Evolution-Of-Nervous-System YouTube Lecture Handouts
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5 Parts of the Embryonic Vertebrate Brain
Evolution of Nervous System
- History of evolution goes millions & millions & millions of years back
- From an unicellular organism to the most complex form
- All systems evolved
- Nervous System evolved very rapidly and is perhaps still evolving.
Brain Body Weight Ratio
Organization of Nervous System
Two parts
- Central N. S. Occupies the central axis of body
- Peripheral N. S.
- Somatic N. S.
- Autonomic N. S.
Central Nervous System
Includes:
- Brain
- Fore brain
- Mid brain
- Hind brain
- Spinal cord
1 Fore Brain
- Telencephalon
- Cerebral hemispheres
- Diencephalon
- Thalamus
- Hypothalamus
2 Mid Brain
- Ventral part
- Tegmentum, substantia nigra & basis peduncle
- Dorsal part
- Tectum constituting superior & inferior Colliculi
3 Hind Brain
- Includes
- Pons
- Medulla Oblongata
- Cerebellum
Brain Stem
A commonly used term includes
- Midbrain
- Pons
- Medulla
Spinal Cord
Begins from foramen magnum & terminates at lower border of I lumbar vertebra. Below this it forms Cauda Equine
Cross Section of Spinal Cord
- In the brain stem & spinal cord
- White matter surrounds the grey matter
- In the cerebrum & cerebellum
- Grey matter surrounds the white matter
- Fatty myelin gives white appearance
- Cell bodies of neurons provide a grey colour (ash colour) to grey matter
Gross Section
- Post. Horn … Sensory
- Anterior Horn-Motor (α, γ motor neurons & Renshaw cells)
- Intermediate Horn-Sympathetic fibers
BELL- MAGENDIE LAW
In spinal cord Dorsal roots are sensory & Ventral roots are motor
Peripheral Nervous System
- Somatic N. S.
- Cranial Nerves
- Spinal Nerves
- Autonomic N. S.
- Symp.
- Parasymp.
Cranial Nerves
12 pairs, cell bodies are in the brain
- Sensory … I, II & VIII
- Motor … XI & XII
- Mixed … III, IV, V, VI, VII, IX & X
Spinal Nerves
31 pairs
- Cervical … 8 pairs
- Thoracic … 12 pairs
- Lumbar … 5 pairs
- Sacral … 5 pairs
- Coccygeal … 1 pairs
Cells in Nervous System
Two types
Glial cells & Neurons
Glial Cells
- 10 to 50 times more than neurons
- Supporting cells
- Do not generate Action Potential
- Retain the ability to divide & multiply throughout the life
Glial Cells … Types
1 Macroglial cells: Ectodermal in origin
Oligodendrocytes
Astrocytes
Fibrous astrocytes, in white matter
Protoplasmic astrocytes, in gray matter
2 Microglial cells: Mesodermal in origin
Microglia
3 Ependymal cells
Oligodendrocytes
- Round or pear shaped
- Function: formation of myelin sheath
- Give multiple processes to form myelin on many neurons, about 20.
- Their counterpart in peripheral nervous system are Schwann cells
- Nerve fibers in CNS have no neurilemma. So once degenerated, never regenerates
- Multiple sclerosis: an autoimmune crippling disorder shows patchy destruction of myelin in CNS.
Astrocytes
- Star like in shape
- Functions:
- Form Blood Brain Barrier
- Produce substances trophic to Neurons
- Maintain concentration of ions and Neurotransmitters.
Microglia
- Are scavenger cells
- Function as phagocytes
Ependymal Cells
Are epithelial cells that line?
CSF filled ventricles in the brain & Central canal of the spinal cord
Neurons
Important Facts:
- Total No. of Neurons in CNS about (1011) 100 billion
- Neurons cannot multiply as they have no centrosome
- All neurons present at the time of death were present since birth
- Regeneration in neurons: some evidences of regeneration are present at few sites
- Hippocampus
- Some areas in cerebral cortex
- Dopaminergic neuron in Substantia Nigra
- Each neuron forms about 2000 synaptic endings
- Total no. of synapse about
- New synapse formation occurs throughout the life & is the basis of learning & memory
Neuron Classification
Classified
Depending upon number of poles from which processes arise
- on functions
- upon length of axons
No. Of Poles
- Unipolar: in embryonic stage
- Pseudo unipolar: primary sensory neurons conveying impulses from sensory receptors to spinal cord
- Bipolar: in vestibular & cochlear ganglia, bipolar cells of retina
- Multipolar: most neurons
Types of Neurons
2 Depending on functions
- Sensory
- Motor
3 Depending on length of axon
- Golgi type I: have long axons eg. Neurons forming peripheral nerves & long tracts of brain and spinal cord.
- Golgi type II: short axons, eg. Numerous neurons in cerebral cortex & cerebellar cortex
Structure of Neuron
Has three parts
- Dendrites
- Cell body
- Axon
Structure of a Neuron
Dendrites
- Extends out of cell body
- 5 to 7 in no.
- Arborize extensively
- Have dendritic spines
- Form receptive end of neuron
Cell Body
- Nissl Granules: rough endoplasmic reticulum, synthesize proteins, required for production of neurotransmitters & for repair. They are not seen in axon
- Centrosome not present: it shows loss of ability for division. Nerves once destroyed are replaced by glial cells
Axon
- Long fiber
- Initial part is Axon Hillock
- First portion forms Initial Segment
- At terminal end synaptic knobs are present also called Terminal buttons or Axon telodendria
- Knobs contain synaptic Transmitters
Synapse
- Definition: means Clasping of hands as in hand shaking. First described by Sherrington as the site of contiguity (no anatomical continuity)
- At these sites neurons make functional junctions with each other
- Impulses are passed from one neuron to other neuron
- Total no. of synapse about
- New synapse formation occurs throughout the life & is the basis of learning & memory
Classification
Two types
- Anatomical
- physiological
Classification
Anatomical
- Axo dendritic: most common eg. Motor neurons in spinal cord, neurons in cerebral cortex & climbing fibers in cerebellum
- Axo somatic: eg. Motor neuron in spinal cord, basket cells of cerebellum, autonomic ganglia
- Axoaxonal: Spinal cord- presynaptic inhibition
- Dendro dendritic: eg. Between mitral & granular cells in olfactory bulb
Dendro- Dendritic
Physiological Classification
- Electrical
- Conjoint
- Chemical
Electrical Synapse
- Transmission through gap junctions
- Seen in Lateral Vestibular Nucleus, hippocampus & cerebral cortex
- Transmission is in both directions
- No delay
Conjoint Synapse both electrical & chemical transmission present.
Chemicalâź‹Electrical Synapse
Chemical Synapse
- Structure
- Changes in postsynaptic membrane
- Electrical, (development of EPSP & IPSP)
- Ionic
- Development of Action potential in post. Synaptic neuron
- Removal of transmitter
Structure
Includes
- Synaptic knob of pre synaptic neuron
- Synaptic cleft
- Post synaptic membrane
Synaptic Knob
- No. of knobs —
- One per synapse in mid brain
- 10,000 spinal cord
- Knobs contain Synaptic vesicles
- Small clear … Acetylcholine, glycine, GABA glutamate
- Small dense core … Catecholamines
- Large dense core … Neuropeptides
Synaptic Cleft
- Is a gap of 20 to 30 nm
- Filled with some fluid & glycoproteins
- Separates pre & post synaptic membranes
Postsynaptic Mem
- Sub synaptic mem.
- Is membrane involved in the synapse
- Receptors are usually present here
- Post Syn. mem.
- Remaining part of mem.
Changes at Synapse
- Release of neurotransmitter from presynaptic terminal
- Electrical changes in sub synaptic & postsynaptic membrane, means development of EPSP or IPSP
- Ionic changes
- Removal of neurotransmitter
Release of Neurotransmitter
- Nerve signal comes to terminal ending
- Ca++ enters in the ending & causes
- Release of neurotransmitter by exocytosis
- Transmitter acts over post synaptic mem.
Electrical Changes
- Depending upon the type of neurotransmitter EPSP or IPSP is generated on sub synaptic membrane
- Action of neurotransmitter occurs within ms.
- Usually all endings of one neuron contain only one type of transmitter, but there are examples where neurons contain & secret two or even three types of transmitters
Co-Transmittersâź‹Neuromodulators
Eg.
- Many cholinergic neurons contain VIP
- Many adrenergic & N. A. neurons contain ATP & neuropeptide Y.
- Physiological significance is not clear but can potentiate the action
EPSP and IPSP
Excitatory Post Synaptic Potential (EPSP)
- Transmitter usually glutamate
- Depolarization of Postsynaptic mem.
- Starts with a latency of 0.5 msec.
- Peaks in 1 to 1.5 msec
- Decline with a half-life of 4.0 msec. (Declines exponentially)
Ionic Changes in Gen. Of EPSP
- Excitatory transmitter acts over sub synaptic mem.
- Na+ or Ca++ channels open
- Only EPSP is produced as the current generated is small
- EPSP can also be produced by agents that close K+ channels
Inhibitory Post Synaptic Potential (IPSP)
- Transmitter, Glycine or Gama Amino Butyric Acid (GABA)
- Post Synaptic mem. is hyperpolarized
- Latency 1 to 1.5 ms
- Peaks 1 to 2 ms
- Decreases exponentially with a time constant of 3 ms
Ionic Changes
- Increase in Cl- transport
- IPSP can also be produced by
- Opening of K+ channels
- Closure of Na+ and Ca++ channels
Slow EPSPs and IPSPs
- Are seen in autonomic ganglia, cardiac & smooth muscles and cortical neurons
- Latency of 100 to 500 ms
- Lasts for several seconds
- They are due to change in conductance of K+
Genesis of Action Potential in Post Synaptic Neuron
FACTS
Electrical activity in one synapse is not adequate enough to stimulate post synaptic neuron
Threshold is lowest at initial segment of neuron
Synaptic integration: all EPSPs & IPSPs are summated, net algebraically summed potential determines whether transmission of impulse will take place or not.
If Summated potential is 10 to 15 mv spike potential is generated at Initial segment of neuron
IS spike leads to further Depolarization of 30 to 40 mv? & Action potential is produced
Action Potential is only produced at Initial segment
Action Potential Travels in Both Directions
- Peripherally as nerve impulse
- Centrally towards soma & dendrites so as to clear existing EPSPs & IPSPs & Cell is once again ready to react to another set of stimuli
Inactivation of Neuron
Chemical transmitter is removed
- Diffusion out of cleft
- Enzymatic degradation
- Reuptake by pre synaptic knob
Properties of Synapse
- Law of forward conduction
- Synaptic Delay
- Convergence & Divergence
- Summation
- Occlusion
- Subliminal fringe
- Fatigue
- Synaptic plasticity & learning
- Response to hypoxia
Law of Forward Conduction
Because of the specific structure, neurons permit conduction of impulse from pre to post synaptic neuron only
Synaptic Delay
Minimum time required for transmission at one synapse. It is required for
- Release of neurotransmitter
- Diffusion up to post synaptic membrane
- Activation of receptors
- Ionic changes to generate EPSP or IPSP
- Minimum time is 0.5 ms at one synapse
Convergence & Divergence
Summation
Two types
- Spatial: if two afferents are stimulated simultaneously with sub threshold stimuli, their EPSPs get summated and spike is generated
- Temporal: if an afferent is stimulated in quick succession (before the decay of first stimulation) again a response may be there.
Occlusion: Due to Overlapping
Subliminal Fringe
Fatigue
- Repeated stimulation of pre synaptic neuron finally leads to disappearance of the post synaptic response
- Causes:
- Exhaustion of chemical transmitter, as synthesis is not as rapid as release
- Inactivation of channels
Synaptic Plasticity
- Plasticity is capability of being easily modulated
- Means synaptic transmission can be increased or decreased on the basis of past experiences
- It makes the basis of learning
- Changes at synapse are
- Post Tetanic Potentiation
- Long Term Potentiation
- Habituation
- Sensitization
Hypoxia
Synapses are more susceptible to hypoxia than the nerve fibers
Synaptic Inhibition
Types:
- Post synaptic inhibition
- Direct
- Indirect caused by some previous activity
- Pre synaptic inhibition
- Negative feedback inhibition
- Feed-forward inhibition
Post Synaptic – Direct Inhi
- IPSP is generated on post synaptic neuron
- Bi-synaptic path way eg.
Reciprocal Innervation in spinal cord
- Means if flexors are contracting the extensor group will relax
- Present in spinal cord the inter neuron is Golgi Bottle Neuron it liberates Glycine
Reflex from Golgi Tendon Organ
- If muscle is stretched strongly, it relaxes
- Receptor … Golgi Tendon Organ
Indirect Inhibition
May be because:
- Post synaptic neuron has just fired, so refractory
- During after hyper polarization neurons are less sensitive
Presynaptic Inhibition
- It occurs at the presynaptic terminal before the signals reach at the synapse
- Synapse is Axo-axonal
- Transmitter secreted is (GABA) gamma-amino butyric acid
Mechanisms
- Receptors are GABAA
- 1 Activation of presy. neuron increases
- conductance & decreases size of A. P. reaching the excitatory ending
- This reduces
- entry & at the same time decreases amount of transmitter released
- channels open & efflux also decreases the influx
- 3 direct inhibition of transmitter release independent of Ca++ influx
- receptors are also present & they act by G protein- mediated effects on potassium channels
Negative Feedback Inhibition
- Seen in spinal cord
- Also called Renshaw cell inhibition
- Here neurons inhibit themselves in a negative feedback fashion
- Neurons check their own discharge
Feed Forward Inhibition
Seen in cerebellum
Applied Aspects of Synaptic In
- Myelinated cutaneous afferents affect pain sensation by pre synaptic inhibition
- Pre synaptic inhibition is antagonized by the convulsant drug Picrotoxin
- Barbiturates greatly pronounce pre synaptic inhibition
- Convulsant effect of strychnine is due to depression of post synaptic inhibition
Receptors
- Are like transducers that convert various types of energies into electric energy.
- These are modified nerve endings
- They have punctate character
- All sensory information do not necessarily reach the level of consciousness.
Classification
A According to the type of receptors
SherringtonŐšs classification
- Telereceptors: hearing, vision, smell.
- Exteroceptors: touch, temp, pain
- Interoceptors: proprioceptors, chemoreceptors, visceroceptors
B General or Anatomical classification
- Special senses: smell, vision, hearing
- Superficial or cutaneous senses: touch, temperature, pain, pressure
- Deep senses: sensation from joints, muscles, tendons
- Visceral senses: visceral pain
C According to type of stimulus
D According to degree of Adaptation
- Tonic: slow adaptation, receptors continue to send information for hours or even for days eg.
- Muscle spindle
- Pain
- Cold
- Phasic: Show Rapid adaptation eg.
- Touch
- Pressure
- No adaptation
- Pain
- Vestibular receptors
E Epicraticâź‹Protopathic
- Epicratic Sensation: Mild or light sensation perceived more accurately eg. Fine touch, tactile localization, and tactile discrimination, temp. Between 2
- Protopathic: Primitive or crude sensation eg. Pressure, pain, temperature below
CUTANEOUS RECEPTORS
- Touch: MeissnerŐšs corpuscle, MerkelŐšs disc RuffiniŐšs end organs KrauseŐšs end bulb & free nerve endings around hair roots
- Temperature:
- Cold … Nerve Endings of type A δ fibers (myel.)
- Warm … Nerve Endings of Type C fibers (unmye.)
- Pain: Free nerve endings
- Deep pressure: Pacinian Corpuscle
- Proprioception:
- Muscle Receptors
- Pacinian Corpuscles
- Uncapsulated nerve endings.
- Synthetic senses
Touch Sensation
Two types:
- Crude touch – perception of touch
- Fine touch
- Tactile localization
- Two point discrimination
Temperature Sensation
Cold receptors are 4 to 10 times more.
- Types:
- myelinated for cold
- C unmyelinated for warm
- Present all over the body. Density-
- Greatest … in the lips
- Moderate … finger tips
- Least … trunk
Difference between Cold & Warm Receptors
Paradoxical Cold Response
- If tissue temp. is beyond it leads to tissue damage & damage to cold receptors sometimes stimulate them & their discharge produce a sensation of cold
- Probably above tissue damage begins
Otherâź‹Synthetic Senses
- 2 point discrimination: depends on density of rec.
- Lips & finger tips … 2 to 3 mm
- Back of trunk … 60 mm
- Vibration: Receptors are rapid adapt.
- Pacinian corpuscle
- MeissnerŐšs corpuscles
- Krause bulb
- Lost in
- Tabes Dorsalis
- Peripheral neuropathies (diabetes)
- Post. Column disorders
- Stereognosis … Ability of person to identify common objects with closed eyes
- Receptors – touch & pressure with their central connections and cerebral cortex
- Astereognosis: loss of this ability. It is an early sign of damage to Parietal Lobe but receptor & conn. should be normal
- Itch: irritating condition caused by mild stimulation of skin eg. flea crawling on the skin. Can also be produced by chemicals like Bile salts, histamine, kinins, Itch powder etc.
- Receptor- naked N. E. of type C fib.
- Scratching relieves it. by presynaptic Inhibition in Dorsal horn cells (like pain)
- Tickle: is another variable of touch. It is regarded as pleasurable feeling
Activation of Receptors
- Receptor can be stimulated by specific stimulus Stimulation of receptor produces
- Electrical changes: generation of receptor potential
- Ionic changes
Receptorâź‹Generator Potential
- Is widely studied in Pacinian Corpuscles as they are big in size.
- Structure: a straight unmyelinated sensory nerve ending is surrounded by concentric lamellas of connective tissue
- I node of Ranvier is inside the corpuscle
- II node is located outside
- P. C. can be stimulated mechanically by a glass rod
- With small pressure a non-propagating potential is generated. This is Receptor or Generator potential
- Receptor potential is local potential produced in unmyelinated nerve terminal
- Receptor pot. Of ~10 mv. is capable to produce Action Potential
- It depolarizes nerve at First Node of Ranvier
- Action potential is produced only at I node of Ranvier
- As pressure is increased Receptor Potential becomes larger & nerve fires repetitively (increase in rate of firing)
Conclusion
- Generatorâź‹receptor potential originates from unmyelinated nerve ending
- Action potential is produced at I node of Ranvier
Ionic Changes
- Increase in permeability for sodium ions in unmyelinated terminal
- Degree of permeability is directly related to the intensity of stimulus
Weber Fechner Law
- Gradations of stimulus strength are discriminated approximately in proportion to the logarithm of stimulus strength
- Magnitude of the sensation felt is proportionate to the log of the intensity of the stimulus. However a power function describes it more accurately
- R is sensation felt
- S intensity of the stimulus
- K & A are constants.
Coding of Sensory Information
Questions to be considered
- All nerves carry electric signals than, how different sensation are produced?
- How the site of stimulation is localized?
- How the grading of sensation is done?
Possible mechanisms
- MullerŐšs Doctrine of specific nerve energies
- Law of Projection
- Grading of sensation
MullerŐšs Doctrine
Principle was first enunciated by Muller in 1835
- The specific sensory pathways are discrete from sense organs to brain. If this pathway is stimulated anywhere, the sense evoked is that for which the receptor is specialized.
- If a growth in spinal cord presses the pain pathway, the sensation felt is of pain.
Law of projection
- No matter where a particular sensory pathway is stimulated along itŐšs course from receptor to the cortex, the conscious sensation produced is referred to the site where receptor is located. eg.
- Phantom Limb, a person who has lost his limb in an accident or amputation, usually experiences intolerable pain and other sensations in the limb that is no longer there. It is because of irritation of afferent nerves at the stump, where a neuroma is formed.
Intensity Discrimination
- 1 By frequencies of Action Potentials generated in the sensory nerve fibers. Frequency directly depends on strength of stimulus
- 2 By number of recruitment of sensory units, as the strength is increased more and more units start firing
Properties of Receptors
Law of Adequate stimulus
- Receptors response maximally to a specific stimulus
Adaptation
- Tonic: slow adaptation, receptors continue to send information for hours or even for days eg.
- Muscle spindle
- Pain
- Cold
- Phasic: Show Rapid Adaptation eg.
- Touch
- pressure
Sensory Unit
- It includes single sensory axon and all itŐšs peripheral branches. Sensory units generally overlap