Introduction to neuroscience

1
Introduction to neuroscience

• By David William Harper
• Illustrations adapted from Biological
  Physiology 7th edition by J. W. Kalat
• Text adapted from notes by SJN

2
Recommended Text

• J. W. Kalat, Biological Physiology, Edition 7,
  Wadsworth
• Bear et al, neuroscience

3
The Major Issues
4
The mind-brain relationship

• It is to try to understand what we think
• understand human thinking
• why we are different from robots
• Its fundamental to understand the principle of
  how it works because it is the base of all
  physical biological methods
• Our view will be biological

5
Biological explanation of behaviour

• Most scholars agree that the mind does not exist
  independently of the brain
• Biological physiology the study of the
  physiological, evolutionary and developmental
  mechanisms of behaviour and experience
• Physiological explanation relates behaviour to
  the activity of the brain
• Ontogenetic explanation influences of and
  interactions between genes, nutrition and
  experiences producing behaviour
• Evolutionary explanation relates behaviour to
  the evolutionary history
• Functional explanation describes why a
  behaviour involved in a particular way (different
  areas etc.)

6
The brain and conscious experience

• What is the mind and how it affects body (brain)
• philosophers tried to answer that question for
  many years
• Its important to understand different positions
  and how our minds the affect our bodies

7
mind-body problem

• what is the relationship between mind and the
  brain?
• Potential views
• Dualism
• Body is one material
• Mind is another material
• They are not necessary to be extremely different
  but they are different properties
• Not necessary to be completely different
• Monism
• The universe consists of only one type of
  existence, either
• materialism - everything is physical
• mentalism - only the mind really exists
• identity position the mental processes are the
  same as some brain processes
• Solipsism
• the problem of other minds

8
Philosophers

• Chalmers
• He said that we can separate the problems into
  two classes
• easy problems
• Neuroscientist has a link between 3rd person and
  1st person
• Collecting empirical information
• New technology with advances
• We can answer easy questions in a definite
  manner
• Each function of easy can be indentified to a
  particular area/mechanism
• hard problems
• Cannot be resolved
• Subjective - smell of roses
• Different experiences between people
• qualia, i.e. particular qualities, subjective
  experience cannot be explained in mechanistic
  terms
• consciousness is a fundamental property of matter
  it cannot be explained

9
Philosophers

• Dennett
• no hard problems - once all the easy problems are
  explained then there will be nothing left
• Disagreed with traditional carthage theatre of
  mind
• Different processes compete with each other for
  the spot light or access to consciousness
• multiple draft theory of mind
• Multiple processes running like a river
• Continually being revised/changed by joining
  river
• Churchland
• consciousness may have conventional physical
  explanation

10
Nature and Nurture
11
Genes

• Genes
• units of heredity maintaining their structural
  identity throughout generations.
• fragments of DNA (deoxyribonucleic acid)
• used by organisms to code for different proteins
• they consist of a series of so called nucleotides
  and have generally a similar general structure
• They come in pairs because they are parts of
  chromosomes.
• Chromosome
• A double-strand of DNA (i.e. strands of genes)
• Contained in the cell nucleus
• In the process of transcription, information it
  encodes is used to form RNA.
• Chromosomes also come in pairs
• RNA (ribonucleic acid)
• transported from nucleus to the ribosomes
  ("protein factories") where it's "programme" is
  translated into a sequence of aminoacids - a
  protein.
• DNA gt RNA gt protein synthesis
• (structural proteins and enzymes biological
  catalyst regulating body biochemical reactions)

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Genes

• Homozygous individual
• one which has a pair of identical pair of genes
  on the two chromosomes
• Heterozygous individual
• has unmatched pair of genes
• Genes can be either
• Dominant
• shows a strong effect in both hetero- and
  homozygous condition
• Recessive
• shows effects only in the heterozygous condition

13
Behaviour

• Genes influence behaviour directly by changing
  chemicals in the brain and indirectly by
  affecting the body
• However Genes are not the full picture because we
  are continuing to develop subject to external
  circumstances / environment

14
History of Neuroscience
15
A history of neuroscience

• Before Hippocrates, people associated different
  organs with thoughts/feelings
• Theories are reflective of their time and the
  knowledge available then.
• Egyptians did not consider that the brain
  mattered and did not preserve it with other
  organs for mummification

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A history of neuroscience

• Hippocrates
• first to ascribe sensation and intelligence to
  the brain (before him people thought that the
  mind was located in a hart or in the gut)
• Galen
• humors (fluids) theory
• personality traits are due to different
  concentration of humours
• Descartes
• tried to explain the relationship between mind
  and the body
• The brain was material and fluid-mechanical (like
  a hydraulic system of pipes) and supposed to
  communicate with the mind via pineal gland, the
  only asymmetrical organ in the brain
• pure reason - emotions and the logical mind are
  separate from each other
• Galvani
• considered nerves as wires
• discovered that brain is using electricity for
  communication

17
A history of neuroscience

• Gall
• invented phrenology (the study of correlating the
  structure of the head with the personality
  traits)
• Broca
• proposed localisation of function
• each cognitive function had a corresponding
  region in the brain that generated it
• Golgi
• proposed nerve net view of the brain
• considered all the neurons to form a single
  connected system
• Discovered method of staining neurons to see the
  structure which helped to establish Gajals ideas
• R. Y Cajal
• discovered that neurons act as functional units
  and are actually disconnected from each other

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Neuroscience Today

• Levels of Analysis
• molecular neuroscience
• cellular neuroscience
• systems neuroscience
• behavioural neuroscience
• cognitive neuroscience
• Research methodology
• predominantly experimental
• some mathematical and computational modelling

19
Neural System Disorders

• Alzheimers disease (degenerative disorder)
• Cerebral palsy (motor disorder)
• Depression (mood disorder)
• Epilepsy
• Multiple sclerosis
• Parkinsons disease
• Schizophrenia
• Stroke

20
Animal Testing

• Animal nervous systems similar to Human
• Many neuroscience discoveries were found using
  animal nervous systems.
• Question are experiments on animals necessary?
• Question Is it right?

21
Nerve cells, Action Potentials and Synaptic
Transmission
22
Nervous system

• Nervous system consists of a vast quantity of
  interconnected cells organised in various
  structures.
• Major part in information processing in the
  nervous system play neurons, cells receiving
  information and transmitting it to other cells.
• Cannot separate the neurons metabolic process
  from the process of information processing,
  functional processes

23
Distribution of neurons
Cerebral cortex 12-15x109
Cerebellum 70x109
Spinal cord 1x109
24
The neuron structure

• Neurons share many features of other cells but
  also have some distinct features
• Cell body (soma)
• Contains cytosol fluid in which float cell
  organelles
• Membrane
• Phospholipid bilayer actively regulating
  cell-environment interaction
• Dendrites
• Input
• Axons
• output

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Organelles

• Nucleus
• Contains chromosomes (DNA)
• Involved in hereditary control
• Blueprint
• Rough endoplasmic reticulum
• Contains ribosomes
• Responsible for synthesis, isolation,
  modification, and transportation of proteins
• Smooth endoplasmic reticulum
• Protein 3D folding
• Regulations internal concentration of calcium
• Golgi apparatus
• Protein sorting
• Mitochondria
• Metabolic activities
• Energy production

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Membrane

• Gives identity to the structure which we call a
  cell
• Isolation from external environment
• Protects the cell
• Controlled communication
• Gets rid of waste
• Allows input
• Ion channels
• Open and close selectively to control flow
• Sodium and potassium channels affect membrane
  potential

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Ion channel
Protein ion channel
Phospholipid molecules
28
Axon

• Main information sender
• Thin fibre constant diameter
• Extend for long distances
• Axon collaterals
• Branches to intervene with several other cells
• Presynaptic terminals or boutons
• At end of axon collaterals
• Junction for communication
• Axoplasmic (anterograde) transport
• Delivery of neurotransmitters to presynaptic
  terminals
• Makes possible the interneuron communication

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Dendrites

• Main information receivers of the neuron
• Branching fibres
• Taper away from cell body

30
Cytoskeleton

• The cytoskeleton is a cellular "scaffolding" or
  "skeleton" contained within the cell
• Microtubials
• transport of organelles within the cell
• Neurofillaments
• Microfilaments
• resists tension and maintains cellular shape

31
Neuron Classification

• Main neuron classification
• Morphological
• Dendrites
• Connections
• Axon length
• Chemical
• Neurotransmitter type

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Glia

• Important cells of the nervous system
• They do not convey information over long
  distances
• Exchange chemicals with neighbouring neurons

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Astrocytes

• Astrocytes pass chemicals back and forth between
  neurons and blood and among various neurons in
  an area

Capillary
Astrocyte
34
Schwann cell

• Axon isolation in periphery nervous system
• Myelin sheaths

Axon
Schwann Cell
35
Oligodendrocytes
Axon
Oligodendrocyte

• Axon isolation in central nervous system

Myelin sheath
36
Myelin sheaths
Axon
Myelin sheath
Axon
Node of Ranvier
37
Resting potential

• The membrane maintains readiness for response
• Creates slightly negative resting potential
  (-70mV)
• Difference in voltage across membrane between
  inside and outside of neuron
• Negative due to negatively charged proteins
• Neuron membranes ion channels allow selective
  ions to pass
• Selective permeability maintains electrical
  gradient
• At rest sodium channels tightly shut and
  potassium channels open

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Resting potential

• Sodium potassium pump
• Active transport system
• Uses energy to push 3 sodium ions out and 2
  potassium ions into cell
• Differential concentration gradient
• Na insideoutside 110
• K insideoutside 201
•  
• Electric gradient pushes potassium ions inside
  the cell, whereas the concentration gradient
  pushes them out of the cell.
•  
• Resting potential results as a dynamical balance
  between concentration gradient, electric gradient
  and active transport by the sodium-potassium pump

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Resting potential
Movement of ions
Distribution of ions
Na
Na
Sodium potassium pump
Na
K leaves cell because of concentration gradient
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
Na
K
Na
Na
K
K
K
K
Na
K
K enters cell because of electrical gradient
K
Na
K
K
K
K
Na
Na
Na
Na
Na
Na
Na
Na
K
Na
Na
Na
Na
K
Na
Na
Na
Na
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Net Results

• Steady state 70mV
• Dynamic equilibrium lots of activity to achieve
  this
• erratic stochastic random but a bias a
  propensity for one state sodium closed,
  potassium open

State
Open
Closed
41
Action Potential

• If membrane potential is slightly perturbed it
  quickly returns to the resting potential.
• However if the disturbance (depolarisation) is
  sufficiently large (reaches threshold) an action
  potential starts a massive and rapid
  depolarisation followed by a slight reversal of
  the polarisation.

42
Action Potential

• Action potentials constitute a basis for the
  information encoding by single cells.
• Generation of action potentials or spikes has
  molecular basis, it depends on voltage gated
  channels.
• Action potential is binary all or none
• amplitude does not depend on the level of the
  initial depolarisation which triggered the spike.
• Synaptic responses (axon dendrite join) is not
  binary

43
Action potential

• When the depolarisation reaches a threshold level
• sodium channels start to open very rapidly
• sodium current flows into the cell leading to
  quick further depolarisation.
• At the peak of depolarisation sodium channels
  close
• Making it impossible for sodium to flow into
  cell.
• Meanwhile the potassium channels open more slowly
  and reach peak opening when sodium channels are
  already closing.
• The flow of potassium is in the opposite
  direction and drives the membrane potential down
  (hyperpolarizes it).
• As potassium channels close slower than sodium
  channels, the imbalance of the ion flows leads to
  membrane hyperpolarisation.

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Action potential neuron action
Overshoot
Rate of sodium into neuron
0
Rising phase
Rate of exit of potassium from neuron
Falling phase
-70mV
undershoot
1 msec
1 msec
After hyperpolarisation state refractory period
45
Ion channel states

• main factor affecting state of channels is the
  membrane potential the sodium channel will be
  affected by the membrane potential
• potassium channels 2 states, open and closed
• sodium channels 3 states, open, inactive and
  closed
• (underlining above indicates no ion flow)
• Potassium at rest is slightly open

Sodium
Potassium
Closed
No flow
Inactive
Closed
Open
Open
46
Cybernetic analogy

• Feedback
• Closed loop system
• Common variable is membrane potential
• 2 systems sodium and potassium

Opening of ion channel
Flow of ions
47
Refractory period

• When things calm down, the Sodium/potassium pump
  (working in the background) restores the
  concentrations and therefore the membrane
  potential to resting state.
• This is the refractory period.
• Absolute not going to see any reaction (most of
  sodium channels in a particular state inactive)
  shortly after peak of spike
• Relative depends on the amount of stimulus you
  receive (re sodium ion channels are closed but
  could be opened if action exceeds / undershoots)
  requires higher stimulus due to
  hyperpolarisation

48
Propagation of Action Potentials

• Membrane of a neuron is an active medium - It may
  sustain and propagate the initial membrane
  potential
• Chain reaction
• In an extended segment of the axon
• Nearby action potential related sodium entry
  depolarizes membrane above threshold
• Chain reaction
• Leads to generation of an action potential in a
  neighboring patch

49
Propagation of Action Potentials

• Spikes
• Unidirectional propagation due to refractory
  period
• Depolarisation spreads bidirectionally
• Due to membrane behind current spike being in the
  absolute refractory period, only the membrane in
  front can generate another action potential

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Propagation of Action Potentials
a)
b)
51
Propagation of Action Potentials

• Action potential is slow in unmyelineated axons
  because it depends on diffusion of sodium ions
  (up to 10 m/s)
• In axons with myelin sheath
• Myelin sheath acts like an insulated
• Saltatory conduction between nodes of Ranvier
  (gaps in myelin) speed up propagation up to 120
  m/s
• This is due to there being no sodium channels
  under myelin and so propagation can occur without
  continuous spike regeneration

52
Propagation of Action Potentials
53
Synapse

• Point of communication between two neurons
• Pre-synaptic and postsynaptic neurons do not
  actually touch messages must transmit across
  narrow gap
• Gap between pre- and postsynaptic membrane is
  called a synaptic cleft
• Synaptic transmission takes the form of chemical
  diffusion of neurotransmitters

54
Synapse transmission

• A single stimulation at a synapse produces graded
  potential at the postsynaptic cell rather than a
  full action potential
• Excitatory synapse
• excitatory postsynaptic potentials (EPSP)
  produced
• Sodium gates are opened
• Inhibitory synapse
• Inhibitory postsynaptic potential (IPSP) produced
• Potassium or chloride gates are opened

55
Synapse Transmission

• Synaptic stimulation (graded potentials) on the
  dendritic tree can be integrated in two ways
• Temporal Integration summation of stimuli at
  different times
• Spatial Integration summation of different
  locations

56
Synapse transmission
Synthesis of neurotransmitter and formation of
vesicles
1
Transport of neurotransmitter down axon
2
3
Action potential travels down the axon
Action potential causes calcium to enter, evoking
release of neurotransmitter
4
7
Reuptake of neurotransmitter to be recycled
5
8
Vesicles without transmitter transported back to
cell body
Neurotransmitter attaches to receptor, exciting
or inhibiting postsynaptic neuron
6
Separation of neurotransmitter molecules from
receptor
57
Neurotransmitters

• Some neurotransmitters are produced in cell body
  and are actively transported to the presynaptic
  terminals
• Transport is relatively slow due to neurons
  needing time to replenish larger neurotransmitters

58
Neurotransmitters

• Synaptic transmission is triggered by an action
  potential arriving along the axon terminal
  collateral towards the bouton
• Causes depolarisation of bouton membrane leading
  to opening of the voltage-gated calcium channels
• Calcium flows into presynaptic terminal and
  triggers exocytosis
• Neurotransmitters released into the synaptic
  cleft
• Neurotransmitters diffuse across cleft and are
  attached to receptors on the postsynaptic
  membrane, triggering a response

59
Neurotransmitters

• Each neuron releases the same (limited)
  combination of neuron transmitters from al the
  axon branches
• This increases message complexity
• Neurons can respond to different
  neurotransmitters at different synapses
• There are two types of neurotransmitters
  (dependant on the results of attachment to
  postsynaptic receptors)
• Ionotropic
• Metabotropic

60
Ionotropic

• Ionotropic neurotransmitters attach to receptors
  resulting in opening of certain ion channels
• Effects are rapid and short
• Action localised to immediate vicinity of the
  membrane patch with the receptors
• Examples
• glutamate opens sodium channels (excitatory)
• GABA opens chloride channels (inhibitory)
• Acetylcholine allows sodium ions in (excitatory)

61
Metabotropic

• Metabotropic effects initiate a sequence of
  metabolic reactions
• Slow and longer lasting
• Use second messenger systems
• E.g. cAMP
• Carry messages to areas within a cell
• Open/close ion channels, alter protein synthesis
  or activate a portion of the chromosome
• A metabotropic synapse may affect activity in the
  entire postsynaptic cell (nonlocal effect)

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Anatomy of the nervous system
63
Anatomy of nervous system

• Brain
• Spinal cord
• Hindbrain
• Midbrain
• Forebrain
• Peripheral nervous system
• Somatic conveys information from sense organs
  to CNS and controls voluntary muscles
• Autonomic nervous system organs and involuntary
  muscles
• Sympathic expenditure of energy, flight or
  fight
• Parasympathic conserving energy and vegative
  functioning

64
Nervous system
Brain
Corpus Callosum
Cerebral Cortext
Spinal cord
Thalamus
Hypothalamus
Pituitary gland
Pons
Cerebellum
Medulla
Peripheral nervous system Somatic
(blue) Autonomic (red)
65
Autonomic nervous system
66
Anterior plane
Sagittal plane
Coronal plane
67
Anatomical directions
68
Spinal cord

• Part of the CNS within spinal column
• Responsible for communication with muscles and
  sensory organs below head
• Each segment has a pair of nerves on both sides
• Dorsal roots enter spinal cord carrying sensory
  information. Sensory neurons bodies are located
  in the dorsal root ganglia.
• Ventral roots exit spinal cord and carry motor
  information to the muscles
• Grey matter consists of densely packed cell
  bodies and dendrites
• White matter consists of myelineated axons

69
Spinal Cord
White matter
Grey matter
Sensory nerve
Central canal
Dorsal root ganglion
Dorsal
Motor Nerve
Ventral
70
Brain Stem
Midbrain
Forebrain
Olfactory bulb
Hindbrain
Optic nerve
Figure 4.7 three major divisions of the
vertebrate brain In a fish brain, as shown here,
the forebrain, midbrain, and hind brain are
clearly visible as separate bulges. In adult
mammals the forebrain grows so large that it
surrounds the entire midbrain and part of the
hindbrain
71
Brain Stem

• Consisting of parts of
• Hindbrain
• Midbrain
• Some structures of forebrain
• Hindbrain
• Medula
• Extension of spinal cord involuntary reflexes
• Pons
• Reticular formation motor areas of spinal cord
  and controls arousal and attention by projecting
  output to the cerebral cortex
• Raphe system projects to the forebrain and
  modulates the brains response readiness to
  stimuli.
• Cerebellum
• Lots of neurons, more than forebrain
• Control of movement, balance and coordination,
  shifting attention between auditory and visual
  stimuli, timing

72
Brain stem

• Midbrain contains pathways between the forebrain
  and the hindbrain or the spinal cord
• Consists of
• Tactum
• Tegmentum
• Supperior colliculus
• Substantia nigra (dopaminergic system)

73
Brain stem

• Forebrain largest part of the brain in mammals
• It is divided into two hemispheres connected by
  corpus callosum and anteriror commisure
• Contains
• Cerebral cortex
• Thalamus
• Limbic system
• Basal ganglia

74
Forebrain

• Limbic system set of structures around the
  brain stem
• Olfactory bulb
• Hypothalamus
• Motivated behaviours (e.g. feeding, drinking,
  temperature regulation, sexual behaviour or
  fighting)
• Pituitary gland
• Endocrine gland responsible for the synthesis and
  release of hormones
• Hippocampus
• Stores certain kinds of memories and involved in
  memory consolidation
• Amygdala
• Expression of fear as well as aggressive behavoir
• Cingulate gyrus

75
Forebrain
Thalamus
Hypothalamus
76
Forebrain

• Thalamus
• Relay station of sensory information between
  sensorium and cerebral cortex
• Olfactory system not handled by Thalamus
  olfactory bulbs
• Consists of many nuclei group of neurons to
  achieve some function
• Some receive input from one sensory system (e.g.
  vision) and project to a single cortical area
• Others have multiple connections with several
  sensory systems, other nuclei and many cortical
  areas

77
Forebrain
78
Forebrain

• Basal ganglia
• Makes connections to the frontal cortex
• Involved in several functions
• Contains
• Caudate nucleus
• Putamen
• Globus pallidus
• Deterioration causes
• Impaired movement
• Depression
• Memory and reasoning deficits
• Attentional disorders

79
Forebrain
80
Forebrain
81
Forebrain
82
Cerebral cortex

• External layer of grey matter
• Contains neuron bodies
• Neurons communicate with other cortical neurons
• Sending axons forming white matter of the
  forebrain underneath the cortex
• Laminar structure
• 6 layers of neurons
• Neurons in cortex are arranged in columns
• Cells in the same column have similar properties
• Most of cortical areas are involved in many
  different functions but to varying degrees of
  freedom.

83
Cerebral Cortex
84
Cerebral Cortex
85
Cerebral Cortex
86
Cerebral Cortex

• 4 lobes
• Occipital
• Located at back main target for thalamic
  projects with visual information
• Contains primary visual cortex perception and
  imagery
• Parietal
• Contains somatosensory cortex somatosensory
  representation of the body (damage leads to
  neglect cannot control or sense a particular
  body part)
• Temporal
• Auditory information involved in hearing and
  spoken language understanding as well as vision,
  emotional and motivational behaviours
• Frontal
• Primary motor cortex fine movement control
• Prefrontal cortex working memory, memories of
  current stimulus, movement planning, regulation
  of emotional expression

87
Cerebral Cortex
88
Binding problem

• The brain is neither
• a collection of completely independent subsystems
  each with a very specialised function
• or a homogenous system with all its parts
  contributing equally to the functionality of the
  whole
• If there is some degree of specialisation and
  different sensory information is processed in
  different brain regions then how is it put back
  together into a coherent unitary experience of
  things?

89
Binding problem

• Fundamental problem with deep philosophical
  implications
• There is no homunculus which would collect and
  interpret all the information processed by
  different regions
• There is no single area in the brain where it
  all comes together

90
Binding Problem

• Proposed solutions
• Synchrony of activity in different brain areas
  (gamma waves) may be responsible for binding of
  information
• Information is encoded (mean rate of neuron
  firing) in the temporal structure of massages and
  this richer information may allow for binding.

91
Plasticity of the Brain

• Development and change

92
Development of the vertebrate Brain

• In vertebrate embryos the CNS starts as a fluid
  filled tube
• Fluid is cerebrospinal fluid (CSF)
• Proliferation of neurons
• Cells lining the ventricles divide
• Cells that become neurons glia migrate to their
  target regions in the brain
• Initially they are just like other stem cells,
  but they begin to differentiate and develop first
  axon and later dendrites
• Location of neurons affects their shape and
  properties
• The glia cells start to wrap around axons of some
  neurons create myelin sheath around them
  (myelination)
• Myelin forms in humans in the spinal cord, then
  the hindbrain, midbrain, and in the forebrain
• Maturation of the brain is accompanied by both
  maturation of neurons as well as by the
  development of brain areas.

93
Development of the vertebrate Brain
94
Development of the vertebrate Brain
95
Development of the vertebrate Brain

• Initially the number of neurons is much greater
  than in later stages.
• Neurons make contacts with neurons sending nerve
  growth factor (NGF) and other neurotophins
• Only neurons receiving neurotrophins survive
• If insufficient neurotrophins are received, its
  axon degenerates and the cell dies (apoptosis
  programmed cell death)

96
Development of the vertebrate Brain
97
Axon Pathfinding

• During connectivity development, axons navigate
  to specific targets
• Pathfinding is very precise and ensures the
  nervous system can send signals to the right
  targets
• Chemical navigation
• Axons follow different chemicals over different
  parts of their pathway
• Become sensitive and insensitive to certain
  chemicals as they pass through the regions
• In the target area the amount of neurotrophins
  determines the extent of axonal branching
• Attach to target area by arraying over chemical
  gradients

98
Axon Pathfinding
99
Axon Pathfinding

• When the target is reached, the axon form many
  synapses on the target neuron
• With time some of the synapses are removed
• General principle axonal competition
• Neural Darwinism natural selection where more
  successful synapses are retained at the expense
  of less successful ones

100
Experience and dendritic branching

• Development of connectivity in the brain is
  dependent on the experience of the individual
• Enriched environments enhance axonal sprouting
  and dendrite branching
• In humans, the extent of education correlates
  positively with the increased dendritic branching

101
Generation of new neurons

• Traditionally believed that neurons do not
  regenerate in the adult brain
• Recent evidence suggest that this is not entirely
  correct
• Immature cells in the nose divide and replace
  olfactory receptors
• Stem cells (undifferentiated cells) lining the
  interior of ventricles generate cells migrating
  to the olfactory bulb replacing the neurons and
  glia
• Also new cells develop in the hippocampus and
  some parts of the cortex, although their
  functional role is unknown

102
Role of action potential in development
103
Brain development

• Although there are many factors affecting the
  brain development they seem to affect equally
  different brain areas.
• In mammals the size of the brain correlates very
  well with the size of its major components

104
Impediment of Brain Development

• Genetic abnormalities
• Malnutrition
• Chemical environment
• Foetal alcohol syndrome
• Exposure to alcohol during prenatal development
• May result in
• Decreased alertness
• Hyperactivity
• Mental retardation
• Motor problems
• Hearing defects
• Facial abnormalities
• Neurons in affected individuals have shorter
  dendrites with few branches. In adulthood, they
  are more susceptible to alcoholism, drug
  addiction, depression

105
Brain damage

• Causes
• Strong or repeated blows to the head (e.g.
  boxing)
• Strokes or cerebrovascular events (occurs mostly
  in older brains and kills neurons by
  overstimulation)

106
Strokes

• Neurons die in two stages
• In the immediate vicinity of the stroke, the
  neurons die quickly
• In the penumbra (region surrounding immediate
  damage) may did in next few days/weeks after the
  stroke
• Two stroke types
• Ischemia results from an obstruction of an
  artery by a blood clot. Afterwards the penumbra
  dies by lack of oxygen and glucose
• Haemorrhage rupture of an artery. Penumbra is
  flooded by an excess of oxygen, calcium etc

107
Strokes

• Both stroke types share a number of similar
  mechanisms leading to extensive damage.
• The waste products from dead and dying cells
  flood penumbra. Due to breaking of bloodbrain
  barrier forms oedema (accumulation of fluid).
• Lower levels of energy lead to slowing down of
  sodium-potassium pump and consequently to
  accumulation of potassium outside neurons.
• This causes glia to dump their stores of
  neurotransmitters including glutamate
  (excitatory) causing over-excitation of neurons.
• This leads to accumulation of positive ions (Na,
  Ca, Zn) in neurons, which is likely to
  trigger their death. In the final stages glia
  cells remove waste and dead neurons.

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Stroke
109
Recovery

• Recovery depends on
• learned changes in behaviour using remaining
  skills
• Increase of activity in neurons remote from the
  site of injury, which became less active due to
  decreased input (diaschisis) caused by the damage
• Diaschisis treaded with
• Stimulant drugs e.g. amphetamine, combined with
  the physical therapy
• Physical therapy

110
Recovery

• Recovery Mechanisms in the nervous system
• Axonal regrowth in mammals axon do not
  regenerate far due to growth-inhibiting chemicals
  produced by central myelin
• Sprouting axons take over vacant synapses after
  death of a neighbouring axon. Neurons may become
  responsive to other axons if axons innervating it
  become inactive or die.

111
Recovery
112
Recovery

• Supersensitivity
• Denervation supersenitivity heightened
  sensitivity of postsynaptic neuron to a
  neurotransmitter after destruction of an incoming
  axon
• Disuse supersensitivity increased sensitivity
  in response to inaction by an incomming action
• Supersensitivity results from increased number of
  receptors on the postsynaptic neuron and from
  their increased effectiveness

113
Sensory changes

• The brain is able to reorganise its sensory
  representations in response to permanent changes
  in incoming information
• Example limb amputation
• Sensory neurons from limb no longer contact brain
• Areas reorganise
• Areas representing parts/limbs are not static but
  are in dynamic equilibrium due to cell
  competition and constant influx of information.
• Amputation terminates influx of sensory
  information leading to reorganisation of
  somatosensory cortical areas, where neighbouring
  areas invade the area correspond to the amputated
  limb.
• Phantom limb areas responsible for limb are
  reassigned

114
Sensory Changes
115
Sensory changes
116
Vision
117
From senses to sensations

• Senses provide us with information about the
  environment
• Exchange of information involves the exchange of
  energy between the environment and the organism
• Three stages for sensation to occur
• Reception absorption of energy by receptors
• Transduction conversion of physical energy into
  electrophysical pattern in neurons
• Coding creation of correspondence between the
  stimulus and some brain activity (e.g. mean rate
  coding, spike interval coding)
• One of the fundamental and as yet unresolved
  problems in neuroscience is the labelled lines
  problem or colours of waves
• We do not now how the action potentials
  propagated along particular nerves somehow code
  the same kind of information to the brain

118
The Eye

• Reception and transduction of visual information
• Oval shape
• Light progression
• Enters through the pupil
• Concentrated by the lenses
• Travels through the vitreous humour
• Hits the Retina

119
Retina

• Layer of photoreceptors
• Macula
• Area of heightened acuity
• 3-5mm area
• Fovea
• central part of macula and has highest density of
  photoreceptors
• Receptors have an almost one to one connection
  pattern with postsynaptic neurons (bipolar cells)
• Periphery
• Each receptor has higher coverage
• Sums the inputs lower acuity but higher
  sensitivity to week stimulus (e.g. faint light)

120
Retina

• inside out organisation
• Light has to pas through layers of axons, cells
  and blood vessels in order to reach the
  photoreceptors
• The receptors make connections onto the bipolar
  cells, which are connected to the ganglion
• Axons of the ganglion cells bundle together and
  form an optic nerve
• The blind spot does not contain any receptors and
  is completely insensitive to light. It is the
  place where the optic nerve leaves

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The Eye
122
The Eye
123
Receptors

• There are two types of receptors
• Rods
• 120 million
• Increases towards periphery
• Very sensitive responds to faint light (even to
  single photons)
• Cones
• 6 million
• Concentrated mainly in the fovea and macula
• Different types of cones each broadly tuned to
  different wave lengths of light
• Involved in colour vision

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Receptors

• Photopigments
• Chemicals contain in photoreceptors
• Absorb photons and release energy
• Stimulation of photopigments leads to activation
  of 2nd massagers responsible for closing of
  sodium channels resulting in membrane
  hyperpolarisation
• Inhibition of photoreceptors causes inhibition of
  synapses onto bipolar cells
• This results in excitation of bipolar cells
• Light stimulation of receptors leads to
  activation of neurons and sending electrical
  signals down the optic nerve

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Receptors
126
Colour Vision

• Complex patterns of responses by many neurons and
  comparison of responses across different cone
  types
• Although most vertebrates have some cones in
  their retina, only those with different cone
  types can discriminate colours (e.g. rats cannot
  they only have one cone type)

127
Theories of Colour Vision

• If we assume that neurons encode information in
  their firing frequency then only one property can
  be encoded at once (e.g. luminance or colour).
  Patterns or activity across different neurons
  must be responsible.
• There are three main theories
• Trichomatic theory (Young and Helmholtz)
• Opponent process theory
• Retinex theory (Land)

128
Theories of Colour Vision

• Trichomatic theory (Young and Helmholtz)
• A given wavelength of light stimulates a
  distinctive ratio of responses of 3 types of
  cones
• Although stronger light results in stronger
  responses, the ratio remains largely the same
• Can explain encoding of both brightness and
  colour at the same time
• Predicted existence of difference cone types
• It does have problems explaining negative colour
  afterimage

129
Theories of Colour Vision

• Opponent process theory
• Colours are perceived on continuous scales,
  red-green, yellow-blue, white-black
• Emphasised involvement of other cells than
  receptors
• Neurons other than receptors increase activity in
  response to one colour and decrease activity to
  indicate the opposite colour
• Suggests specific neural connectivity between
  cells in retina
• It cannot account for colour constancy the
  ability to recognise correctly colours in varying
  lighting conditions it requires comparison of
  colours across different areas.

130
Theories of Colour Vision
131
Theories of Colour Vision

• Retinex theory (Land)
• Can explain colour constancy
• Cortex compares the responses of different parts
  of the retina to determine the brightness and
  colour of each area
• Responsibility for colour perception is in the
  cortex

132
Mammalian visual system

• Receptors make contacts onto the bipolar cells
• Bipolar cells make contact with amacrine and
  ganglion cells
• Ganglion cells axons form an optic nerve leaving
  eyes
• Optic nerves from both eyes meet at the optic
  chiasm, where some of the axons from each eye
  cross to the other side of the brain (50 in
  humans)

133
Mammalian visual system

• Majority of axons then enter lateral geniculate
  nucleus
• Part of thalamus involved in processing of visual
  information
• LGN makes projections to the visual cortex in the
  occipital lobe
• Small number of the axons goes to another
  structure called suprachiasmatic colliculus and
  few to the part of hypothalamus responsible for
  the wake-sleep cycle.

134
Mammalian visual system
135
Mammalian visual system
136
Mechanisms of processing

• Receptive field
• Part of the visual field to which a neuron
  responds
• The receptive field of a receptor is the area in
  space from which light arrives
• The receptive field of a ganglion cell will be a
  combination of the receptive fields of receptors
  it is connected to.
• The receptive field becomes more complex in
  consecutive stages of the visual system

137
Mechanisms of processing

• Lateral inhibition
• Contrast enhancement
• Stimulation in one area of the retina inhibits
  the responses in the neighbouring areas
• Visual pathways
• Organisation of neurons
• Starts at the level of retinal ganglion

138
Mechanisms of processing

• Parvocelluar
• Neurons concentrated around fovea
• They are smaller and have smaller receptive
  fields
• Involved in processing colour and fine detail
• Magnocellular
• Neurons evenly distributed
• Respond to depth, movement and large patterns
• Two neuron types make connection with the
  correspond types of neurons in the LGN. Thus both
  pathways remain distinct

139
Cerebral Cortex

• LGN makes projects to the primary visual cortex
  (V1)
• the first stage of processing
• V1 sends projects to V2
• Further stages of the visual processing
• Makes feedback connections to V1

140
Cerebral cortex

• The two pathways originating in the retina form
  three pathways in the cortex
• The mostly magnocellular pathway branches into
  the ventral part involved in motion perception
  and the dorsal part involved in integration of
  vision and action
• The mixed magnocellular and parvocellular pathway
  is responsive to colour and brightness
• The parvocellular pathway is involved in fine
  shape analysis

141
Cerebral cortex

• Ventral stream
• Mixed m/p path mostly p path
• Visual paths in the temporal cortex
• what pathway
• Object identification
• Dorsal stream
• Magnocelluar path entering parietal cortex
• where pathway
• Shape perception

142
Shape analysis pathway

• Cells in V1 and V2 are classified according to
  their receptive field type
• Simple cells
• Mostly in the primary visual cortex
• Fixed excitatory and inhibitory parts in their
  receptive fields
• Complex cells
• Found in V1 and V2
• No fixed excitatory/inhibitory zones
• Respond to preferred stimulus orientation
  regardless of the position within the receptive
  field
• Cells in the visual cortex are grouped in columns
  in which cells with similar properties cluster
  together

143
Shape analysis pathway

• V1 and V2 feature detectors or frequency filters?
• Hubel and Wiesel classification of cells suggest
  that cells might be simply feature detectors
• There is however evidence that they may be
  responsive to gratings rather than to bars
• This would mean that cells are frequency filters
  tuned to different spatial frequencies and the
  visual system performs some form of Fourier
  analysis
• This is still open to debate
• Cells in higher order systems (e.g. inferior
  temporal cortex) have big receptor fields
• Provides no additional positional information but
  seem able to respond to specific shapes (shape
  detectors)

144
Disorders of shape recognition

• Certain damages to the brain results in
  impairments of visual perception
• Visual agnosia
• Inability to recognise objects
• Prosopagnosia
• Inability to recognise faces but able to
  recognise other objects

145
Colour perception pathway

• Colour perception pathway involves the
  parvocellular path
• Cells in V1 (sensitive to the colour) form blobs
• Neurons from V1 blobs innervate V2, V4, and
  posterior inferior temporal cortex
• Particularly V4 was implicated in colour
  constancy perception

146
Motion and depth pathways

• Areas involved in motion perception
• Magnocellular pathway
• MT (V5)
• MST (cells are sensitive to the motion velocity)
• Patients with certain brain damage suffer from
  motion blindness
• Intact object recognition
• Cannot determine object movement or its speed and
  direction of movement

147
Hearing, Somatosensation, Chemical Senses
148
Hearing

• Sound
• Amplitude intensity perception loudness
• Frequency perception pitch
• Structure of the Ear
• Pitch perception
• Localisation of sounds
• Vestibular system

149
Structure of the Ear

• Outer ear
• Pinna
• External auditory canal
• Middle ear
• Eardrum
• Hammer, anvil and stirrup
• Inner ear
• Oval window
• Cochlea 3 fluid filled tunnels, hair cells lie
  between the basilar membrane and tectorial
  membrane

150
Structure of the Ear

• When sound waves strike the tympanic membrane
• They cause it vibrate three tiny bones the
  hammer, anvil and stirrup that convert the
  sound waves into stronger vibrations in the
  fluid-filled cochlea
• Thos vibrates displace the hair cells along the
  basilar membrane in the cochlea
• A cross section through the cochlear. The array
  of hair cells in the cochlea is known as the
  organ of Corti
• Close-up of the hair cells

151
Auditory Cortex

• Cells tuned to different tone frequencies
• Cells responding to a given tone cluster together
  (tonoptic maps)
• Ventral path (type of sound)
• Dorsal path (localisation of sound)

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Auditory Cortex
153
Pitch Perception

• Frequency theory
• Basilar membrane vibrates in sync with a sound
  causing the auditory nerve axons to produce
  action potentials with the same frequency
• Place theory
• Each area of basila membrane is tuned to a
  specific frequency and vibrates if that frequency
  is present

154
Pitch perception

• Currant theory combination of the two
• Low frequency sounds frequency of action
  potentials in the auditory system
• Intermediate frequencies volleys of responses
  across many receptors can lead to the encoding of
  sounds of frequency of up to ca. 5000Hz in the
  who auditory nerve even though no individual axon
  can fire with that frequency
• High frequency sounds area of greatest response
  along the basilar membrane due to location of
  peaks of the travelling wave in the basilar
  membrane

155
Pitch perception
156
Localisation of sounds

• High frequency
• Loudness difference between ears
• Low frequency
• Differences in phase

157
Vestibular System

• Vestibular organ
• adjacent to cochlea
• Detects position and acceleration of the head
• Consists of 2 otholit organs and three
  semicircular canals (in three planes) filled with
  a jellylike substance and lined with hair cells
• Head tilts are detected by the otholit organs
  (otholits calcium carbonate particles push
  against the hair cells)
• Acceleration is detected by the canals

158
Vestibular System
159
Somatosensation

• Many senses in one
• Depends on a number of receptors sensitive to
  different kinds of skin and internal tissue
  stimulation
• Each receptor contributing in some degree to many
  somatosensory experiences

160
Somatosensation
161
Somatosensation
162
Pain

• Function
• Trasmitted by axons releasing glutamate for
  moderately painful stimuli and a combination of
  glutamate and substance P for strong pain
• Many kinds of pain are dependent on unmyelinated
  or thinly myelinated axons carrying information
  to the spinal cord and releasing there a
  cotrasmitter substance P
• A chemical capsaicin (jalapenos) produces a
  transient pain by enhancing release of substance
  P and stimulation of the moderate heat receptors.
  This pain is followed by the relative
  insensitivity due to need for restoring the
  neuronal supply of substance P and weakening of
  heat receptors.

163
Pain relief

• A harmful stimulus may evoke varying feeling of
  pain depending on the other current and recent
  stimulus
• Experience of pain is related to the activity of
  cingulate cortex (emotional response) and
  somatosensory cortex
• Gate theory some areas of the spinal cord
  receive stimulus from pain receptors and from
  other receptors in the skin as well as axons
  descending from the brain these stimuli can
  close the gates and block the trasmission of
  pain.
• Opioid Mechanisms opioids bind to the receptors
  concentrated in the same brain areas where
  substance P is concentrated they reduce pain
  because they attach to the endorphin receptors

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165
Pain relief

• Analgesia some painful stimuli activates
  neurons releasing endorphins in the
  periaqueductal area
• Axons from exited cells in medulla and the
  periqueductal area send messages to the spinal
  cord and block release of substance P
• Endorphins
• Act on small diameter pain fibres they relieve
  slow dull pain ineffective for sharp strong pain
• Release of the endorphins (decrease of pain
  sensitivity) can be triggered by both pleasant
  and unpleasant experiences

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167
Pain relief

• Both morphine and pain transiently impair the
  immune system
• Pain impairs it more so the net effect of
  relieving pain with morphine is enhancement of
  the immune system
• Tissue damage activates the immune system, which
  released chemicals (e.g. histamine) repairing the
  damage but also makes the pain receptors over
  responsive to further pain or even a mild stimulus

168
Taste

• Sensory information can be coded using labelled
  lines or across fibre coding
• Taste receptors
• modified skin cells (life cycle of 10-14 days)
• In taste buds located in papillae on the tongue
• 5 kinds of taste receptors
• Salty receptors detect sodium ions crossing the
  membrane
• Sour receptors respond to the stimulus by
  blocking potassium channels
• Sweet, bitter and umani receptors response
  similar to the metabotropic receptors,via a
  second messengers system

169
Taste
170
Taste