1.INTRODUCTION TO NERVOUS SYSTEM DR QAZI MTIAZ RASOOL H. O.D. PHYSIO

What are we doing with our brains at this moment? :

What are we doing with our brains at this moment? Don’t get nervous about NERVOUS SYSTEM 3/27/2011 0

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The student’s brain; Feeling your chair Squirming (moving) , Watching ,Listening, Remembering ,Paying Attention, Sleeping Feeling anxious Feeling hungry What happens when you ask a question? 3/27/2011 1

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MAINTENANCE AND PROTECTION OF THE CNS:

MAINTENANCE AND PROTECTION OF THE CNS Glial Cells: physical and metabolic support Skull and Spinal Column Cerebrospinal fluid Blood-brain barrier Blood supply 3/27/2011 3

Skull and Spinal Column:

Skull and Spinal Column PROVIDE MECHANICAL SUPPORT PROTECTS THE NEURAL AND SUPPORTING TISSUE 3/27/2011 4

CEREBROSPINAL FLUID:

CEREBROSPINAL FLUID SHOCK ABSORBER DENSITY IS THE SAME AS BRAIN 3/27/2011 5

Blood-brain barrier:

Blood-brain barrier LIMITS ACCESS OF BLOOD MATERIALS TO BRAIN TISSUE PROTECTS BRAIN FROM FLUCTUATIONS IN BLOOD LEVELS 3/27/2011 6

Connective Tissues:

Connective Tissues 7 3/27/2011

Organs:

Organs 3/27/2011 8

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INTRODUCTION TO NERVOUS SYSTEM 3/27/2011 9

Primary Tissues:

3/27/2011 10 Primary Tissues

Systems:

Systems 3/27/2011 11

Homeostasis:

Homeostasis Maintaining constancy of internal environment. Body temp ; urine vol ; gas vol ; Circulation, movement 2.Dynamic consistency. Sensory device, sight, hearing, taste, pain Maintained by feedback loops. 3/27/2011 12

Basic physiological Functions of the Nervous System :

Basic physiological Functions of the Nervous System Sensation Monitors changes/events occurring in and outside the body. Such changes are known as stimuli and the cells that monitor them are receptors. Integration The parallel processing and interpretation of sensory information to determine the appropriate response Reaction Motor output. The activation of muscles or glands (typically via the release of neurotransmitters (NTs)) 3/27/2011 13

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. 1. Electrical properties of the neuron 2. Signal transmission 3. Action potential 4. Events at the synapse 5. Electrical synapses 6. Ionic environments of the neurons 7. Chemical messengers of the neurons a. Neurotransmitters b. Neuromodulators c. Neuropeptides d. Neurohormones 3/27/2011 14 Basic Principles of NS Function at molecular level

NUMBER:

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History of Neurobiology:

History of Neurobiology 3/27/2011 16

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Conduits of vital fluids:

Conduits of vital fluids 3/27/2011 18 . Galen (130-200 AD

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Descrates-1650 3/27/2011 19

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3/27/2011 20 Luigi Galvani . (1737-1798 AD)

Cell theory:

Cell theory Schlieden +Schwann-1839 3/27/2011 21

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3/27/2011 22 Camillo Golgi

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Reymonds-1896 3/27/2011 23

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3/27/2011 24 Ramón y Cajal (1852-1934)

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Waldeyer 3/27/2011 25

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A squid and two knights:

A squid and two knights 3/27/2011 28 Sir Andrew Huxley and Sir Alan Hodgkin

Evolution:

Evolution 3/27/2011 29

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3/27/2011 30 Evolution of the Nervous System 3/27/2011 30 Evolution of the Nervous System

Is Handedness Inherited?:

Is Handedness Inherited? human bias for right-handedness has been around a long time and is pervasive studies of prehistoric cave drawings, tools, and arm/hand bones ( Corballis , 1989; Steele, 2000) right-handedness prevalent in all human cultures before effects of culture: more than 9 of 10 fetuses suck the right hand’s thumb in the womb ( Hepper et al., 1990, 2004) chimpanzees and gorillas (closely related to humans) = 65% right-handed (Hopkins et al., 2005) other, more distant primates are more evenly split

ARBORAZATION:

ARBORAZATION 3/27/2011 33

SPECIAL FEATURES OF NERVOUS SYSTEM:

SPECIAL FEATURES OF NERVOUS SYSTEM 3/27/2011 34

BASIC FUNCTIONAL UNIT:

BASIC FUNCTIONAL UNIT 3/27/2011 35

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Nervous Tissue:

Nervous Tissue Highly cellular 2 cell types Neurons Functional, signal conducting cells Neuroglia Supporting cells 3/27/2011 37 1. 2.

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1 .COMPARISION WITH COMPUTORS 3/27/2011 38

COMPARISION WITH COMPUTORS:

COMPARISION WITH COMPUTORS INPUT OUTPUT CENTRE INTEGRATION SPEED NEW IDEAS ENERGY PROPER CONNECTIONS INSULATION DAY DREAMING OUTPUT FLEXIBILITY ORGINALITY 3/27/2011 39

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Computers vs. Brains:

Computers vs. Brains Processing elements: There are,108 transistors R 10 synapses Processing speed: 109 Hz Intelligence and consciousness: the computer shows lack of intelligence. Evolution: computers have been evolving for decade s Brain 100 Hz 2. The brain is highly intelligent and conscious. 3.The brains have been evolving for tens of millions of years, 3/27/2011 41 14

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Fault tolerant: whereas the computer is not. Adaptive: whereas the computer doesn’t even compare with an infant’s learning capabilities. 3. Style of computation: whereas the computer mostly serially and centralized Fault tolerant: The brain is fault tolerant Adaptive: The brain learns fast. The brain computes in parallel and distributed mode, 3/27/2011 42

Neuroscience in the news :

Neuroscience in the news 1.relatively recent 2.interdispilanary 3.uses many levels of analysis Organisms (behavior) Systems Circuits Neurons Molecules 4. Neuro -genesis Growth of new neurons Once thought impossible 3/27/2011 43

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. 1. Stem cells research , Immature cells that renew themselves and have the potential. to develop into mature cells 2.Embryonic stem cells are most useful Controversial 3.In 2001, President U.S.A signed executive order preventing creation of new cell lines. 4.Some scientists want the ban lifted 3/27/2011 44

2.LACK OF LYMPHACITIC SYSTEM:

2. LACK OF LYMPHACITIC SYSTEM 3/27/2011 45

3. DEVELOPMENT:

3. DEVELOPMENT 3/27/2011 46

4.Neural Induction:

4. Neural Induction Induction signals From embryonic tissue Modulate gene expression Retinoic acid Steroid hormone Peptide hormones Fibroblast growth factor (FGF) Transforming growth factor (TGF) 3/27/2011 47

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Neuronal structure develops in 4 major stages: Proliferation,N eurogenesis Migration Differentiation Synaptogenesis 3/27/2011 48

5. .Development of the neuronal structure physiologically occurs in 8 stages :

5. .Development of the neuronal structure physiologically occurs in 8 stages Mitosis/Proliferation Migration(rate=6-10µm/min) Differentiation Aggregation Synaptogenesis Neuron Death Synapse Rearrangement Myelination

Stages of Development :

Stages of Development target identification migration neurogenesis axonal extension synaptogenesis morphological differentiation 3/27/2011 50

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6 .Critical Periods in Human Development Embryonic development (9 week) Fetal development (until birth) Postnatal development e.g. Critical period for language acquisition 3/27/2011 51

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7. MATURATION 3/27/2011 57

8. NEUROPLASICITY:

8. NEUROPLASICITY Development Activity Learning Habituation Response to injury Rehabilitation 3/27/2011 58

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9 stimulating environment increases dendritic branching and number of dendritic spines:

9 stimulating environment increases dendritic branching and number of dendritic spines 3/27/2011 60 Standard environment Enriched environment

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3/27/2011 62 10 .DESTRUCTION 1..one-year old human has about 100 billion (10 11 ) neurons . 2. No new neurons will be formed after that age, ? ? ? 3.neurons will be lost at a rate of roughly 200,000 per day (a net loss of 2 to 5% by age 50). 4.Maximum brain weight is achieved at about age 21 5.Hypothalamus is the last to deverlope compeletly

10. RMP= -65mV:

10. RMP= -65mV ------ -65 -65-65 - 65 63

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3/27/2011 64 11 .NUMBER OF THE CELLS Guess what? There are more nerve cells in the human brain than there are stars in the Milky Way.

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3/27/2011 65 The Human Brain 100 billion 1 billion In The Spinal Cord

A single neuron on the surface of a microprocessor A cm3 of the brain will contain >50 million neurons:

A single neuron on the surface of a microprocessor A cm3 of the brain will contain >50 million neurons 3/27/2011 66

12.Number of neurons &connections in the cortex alone 12-15 billons+60 trillion :

12 .Number of neurons &connections in the cortex alone 12-15 billons+60 trillion Number of neurons cerebellum= 70 billons 3/27/2011 67

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3/27/2011 69 11 . DIFFERENT TYPES 50 MILLION DIFFERENT CELLS

13. PRODUCTION 1/3 million per min in 9 months of gestation :

13 . PRODUCTION 1/3 million per min in 9 months of gestation 3/27/2011 70

14.LOSS OF DIVIDING PROPERTIES :

14 .LOSS OF DIVIDING PROPERTIES 3/27/2011 71

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15.Binary code Principle:

15 . Binary code Principle -encode information at the cellular level. Neurons encode information by the Frequency modulation On and Off mechanism of electrical impulses, controlled by chemical signal(NT) from other cells . 3/27/2011 73

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FREQUENCY CODE 1. 2. 3. Weak stimulus Moderate stimulus Strong stimulus

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Frequency of Action Potential Firing is Proportional to the Size of the Graded Potential The amount of neurotransmitter released from the axon terminal is proportional to the frequency of action potentials .

16. BUOYANCY:

16 . BUOYANCY 3/27/2011 76

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CSF is a watery “ broth”found in and around the brain and spinal cord It forms a liquid cushion that gives buoyancy to the CNS organs With the brain floating, CSF reduces brain weight by 97% and thus prevents the brain from crushing under its own weight 3/27/2011 77

17. ASYMMETRICAL FUNCTIONING IN THE BRAIN:

17 . ASYMMETRICAL FUNCTIONING IN THE BRAIN 3/27/2011 78

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18.SEX DIFFERENCE IN LATERALISATION OF LANGUAGE:

18 .SEX DIFFERENCE IN LATERALISATION OF LANGUAGE 1. MALES ------LEFT HEMISPHERE ACTIVATION ONLY 2. FEMALES SHOW LEFT & RIGHT 3/27/2011 80

19.Sexual Dimorphism In Grey Matter Thickness (MRI) :

19. Sexual Dimorphism In Grey Matter Thickness (MRI) Note women have more grey matter on the right(0.45 mm thicker) inferior parietal and posterior temporal areas 3/27/2011 81

20 .LENGTH OF NERVOUS SYSTEM:

20 .LENGTH OF NERVOUS SYSTEM 3/27/2011 82

LENGTH OF THE CELL IN THIS SYSTEM (NEURON):

LENGTH OF THE CELL IN THIS SYSTEM (NEURON) 3/27/2011 83 AXON 0.1 - 1,000 mm length thin, uniform width SOMA DENDRITES

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21 .Longest cell blue whale neuron 10-30 meters giraffe axon 5 meters human neuron 1-2 meters 3/27/2011 84

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one neuron is about 10 microns long. Remember, this is just an example, because neurons come in all different sizes. So, if we line up 100 billion neurons which are 10 microns long . . . 100,000,000,000 neurons x 10 microns= 1000 km or about 600 miles! This may help with the math: 1000 microns= 1milimeter (mm) 10 mm= 1centimeter (cm) 100 cm= 1 meter (m) 1000 m= 1 kilometer (km) 3/27/2011 85

22.PARTCIPATION OF GENE tissue-specific gene expression.:

22 .PARTCIPATION OF GENE tissue-specific gene expression . 3/27/2011 86

23.AMOUNT OF mRNA PRODUCTION:

23. AMOUNT OF mRNA PRODUCTION 3/27/2011 87

24.NKP:

24 .NKP 3/27/2011 88

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Neuropil:

Gray Matter Neuropil - neuronal processes, synapses and glia G/C COEFFCIENT=47 IN OCCIPITAL LOBE HUMAN 11 IN MOUSE Neuropil 90 Lecture II. The Nervous System and Its Cells

25.B.M.R 1. 7.5 TIMES THAN THE NON- NERVOUS TISSUES 2. Children have twice the metabolic rate/ unit vol. than the adults :

25 .B.M.R 1. 7.5 TIMES THAN THE NON- NERVOUS TISSUES 2. Children have twice the metabolic rate/ unit vol. than the adults 3/27/2011 91

26.1.Weight 2-3% of body 2.O2 Consumption 20% of total 3.Brain Energy (Glucose) Utilization 20% of total 4.Brain Blood Flow 20% of heart output at rest:

3/27/2011 92 26.1. Weight 2-3% of body 2. O 2 Consumption 20% of total 3. Brain Energy (Glucose) Utilization 20% of total 4. Brain Blood Flow 20% of heart output at rest

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3/27/2011 93 27. FASTEST RESPONSE Nervous system allows for 1 millisecond response time

28.HOMOESTSIS:

28. HOMOESTSIS 3/27/2011 94

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Nervous vs. Endocrine System:

Nervous vs. Endocrine System 3/27/2011 96

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Chapter 4 Principles of Neural and Hormonal Communication Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Comparison of Nervous System and Endocrine System

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Hypothalamus Autonomic nervous system Neuroendocrine Brain stem and spinal cord Pituitary Maintain body homeostasis 3/27/2011 99

METHODS OF NEUROPHYSIOLOGY STUDIES:

METHODS OF NEUROPHYSIOLOGY STUDIES 1. Microscopic a. Light microscopy b. TEM , SEM and freeze fracture C) Sharp metal and glass-filled electrodes plus suction electrodes for patch clamp technique 2. Cathode Ray Oscilloscope 3. Stains (1) Methylene blue (2) Cobalt filling (3) Fluorescent-Lucifer yellow and dextran-rhodamine (4) Immunological stains (fluorescent antibodies) 100

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3/27/2011 101 4.Histological Analyses

5.Computed tomography (CAT) :

5.Computed tomography (CAT) 3/27/2011 102

6.Magnetic Resonance Imaging (MRI):

6.Magnetic Resonance Imaging (MRI) 3/27/2011 103 Use electromagnetic fields to image atom (hydrogen) density Scan living brain Protons (H + ) respond to magnetic field High resolution Expensive

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3/27/2011 104 7.Functional MRI

8.CLINICAL PHYSIOLOGY:

8.CLINICAL PHYSIOLOGY 3/27/2011 105

9.Positron Emission Tomography (PET):

9.Positron Emission Tomography (PET) 3/27/2011 106

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3/27/2011 107 Optical Imaging & TMS

10.Electroencephalogram (EEG):

10.Electroencephalogram (EEG) 3/27/2011 108

11. Behavioral Neuroscience: Animal Experimentation:

11. Behavioral Neuroscience: Animal Experimentation 3/27/2011 109

EFFCTS OF AGE (BRAIN):

EFFCTS OF AGE (BRAIN) 1.Enlargement of the volume of the ventricles: because cells surrounding the ventricles are lost 2. Widening of sulci (the grooves) on the surface of the brain 3. Reduced brain weight and brain volume: caused by the loss of neurons. 4. Loss of NT 5. Neurological disorders: brain disorders Alzheimer’s disease, Parkinson's disease and stroke 3/27/2011 110

EFFCTS OF AGE CORD +NERVES:

EFFCTS OF AGE CORD +NERVES 3/27/2011 111 Myelin sheath increases- 1 st sensory in foetal life than motor after birth Axon increases in length Arborization increases Synaptic connections increases

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Glial tissue increases Neuronal size increases 11.Loss of neurones 40% with age more in males than females 3/27/2011 112

HOMUNCULUS:

3/27/2011 113 HOMUNCULUS

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Definition of death:

Definition of death Traditionally Doctor Declare A Person Dead When His Heart & Respiration Stops Recent Times Both The Things Can Be Maintained Artifiically For Longer Times For Organ Transplant And Resumption An EEG Silence R Brain Death Is An Accepted Creteria If The Subject Should Be In Coma And Apnoea For 6 Hours Following Which EEG Silence Is Present Continously For At Least 30 Minutes. No Legal Definition EEG Silence Is Defined As Absence Of Electrical Potential Over 2mv. From Symmetrical Placed Electrodes Pairs Over 10 Cms . Apart With An Inter Electrode Resistance Between 100-1000 Ohms. 3/27/2011 115

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Development Aspects of the Nervous System The nervous system is formed during the first month of embryonic development Any maternal infection can have extremely harmful effects 3/27/2011 116

SUMMARY Interesting Facts :

SUMMARY Interesting Facts 3/27/2011 117 1 A newborn baby's brain grows almost 3 times during the course of its first year. 2. Your brain is made mostly of water . (85%) 3. A New born baby loses about half of their nerve cells before they are born. 4. As we get older, the brain loses almost one gram / year. 5. The total surface area of the human brain is about 25, 000 square cm. 6. The base of the spinal cord has a cluster of nerves, which are most sensitive.

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7. An average adult male brain weighs about 1375 grams . 8. An average adult female brain is about 1275 g rams. 9. 4% percent of the brain's cells work while the remaining cells are kept in reserve. 10.Gray matter 3 time > white matter 11. No O2 reserve – loss of consciousness in 10 seconds – irreversible damage in 3-5 minutes 3/27/2011 118

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3/27/2011 119 SOME RECENT FACTS ABOUT NERVOUS SYTEM Precursor cells can give birth to new neurons when immersed in a growth-promotion protein Physical and mental exercise promote the survival and the production of new precursor cells Stress can prohibit the production of new cells Nicotine can kill precursor cells