites – Project from cell body and increase surface area available for receiving signals from other nerve cells – Signal toward the cell body Dendrite and cell body serve as the neurons input zone. 32 Saltatory Conduction 33 Neural communication Neurons transport information via electrical action potentials. At the synapse the transmission is mediated by chemical macromolecules (neurotransmitter proteins). 34