The Nervous System

1. The Nervous System Emily Armstrong, Jennifer LeBeau, Olivia Ondeck

2. Overview • Human nervous system – most complex computer in the world • Made up of Nerve Cells – Neurons • About 100 billion in the human brain • Connections analyzed with fMRI

3. Evolution • Began with chemotaxis in early prokaryotes (billions of years ago) • Finding food • Directing motion • Multicellular organisms – need to communicate internally • By Cambrian Explosion (500 million years +) – modern animal nervous systems

4. Organization (Simple to Complex) • Nerve Nets – loose, widespread net of neurons • Cnidarians (Hydra) • Nerves – neurons bundled up into fibers • Echinoderm (Starfish)

5. Organization (cont.) • Cephalization – anterior cluster • Central Nervous System (CNS) – brain, longitudinal chords (simplest in flatworms) • Ganglia – segmental clusters of neurons • Peripheral Nervous System (PNS) – connects CNS to the rest of the body • Complexity is determined by lifestyle • Molluscs: clams vs. squids

6. Information Processing Reflex – simplest circuits, automatic in the body

7. Neurons • Cell body – contains organelles, nucleus • Dendrites – branches, receive signals • Axon – longer extension, transmits signals • Axon Hillock – conical section, signals generated here • Myelin Sheath – enclose axon to protect signal • Synapse – point of communication to another cell

8. Glia • Supporting Cells for Neurons • Often outnumber neurons, especially in mammals • Astrocytes– structural support in CNS; regulate extracellular fluid; create blood-brain barrier; dilate blood vessels; facilitate transmission (learning) • Radial Glia – make tracks for neurons in embryo; can be stem cells • Oligodendrocytes (CNS) and Schwann Cells (PNS) – form the myelin sheath, electrically isolate with lipids; Multiple Sclerosis

9. Membrane Potential • Electrical difference (Voltage) across the membrane • Resting Potential – when neuron is not transmitting • -60 to -80 mV in neurons • Cell is negative to environment • Equilibrium Potential (Eion) – occurs when the electrical gradient and chemical gradient are in balance • K+ and Na+ flow constantly, balancing each other

10. Membrane Potential (cont.) • Nerst Equation (at 37°C, net charge +1): • Eion= 62 mV [log ion(outside) / ion(inside)] • Determines potential at Equilibrium Potential (E) Cytosol Extracellular Fluid Na+ (15 mM) K+ (150 mM) Cl- (10 mM) A- (100 mM) - - - - - - + + + + + + + Na+ (150 mM) K+ (5 mM) Cl- (120 mM)

11. Membrane Potential (cont.) • Different Types of Channels • Ungated– always open (Na+ and K+) • Gated – opened by stimuli • Stretch-gated: open when membrane physically changed • Ligand-gated: in synapses; open when bound to by certain chemicals (neurotransmitters) • Voltage-gated: when membrane potential changes; in axon and dendrites

12. Action Potential • Membrane potential can be changed by stimuli • Hyperpolarization: increase in membrane potential (K+ open) • Depolarization: reduction in membrane potential (Na+ open) • Graded Potentials: amount of change depends on strength of stimulus • Approach -92 mV and +62 mV • Polarization is minor until it reaches the threshold and becomes an action potential

13. Action Potential (cont.) • When action potential is triggered, a signal is transmitted, sometimes over long distances • Action potentials last 1-2 milliseconds • Can be sent quickly and repeatedly • Travels like a wave down the axon • Depolarized area (Na+ influx) rolls down the axon • Followed by repolarization area (K+ efflux) • Forces action potential to travel one direction

14. Steps to Action Potentials • Resting: all activation gates closed; potential constant • Depolarization: Na+ gates open, influx into axon • Risingphase: inside of axon becomes positive • Fallingphase: Na+ gates close, K+ gates open and efflux; negative again • Undershoot: K+ gates remain open for a short time before balance is restored

15. Action Potential Conduction • Speed is important in many reflexes and reactions • Wider axon = faster conduction • Example: more water flows through a wider hose • Role of the myelin sheath • Extracellular fluid only has contact with axon at Nodes of Ranvier • Saltatory Conduction – action potential “jumps” between nodes, very fast

16. Synapses – Neuron Communication • Neurons communicate in two ways • Electrical Synapses – gap junctions that allow current from action potential to pass; involved in reflexes • Chemical Synapses – release chemical signals • Far more common type of signaling

17. Chemical Synapses • Synaptic Vesicles – contain neurotransmitter • Action potential causes exocytosis • Neurotransmitter binds to receptors on postsynaptic cell • Ligand-gated ion channels open and change potential of receiving cell

18. Direct Synaptic Transmission • Ions cross ligand-gated channels into postsynaptic cell • Postsynaptic Potential • Excitatory Postsynaptic Potentials (EPSP) – depolarize • Inhibitory Postsynaptic Potentials (IPSP) – hyperpolarize • Often one EPSP is not enough to reach threshold • Temporal Summation – two EPSPs close together, potentials add together • Spatial Summation – two synapses deliver signals at the same time • Can counteract or add to each other

19. Indirect Synaptic Transmission • Neurotransmitter binds to receptor, doesn’t open a channel • Starts a signal transduction pathway with second messenger • Cyclic AMP (cAMP cycles) • Norepinephrine binds to a receptor • cAMP is produced • Many channels can be opened by one neurotransmitter molecule

20. Neurotransmitters • Each binds to its own set group of receptors (sometimes different results) • Acetylcholine – very common in most animals; can inhibit or excite; transfers EPSPs to muscle cells; receptors are used by nicotine to slow heart contractions • Biogenic Amines – derived from amino acids; often indirect transmission; sometimes function as hormones • Epinephrine: sometimes a hormone • Norepinephrine: involved in depression • Dopamine and Serotonin: affect sleep, mood, attention, learning; receptors used by LSD; deficiency can cause depression

21. Neurotransmitters (cont.) • Amino Acids and Peptides • Amino Acids – gamma aminobutyric acid (GABA), glycine, glutamate, and aspartate • GABA – very inhibitory • Neuropeptides – small amino acid chains; often modified from larger proteins, used with other transmitters • Substance P – excitatory, causes pain perception • Endorphins – decreases pain perception; similar to morphine or heroin; connection to endocrine system • Gases – NO and CO • Synthesized quickly when needed; absorbed by other cells, which make a change and then dissolve • Involved in smooth muscle contractions and erections

22. Vertebrate Organization • Cephalization – separate CNS and PNS • CNS – spinal chord and brain • Cerebrospinal fluid: filtered blood (drains in veins), in central canal of spinal chord and ventricles of brain • White Matter (myelinated axons) vs. Gray Matter (dendrites, cell bodies, unmyelinated)

23. Vertebrate PNS Somatic Nervous System Autonomic Nervous System Deals with internal factors Involuntary Three divisions Sympathetic Parasympathetic Enteric • Deals with external stimuli • Voluntary • Skeletal muscles

24. Autonomic Nervous System • Enteric • Neurons in digestive tract, gallbladder, pancreas • Secretions and peristalsis Sympathetic • “Fight or Flight” • Heart rate increases • Glycogen glucose • Bronchi dilate • Digestion inhibited • Epinephrine (adrenaline) Parasympathetic • “Rest and Digest” • Decreases heart rate • Promotes glycogen • Enhances digestion

25. Brain Development

26. The Brainstem (Lower Brain) • Medulla Oblongata, Pons, Midbrain • Functions: Homeostasis, movement coordination, conducting information • Medulla and Pons – visceral functions (breathing, blood vessels, swallowing, vomiting, digestion) • All information in and out of the brain passes here • Axons cross in the Medulla (Right brain Left side) • Role in walking, large movements • Inferior and Superior Colliculi– auditory and visual reflexes

27. Arousal and Sleep • State of awareness to surroundings • Controlled (in part) by Brainstem • Reticular Formation / Reticular Activating System (RAS) • Selects information that goes to cerebral cortex • More information = greater awakeness • Sleep Centers in the Pons and Medulla • Serotonin – cyclic, causes sleep • Milk contains amino acid precursor • Sleep could help with learning and memory

28. Cerebellum • Coordination, Error Checking of motor, perceptual, cognitive functions • Cognitive Functions – learning, decisions, consciousness, sensory awareness • Major “muscle memory” • Riding Bicycle, Hand-Eye Coordination

29. Diencephalon – “thalamuses” • Epithalamus– pineal gland and choroid plexus (produces spinal fluid from blood) • Thalamus – the “post office” of the brain • All sensory input – distribute to correct cerebral center • Motor output from cerebrum • Hypothalamus - homeostatis • Pituitary hormones • Survival mechanisms • Hunger, thirst, temperature, fight-or-flight • Pleasure and rage (“Pure” behaviors) • Mating behaviors

30. Circadian Rhythms • Biological Clocks • Monitor daily cycles • Sleep, Hunger, Sensitivity • Controlled by structures in the hypothalamus • Suprachiasmatic Nuclei (SCN) • Regulated by External Stimuli • Human clock = 24 hours and 11 minutes

31. Cerebrum • Split into left and right hemispheres • Basal Nuclei • cell clusters in white matter, control learning motion sequences and planning • Cerebral Cortex – outer part of cortex (gray matter) • Largest, most complex part of brain • Highly evolved in mammals • Sensory analysis, motor commands, language • Neocortex– thin, convoluted layer on brain surface • Corpus Callosum – communication between halves

32. Cerebral Cortex • Each Cortex has four lobes with functional areas • Primary Sensory Areas – process specific sensory input • Association Areas – integrate information • Account for mammalian neocortexsize, more complex thought possible

33. Cortex Information Processing • Somatosensory: pressure, pain, position, touch • After integrating, potential can be created at primary motor cortex • Action potentials triggered; motor neurons stimulate a response • Unequal amount of motor cortex devoted to different parts of the body

34. Cortex Lateralization • Competing functions separate during development • Left – logic, math, language, serial process • Fine details and motor control • Timed tasks • Right – patterns, facial recognition, spatial relations, nonverbal thinking, emotions, multi-tasking • Music, reconizing tone • Context of image/situation • “Split-Brain” – way to control seizures; no hemisphere cooperation

35. Language and Speech • Hearing, seeing, generating, and speaking words all occur in different areas of the brain • Tumors, strokes, injury can affect parts of speech • Broca’s Area: part of primary motor cortex controlling face • Understand, but not speak • Wernicke’s Area: portion of temporal lobe • Speak, but not understand

36. Emotions • Complex interactions in the brain • Limbic System – amygdala, hippocampus, olfactory bulb, sections of thalamus and hypothalamus • Mediate emotions • Cause primary responses (laughing, crying) • Essential to bonding with others • Separates mammals from amphibians, reptiles • Attaches feelings to survival functions • Parental care

37. Emotions (cont.) • Emotional memory is separate from event recall • Develops earlier, in separate brain section • Can have an emotional response without clear memory (damaged hippocampus) • Damage to any part of limbic system will change behavior, regulation of emotion, planning, motivation • Lobotomy – disconnects prefrontal cortex from limbic system; treated severe emotional disorders

38. Memory and Learning • Two kinds of memory • Short-term memory: instantaneous memory • Stored in the hippocampus • If hippocampus damaged, no new memories formed • Long-term: “relevant”, accessed repeatedly • More permanent connections in cerebral cortex • Transfer to long-term is easier if associated with previous memory

39. Memory and Learning (cont.) • Learning motor skills • Change in neuron connections over time • Habits of motion are difficult to break • Accent, gait, gestures (very individual) • Rote Memorization • Change in neuron connections • Similar to muscle memory

40. Cellular Learning • Long-Term Potentiation (LTP) – increases strength and efficiency of a neuron connection • Involves a series of fast action potentials • Can last for days or weeks • Fundamental process of learning • Creation of an LTP • Neurotransmitter Glutamate released • Binds to AMPA receptors and NMDA receptors • AMPA – ligand-gated channels, depolarizes • NMDA – only occurs if membrane depolarized (AMPA triggered)

41. Consciousness • Often considered part of philosophy or religion • New imaging techniques (fMRI) • Given the opportunity to examine brain and various levels of consciousness • No “consciousness center” • Consciousness is an emergent property • “Scanning Mechanism” theory – integrates all areas of brain activity into a conscious moment • Still a very new area of research

42. Injuries and Diseases • Mammalian CNS cannot repair itself • Can form new connections to compensate • Stroke Victims • Damage to brain or spinal chord can be devastating • Current research focuses on: • Nerve Cell Development • Neural Stem Cells

43. Nerve Cell Development • Creating connections to right target cells in development • Axon Growth: • Growth Cone – end of elongating axon • Cells around growth cone bind to receptors • Signal axon to grow towards or away • Growth factor from astrocytes, neuron proteins trigger growth • Very similar in nematodes, humans, etc (evolutionary link) • Hopefully will be useful in healing someday

44. Neural Stem Cells • In 1998, it was discovered that neurons are created in adulthood (Dr. Fred Gage) • More produced in active, stimulated individuals • Must come from stem cells • Research difficult because of ethical dilemma over embryonic stem cells • Culture of neural progenitor cells (2001) • Stem cells for either glia or neurons • Hopefully can be used in damage repair

45. Nervous System Disorders • Changing of attitude toward such diseases • More understanding • Treatment instead of institutionalization • Schizophrenia • about 1% of the world • Symptoms • psychotic episodes and a distorted view of reality • delusions, hallucinations (like "hearing voices"), paranoia • Causes • may affect dopamine pathways • increased amounts cause schizophrenic symptoms, and medications block receptors • may also alter glutamate signaling • Drug PCP blocks glutamate receptors and induces strong schizophrenic symptoms • Medications becoming more advanced and safer to use

46. Nervous System Disorders (cont.) • Depression - depressed mood, abnormalities in sleep, appetite, energy level • Major Depressive Disorder • long periods of depression - no interest or enjoyment • affects twice as many women as men • Bipolar Disorder • swings of mood from high to low (two versions of both extremes) • manic phase: delusions of grandeur, risk taking, high self esteem • depression phase: loss of motivation and feelings of worthlessness • Therapy is effective and medicines include Prozac, lithium, and anticonvulsant drugs

47. Nervous System Disorders (cont.) • Alzheimer’s Disease • Mental Deterioration - confusion, memory loss, variety of other symptoms • Beta Amyloid accumulates outside of the neurons, forms plaques • Successful treatment may depend on the early detection; a chemical called Pittsburgh Compound- B (PIB) helps in treatment • Parkinson’s Disease • Motor disorder caused by the death of dopamine secreting neurons on the substantial nigra • Risk increases with advancing age • No cure but brain surgery, deep brain stimulation, and drugs like L-dopa used to manage the symptoms • Embryonic stem cells can be genetically changed and help patients

48. Relation to Other Systems • Nervous System regulates other systems • Digestive – glycogen storage regulated, peristalsis • Circulatory – Heartbeat, cerebrospinal fluid • Endocrine – Stimulates production of hormones, which in turn effect neuron function

49. Themes of Biology • Structure and Function • The Neuron – shaped to pass signals • Organization of nervous systems • Evolution • Increasingly complex organization • Neocortex in mammals • Unchanged methods of neuron development • Science, Technology, and Society • Opinions towards nervous disorders • Stem Cell debate

50. Sources (Pictures) • http://www.martinos.org/neurorecovery/ (fMRI) • http://ridge.icu.ac.jp/biobk/BioBookNERV.html (organization) • http://www.clker.com/clipart-neuron.html (neuron) • http://bio1152.nicerweb.com/Locked/media/ch48/axon.html (Conduction) • http://www.tokresource.org/tok_classes/biobiobio/biomenu/nerves_hormones_homeostasis/index.htm (nodes of Ranvier) • http://www.tokresource.org/tok_classes/biobiobio/biomenu/nerves_hormones_homeostasis/index.htm (synapse diagram) • http://footage.shutterstock.com/clip-323641-stock-footage-neuronal-network-activity-in-brain-or-culture-dish.html (synapse) • http://bio1152.nicerweb.com/Locked/media/ch49/nervous.html (CNS man) • http://bio1152.nicerweb.com/Locked/media/ch48/peripheral.html (PNS diagram) • https://ehumanbiofield.wikispaces.com/The+Brain+JM (brainstem) • http://fasdcenter.samhsa.gov/educationTraining/courses/FASDTheCourse/module2/mod2_ct_at_pg1.cfm (Cerebellum) • http://mashable.com/2010/01/13/haiti-red-cross-donations/ (Red Cross) • http://www.telegraph.co.uk/health/healthnews/5207556/Stem-cells-able-to-reverse-symtoms-of-multiple-sclerosis.html (Stem Cells)