1. BIOLOGICAL PSYCHOLOGY I
Giorgia Silani
giorgia.silani@sissa.it

2. STRUCTURE OF THE COURSE: WHEN
• Thursday 21/10/2010: 12 -17
• Friday 22/10/2010: 10-15
• Thursday 11/11/2010: 12 -17
• Friday 12/11/2010: 10-15
• Thursday 02/12/2010: 12 -17
• Friday 03/12/2010: 10-15

3. STRUCTURE OF THE COURSE: HOW
• 50 minutes: Frontal Lecture…but open to discussion.
•Feel free to ask questions!
• 10 minutes BREAK: you and me to recover a bit!
• After each topic, some practical exercise…good training for the final
exam

4. STRUCTURE OF THE COURSE: WHAT
• Chapter 01: Historical review .
• Chapter 02: Cell biology of neurons
• Chapter 03 - 04: Physiology of neural membrane
• Chapter 05 - 06: Communication between neurons
• Chapter 07: Anatomy of the nervous system
• Chapter 08: Smell and Taste
• Chapter 09 - 10: Visual system
• Chapter 11: Auditory system
• Chapter 12: Somatic sensory system
• Chapter 13 - 14: Motor systems
Textbook: Bear, Connors, Paradiso “Neuroscience,
exploring the brain – 3rd edition”
Additional material on the webpage of the course
Take home message…a lot of stuff to do.

5. STRUCTURE OF THE COURSE: WHO
Torino, Italy Milano, Italy London, UK
Trieste, Italy
Zurich, Switzerland

6. LET’S START

7. NEUROSCIENCE:
PAST, PRESENT, AND FUTURE

8. THE ORIGINS OF NEUROSCIENCE
Neuroscience is the scientific study of the nervous
system.
Relatively young term (Society for Neuroscience 1969)
..but curiosity about the brain and how it works is old as
much as the mankind itself

9. 7000 B.C. ... long time ago
• Prehistoric ancestors
– Brain vital to life
• Skull surgeries
– Evidence: Trepanation
– Skulls show signs of healing

10. 5000 B.C. ... Ancient Egypt
Heart: Seat of soul and memory (not the head)
Mummification process
Canopic Jars were used to hold the organs of the dead after they were
embalmed.
The four organs housed by the jars were the lungs, the stomach, the liver
and the intestines.
Egyptians held no regard for the brain, which was discarded.
The heart (scarab) was left inside the body, to be judged in the afterlife

11. 500 B.C. ... Ancient Greece
Hippocrates (460 -379 B.C.)
• Brain: Involved in sensation;
• Seat of intelligence
Aristotle (384 -322 B.C.)
• Heart: centre of intellect;
• Brain: Radiator for the cooling
of the blood

12. A.D. ... Roman Empire
Galen (130 -200 A.D.)
Correlation between structure and function
• Cerebrum: soft = sensations
• Cerebellum: hard= movements
• Ventricles: contains fluids which
movements to or from regulate perception
and actions

13. From Reinassance to the XIX Century
The Renaissance
Fluid-mechanical theory of brain function
Philosophical mind-brain distinction
Descartes (1596-1650)
The Seventeenth and Eighteenth Centuries
Gray matter and white matter observation
Basic anatomical subdivisions of PNS and CNS
Identifications of gyri, sulci, and fissures
Beginning of the Nineteenth Century
Nerve as wires, understanding of electrical phenomena,
brain can generate electricity
Studies of Charles Bell and Francois Magendie on ventral
and dorsal roots of the nerves

14. the XIX Century
Localization of Function in the Brain
.
If spinal roots carry differential functional information then
different parts of the brain are specialized to process this
information
1809 - Phrenology
Franz Joseph Gall
1823 - Experimental ablation method
Marie-Jean-Pierre Flourens
1861 – Lesioned patients
Paul Broca

15. the XIX Century
Cerebral localization in animals Neuron as the basic
Nervous systems of different
function of the brain
species may share common
mechanisms

16. Neuroscience today
Levels of Analysis
Molecular (i.e. neurotransmitter, enzymes etc.)
Cellular (i.e. types of neurons and their properties)
Systems (i.e. visual, auditory etc.)
Behavioral (from networks to behaviors)
Cognitive ( from brain to mind, i.e. consciousness)

17. Neuroscientists

18. The cost of ignorance

19. NEURONS AND GLIA

20. CELLS IN THE NERVOUS SYSTEM
Glia Neurons
Process information
Insulates, supports,
Sense environmental changes
and nourishes
Communicate changes to other neurons
neurons
Command body response

21. THE NEURON DOCTRINE
Cells are in the range of 0.01 – 0.05 mm of diameter
Need for techniques that allow to see such small structures
Histology
Microscopic study of tissue structure
The Nissl Stain (late XIX century)
Colors selectively only part of the cell (Nissl body)
Facilitates the study of cytoarchitecture in the CNS
Differentiation between neuron and glia
The Golgi Stain (1873)
Revealed the entire structure of the neuron

22. THE NEURON DOCTRINE

23. THE NEURON DOCTRINE
Camillo Golgi’s reticular theory
Neurites of different cells are fused together to form a continuous reticulum, a
network (like blood circulation)
Santiago Ramon y Cajal’s neuron doctrine
Neuron are not continuous one another but communicate by contact
Shared the 1906 Nobel Prize in
Physiology or Medicine

24. THE NEURON
Neuronal membrane
separate the inside from the outside
The Soma
Cytosol: Watery fluid inside the cell
Organelles: Membrane-enclosed
structures within the soma
Nucleus
Rough Endoplasmatic Reticulum,
Smooth Endoplasmatic Reticulum,
Golgi Apparatus
Mitochondria
Cytoplasm: Contents within a cell
membrane (e.g., organelles, excluding
the nucleus)

25. THE NUCLEUS
Contains chromosomes that have the
genetic material (DNA)
Genes: segment of DNA
Gene expression: reading of DNA in order
to synthesize proteins
Protein synthesis happen in the cytoplasm
RNA is the messenger that carry the
information contained in the DNA to the
cytoplasm

26. THE NUCLEUS
The enzyme RNA polymerase binds to the promoter of the gene in order to initiate
transcription
Exons: coding regions
Introns: non –coding regions
In the cytoplasm mRNA transcript
is used to assemble proteins
from amino acids
DNA
transcription
mRNA
translation
Proteins

27. ROUGH ENDOPLASMATIC RETICULUM
Major site for protein synthesis
Contains ribosomes attached to the
ER and free ribosomes
Cytosol Membrane

28. SMOOTH ER and GOLGI APPARATUS
Sites for preparing/sorting proteins for delivery to different cell regions (trafficking)
and regulating substances

29. THE MITOCHONDRION
Site of cellular respiration (inhale and
exhale)
Pyruvic acid and O2, trough the Krebs
cycle are transformed in ATP and CO2
1 Pyruvic acid = 17 ATP
ATP- cell’s energy source (by breakdown
of ATP in ADP)

30. THE NEURONAL MEMBRANE
Barrier that encloses cytoplasm
~5 nm thick
Protein concentration in membrane varies
Structure of discrete membrane regions influences neuronal
function

31. THE CYTOSKELETON
Not static
Internal scaffolding of neuronal membrane
Three “bones”
Microtubules
Microfilaments
Neurofilaments
Microtubules
Big and run longitudinally along the neuron.
Microfilaments
Same size of the membrane. Role in changing cell
shape
Neurofilaments
Mediam size. Structurally very strong

32. THE AXON
The Axon is specialized for the transfer
information over long distances
Axon hillock (beginning)
Axon proper (middle)
Axon terminal (end)
Differences between axon and soma
ER does not extend into axon
(This means no protein synthesis there)
Protein composition: Unique
Variable diameter and length

33. THE SYNAPSE
The axon terminal is the site of contact with
another neuron or cell (synapse) and
transfer of information (synaptic
transmission)
In the Axon Terminal there are no
microtubules
Presence of synaptic vesicles (contain
neurotransmitter)
Abundance of membrane proteins post
synapsis)
Large number of mitochondria

34. THE AXOPLASMIC TRANSPORT
Allows the transport of the proteins
synthesized in the soma to the axon
terminal
Anterograde (soma to terminal):
could be fast (1000mm per day) or
slow (1-10 mm per day). Legs are
Kinesin
Retrograde (terminal to soma)
transport: feedback information.
Legs are dynein

35. THE DENDRITE
“Antennae” of neurons
All the dendrites of a neuron are called dendritic tree
Dendritic spines
Postsynaptic: receives signals from axon terminal by using protein
molecules called receptors that detect neurotransmitters in the synaptic
cleft

36. CLASSIFICATION OF NEURONS
Classification Based on the Number of Neurites
Single neurite
Unipolar
Two or more neurites
Bipolar- two
Multipolar- more than two
Classification Based on Dendritic and Somatic Morphologies
Stellate cells (star-shaped) and pyramidal cells (pyramid-
shaped)
Spiny or aspinous

37. CLASSIFICATION OF NEURONS
Further Classification
By connections within the CNS
Primary sensory neurons, motor neurons, interneurons
Based on axonal length
Golgi Type I - long axon, projection neurons
Golgi Type II - short axon, local circuit neurons
Based on neurotransmitter type
e.g., – Cholinergic = Acetycholine at synapses

38. GLIA
Mainly supports neuronal functions
Astrocytes
Most numerous glia in the brain
Fill spaces between neurons (Influence
neurite growth)
Regulate the chemical context of the
external environment of the neurons
Myelinating Glia
Oligodendroglia (in CNS) and Schwann
cells (in PNS) insulate axons
Node of Ranvier: region where the
axonal membrane is exposed

39. THE NEURAL MEMBRANE
AT REST

40. ELECTRICAL PROPERTIES
Simple reflex : information needs to be quickly transmitted to the CNS and back
Information is transmitted through action potentials (change in the electrical properties of the
membrane)
Cells able to generate an AP have excitable membrane
At rest, these cells have a inside negative electrical charge (resting membrane potential) that
become positive during the AP

41. CYTOSOLIC AND EXTRACELLULAR FLUID
Water is the key ingredient in intracellular and extracellular fluid
Key feature – uneven distribution of electrical charge (O has a net negative
charge)
Ions are atoms or molecules with a net electrical charge dissolved in the water
Salz for example is a crystal of Sodium (Na+) and Chloride (Cl-)
Monovalent Ion: Difference between protons and electrons =1,
Divalent Ion: Difference between protons and electrons =2,
cation (+), anion (-)
When the crystal breaks down spheres of
hydration -layer of water are attracted to the ion
The orientation of the water molecules is
determined by the valence of the ion

42. IONS INVOLVED IN CELLULAR PHYSIOLOGY
Sodium Calcium
+ 2+
Potassium Chloride
+
-

43. THE PHOSPHOLIPID MEMBRANE
Hydrophilic: Dissolve in water due to uneven electrical charge (e.g., salt,
proteins, carbohydrates)
Hydrophobic: Does not dissolve in water due to even electrical charge (e.g., oil,
lipids in general)
The Phospholipid Bilayer
Hydrophilic
Hydrophobic
Resting and Action potentials depend on special proteins that are inserted in the
membrane

44. THE PROTEIN
Proteins are molecules assembled by combination of different amino acids (20 types)
Central alpha
carbon
R group
Amino group Carboxyl group

45. THE PROTEIN STRUCTURE
Peptide bond
Primary
Tertiary
Secondary
Quaternary

46. CHANNEL PROTEINS
Ion Channels
They form a pore through the membrane that hydrophilic
is ion selective
They can be opened and closed (gated)
by changing in the local microenvironment
of the membrane
hydrophobic
Ion Pumps
Formed by membrane spanning proteins
Uses energy from ATP breakdown
Neuronal signaling

47. THE MOVEMENT OF IONS
Diffusion: movement of ion due to concentration levels
Dissolved ions tend to distribute evenly by following down concentration gradient
Concentration gradient = difference of concentration of an ion across the membrane
Electricity
Electrical current (I, measured in Amperes) represents ion movement.
It’s regulated by
1) electrical conductance (g, measured in Siemens) or electrical
resistance (R, measured in Ω): ability (or inability) of an electrical
charge to migrate from one point to another
2) electrical potential (V, measured in volts): difference in charge
between cathode and anode

48. THE MOVEMENT OF IONS
Electrical current flows across the membrane by
Ohm’s law relationship
I =gV or I =V/R
Membrane potential: Voltage across the
neuronal membrane.
The resting potential is typically -65 mV
…let’ see why…

49. EQUILIBRIUM POTENTIAL
Example 1
Equilibrium is reached when
diffusional and electrical
Example 2 forces are equal and opposite
(equilibrium potential, Eion)

50. MEMBRANE POTENTIAL
In the membrane ions have different concentration between inside and outside,
and this gradient is established by action of ionic pumps, that use energy in
order to move ions against concentration forces
Membrane permeability determines membrane resting and action potentials

51. MEMBRANE POTENTIAL
Membrane permeability determines membrane resting and action potentials
Membrane rest potential is determined by the higher number of K vs. Na channels
open (resting potential close to Ek potential)

52. THE ACTION POTENTIAL

53. ACTION POTENTIAL
Conveys information over distance in the nervous system
Rapid reversal of the membrane potential at rest

54. ACTION POTENTIAL
The Generation of an Action Potential is caused by depolarization of the
membrane beyond threshold
“All-or-none” event
Chain reaction
e.g., Puncture foot, stretch membrane of nerve fibers
Opens Na+-permeable channels Na+ influx depolarized
Membrane reaches threshold action potential

55. ACTION POTENTIAL
A way to study the properties of AP is the Generation of Multiple Action Potentials
Artificially - inject current into a neuron using a microelectrode

56. ACTION POTENTIAL
Firing frequency reflects the magnitude of the depolarizing current
The maximum firing frequency is 1000 Hz. This means that after an AP, is not
possible to initiate another one for at least 1 msec (absolute refractory period).
Also the initiation of another AP after few msec requires more current
(relative refractory period).

57. THE ACTION POTENTIAL IN THEORY
If only K+ channel are open then the membrane would reach EK+

58. THE ACTION POTENTIAL IN THEORY
But if the membrane is also permeable to Na+ , the EP will go towards ENa+
Rising phase (depolarization):
Inward sodium current
Falling phase (repolarization):
Outward potassium current

59. THE ACTION POTENTIAL IN REALITY
First described by Hodgkin and Huxley, with the use of a voltage Clamp: “Clamp”
membrane potential at any chosen value
Rising phase  transient increase in gNa, influx of Na+ ions
Falling phase  increase in gK, efflux of K+ ions
Existence of sodium “gates” in the axonal membrane sensitive to change
in membrane potential and selective for Na

60. THE ACTION POTENTIAL IN REALITY
The Voltage-Gated Sodium Channel
1) sensitivity to change in membrane potential
2) selectivity for Na

61. THE ACTION POTENTIAL IN REALITY
The Voltage-Gated Sodium Channel
Open with little delay
Stay open for about 1msec
Cannot be open again by
depolarization (Absolute
refractory period: Channels
are inactivated)

62. THE ACTION POTENTIAL IN REALITY
The Voltage-Gated Potassium Channels
Open in response to depolarization but later than sodium gates
Potassium conductance serves to rectify or reset membrane potential
(Delayed rectifier)
Structure: Four separate polypeptide subunits join to form a pore

63. THE ACTION POTENTIAL IN REALITY
To summarize- Key Properties of the Action
Potential are
•Threshold
•Rising phase
•Overshoot
•Falling phase
•Undershoot
•Absolute refractory period
•Relative refractory period

64. THE ACTION POTENTIAL CONDUCTION
Down axon to the axon terminal
Orthodromic: Action potential travels in one direction
Antidromic (experimental): Backward propagation
Typical conduction velocity: 10 m/sec and length of action potential: 2 msec

65. THE ACTION POTENTIAL CONDUCTION
Factors Influencing Conduction Velocity:
1) Spread of action potential along membrane follows the path of less
resistance. It depends upon axon structure and direction of positive
charge
2) Path of the positive charge
Inside of the axon (faster)
Across the axonal membrane (slower)
3) Axonal excitability
Axonal diameter (bigger = faster)
Number of voltage-gated channels opens

66. THE ACTION POTENTIAL CONDUCTION
Layers of myelin sheath facilitates current flow (saltatory conduction)
Myelinating cells
1) Schwann cells in the PNS
2) Oligodendroglia in CNS

67. THE ACTION POTENTIAL CONDUCTION
Saltatory conduction
0.2 - 2 mm

68. THE ACTION POTENTIAL INITIATION

69. SYNAPTIC TRANSMISSION

70. SYNAPTIC TRANSMISSION
1897: Charles Sherrington- “synapse”
The process of information transfer at a synapse
Plays role in all the operations of the nervous system
Information flows in one direction: Neuron to target cell
First neuron = Presynaptic neuron
Target cell = Postsynaptic neuron
Types of synapses:
1) Chemical (1921- Otto Loewi)
2) Electrical (1959- Furshpan and
Potter)

71. ELECTRICAL SYNAPSES
Gap junction
Cells are said to be “electrically coupled”
Flow of ions from cytoplasm to cytoplasm
and in both directions
Transmission is fast

72. ELECTRICAL SYNAPSES
An AP in the pre synaptic cell, generate a PSP (post synaptic potential) in the
post synaptic cell
If several PSPs occur simultaneously to excite a neuron this generates an AP
(Synaptic integration)

73. CHEMICAL SYNAPSES
Key elements:
Synaptic cleft (wider the gap junction);
Presynaptic element (usually an axon terminal )
Synaptic vesicles (storage of neurotransmitter)
Secretory granules (bigger vesicles)
Postsynaptic density (receptor that converts chemical signal
into electrical signal )
Postsynaptic cell

74. CNS SYNAPSES
Axodendritic: Axon to dendrite
Axosomatic: Axon to cell body
Axoaxonic: Axon to axon
Dendrodendritic: Dendrite to dendrite
Gray’s Type I: Asymmetrical,
excitatory
Gray’s Type II: Symmetrical,
inhibitory

75. NEUROMUSCULAR JUNCTION
Synaptic junction outside the CNS
Studies of NMJ established
principles of synaptic transmission
One of the largest and faster
synapses in the body

76. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Basic Steps
• Neurotransmitter synthesis
• Load neurotransmitter into synaptic vesicles
• Vesicles fuse to presynaptic terminal
• Neurotransmitter spills into synaptic cleft
• Binds to postsynaptic receptors
• Biochemical/Electrical response elicited in postsynaptic cell
• Removal of neurotransmitter from synaptic cleft

77. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Neurotransmitters
Amino acids: Small organic molecules
stored in and released from synaptic
vesicles (Glutamate, Glycine, GABA)
Amines: Small organic molecules stored
in and released from synaptic vesicles
(Dopamine, Acetylcholine, Histamine)
Peptides: Short amino acid chains (i.e.
proteins) stored in and released from
secretory granules (Dynorphin,
Enkephalins)

78. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Neurotransmitter Synthesis and Storage
A part from amino acids, amines and peptides are synthesized from precursors only in neuron
that release them.
Amine and amino acids are synthesized in the axon terminal and the take up by the vesicles
with the help of the transportes .
Peptides are synthesized in the rough ER, eventually split in the Golgi apparatus and then
carried to the axon terminal in the secretory granules

79. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Neurotransmitter release by exocytosis
AP opens voltage gate calcium channel
Process of exocytosis stimulated by release of intracellular calcium, [Ca2+]I, due to the AP.
Vesicle membrane fuses into presynaptic membrane with subsequent release of neurotransmitter
Vesicle membrane recovered by endocytosis and then refilled with new neurotransmitter

80. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Neurotransmitter Receptors and Effectors (postsynaptic cell)
Ionotropic: Transmitter-gated ion channels Metabotropic: G-protein-coupled receptor
Autoreceptors: Presynaptic receptors sensitive to neurotransmitter released by presynaptic
terminal. Act as safety valve to reduce release when levels are high in synaptic cleft
(autoregulation)

81. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
EPSP: Transient postsynaptic
membrane depolarization by
presynaptic release of
neurotransmitter
IPSP: Transient hyperpolarization
of postsynaptic membrane
potential caused by presynaptic
release of neurotransmitter

82. PRINCIPLES OF CHEMICAL SYNAPTIC
TRANSMISSION
Neurotransmitter Recovery and Degradation
Neurotransmitter must be cleared from the synaptic cleft. Different ways.
Diffusion: Away from the synapse
Reuptake: Neurotransmitter re-enters presynaptic axon terminal
Enzymatic destruction inside terminal cytosol or synaptic cleft
Desensitization: e.g., AChE cleaves Ach to inactive state

83. PRINCIPLES OF SYNAPTIC INTEGRATION
Synaptic Integration
Process by which multiple synaptic potentials combine within one postsynaptic
neuron

84. PRINCIPLES OF SYNAPTIC INTEGRATION
Quantal Analysis of EPSPs
The synaptic vesicle is the elementary units of synaptic transmission
The amplitude of an EPSP is some multiple of the response to the content of a vesicle
(quantum)
Quantal analysis is used to determine number of vesicles that release during
neurotransmission
Miniature postsynaptic potential (“mini”) are normally generated spontaneously

85. PRINCIPLES OF SYNAPTIC INTEGRATION
EPSP Summation
Allows for neurons to perform sophisticated computations. EPSPs are added together to
produce significant postsynaptic depolarization. Two types:
Spatial: EPSP generated simultaneously in different spaces
Temporal: EPSP generated at same synapse in rapid succession

86. PRINCIPLES OF SYNAPTIC INTEGRATION
Inhibition
Action of synapses to take membrane potential away from action potential threshold
IPSPs and Shunting Inhibition
Excitatory vs. inhibitory synapses: Bind
different neurotransmitters (GABA or Glycine),
allow different ions to pass through channels
(Chloride, Cl-)
Membrane potential less negative than -65mV
= hyperpolarizing IPSP
Shunting Inhibition: Inhibiting current flow from
soma to axon hillock

87. PRINCIPLES OF SYNAPTIC INTEGRATION
The Geometry of Excitatory and Inhibitory Synapses
Excitatory synapses (Glutamate) usually have Gray’s type I morphology
Clustered on soma and near axon hillock
Inhibitory synapses (GABA, Glycine) have Gray’s type II morphology
Gray’s Type I: Asymmetrical, excitatory
Gray’s Type II: Symmetrical, inhibitory

88. PRINCIPLES OF SYNAPTIC INTEGRATION
Modulation
Synaptic transmission that modifies effectiveness of EPSPs generated by other
synapses with transmitter-gated ion channels
Example: Activating NE β receptor

89. NEUROTRANSMITTER SYSTEMS

90. NEUROTRANSMITTER
Basic criteria:
1. The molecule must be synthetized and stored in the presynaptic neuron
2. The molecule must be released by the presynaptic axon terminal upon
stimulation
3. The molecule, when experimentally applied, must produce a response in the
postsynaptic cell that mimics the response generated by the release of the
neurotransmitter by the presynaptic cell

91. HOW TO STUDY NEUROTRASMITTERS
Localization of Transmitters and Transmitter-synthesizing enzyme
Immunocytochemistry
Anatomically localize particular molecules to particular cells

92. HOW TO STUDY NEUROTRASMITTERS
Studying Transmitter Localization
In situ hybridization
mRNA strands can be detected by complementary probe
Probe can be radioactively labeled - autoradiography

93. HOW TO STUDY NEUROTRASMITTERS
Studying Transmitter Release
Loewi and Dale identified Ach as a transmitter
CNS contains a diverse mixture of synapses that use different
neurotransmitters
impossible to stimulate a single population of synapses
Brain slice as a model (ex vivo, brain in a dish)
Kept alive in vitro  Stimulate synapses, collect and measure
released chemicals (mixture)
Often stimulated by high K+ solution to cause massive synaptic release
Ca2+ dependency of the release has to be confirmed

94. HOW TO STUDY NEUROTRASMITTERS
Studying Receptors
No two transmitters bind to the same receptor; however one neurotransmitter
can bind to many different receptors
Receptor subtypes
Neuropharmacology
Subtype specific agonists and antagonists
ACh receptors
Skeletal muscle Heart

95. HOW TO STUDY NEUROTRASMITTERS
Studying Receptors

96. HOW TO STUDY NEUROTRASMITTERS
Studying Receptors
Ligand-binding methods
Drugs that interact selectively with neurotransmitter receptors were used
to analyze natural receptors
Solomon Snyder and opiates
Identified receptors in brain
Subsequently found endogenous opiates
Endorphins, dynorphins, enkephalins
Enormously important for mapping the anatomical distribution of different
neurotransmitter receptors in brain

97. NEUROTRASMITTER CHEMISTRY
Cholinergic (ACh) Neurons
good marker for cholinergic neurons
Rate-limiting step of
Ach synthesis
Secreted from the axon
terminal and associated with
axon terminal membrane

98. NEUROTRASMITTER CHEMISTRY
Cholinergic (ACh) Neurons
Synthesis
Degradation

99. NEUROTRASMITTER CHEMISTRY
Catecholaminergic Neurons
Involved in movement, mood, attention,
and visceral function
Tyrosine: Precursor for three amine
neurotransmitters that contain catechol
group
Dopamine (DA)
Norepinephrine (NE, noradrenaline)
Epinephrine (E, adrenaline)

100. NEUROTRASMITTER CHEMISTRY
Marker for catecholaminergic neurons
Rate limiting, regulated by
physiological signals
•Low-rate release - increased
catecholamine conc. - inhibit TH activity
•High-rate release - increased Ca2+ influx
- boost TH activity
Present in the synaptic vesicles
Present in the cytosol
Released from the adrenal gland as well

101. NEUROTRASMITTER CHEMISTRY
• Serotonergic Neurons
– Serotonin (5-HT,5-
hydroxytryptamine) is derived
from tryptophan
– Regulates mood, emotional
behavior, sleep
– Synthesis of serotonin
• Limited by the availability of
blood tryptophan (diet)
– Selective serotonin reuptake
inhibitors (SSRIs):
Antidepressants

102. NEUROTRASMITTER CHEMISTRY
• Amino Acidergic Neurons
– Amino acid neurotransmitters:
Glutamate, glycine, gamma-
aminobutyric acid (GABA)
– Glutamate and glycine
• Present in all cells - Differences
among neurons are quantitative
NOT qualitative
• Vesicular transporters are specific
to these neurons
– Glutamic acid decarboxylase (GAD)
• Key enzyme in GABA synthesis
• Good marker for GABAergic
neurons
• One chemical step difference
between major excitatory
transmitter and major
inhibitory transmitter

103. THE CENTRAL NERVOUS SYSTEM

104. ANATOMICAL REFERENCES
AXIAL
Caudal/ Rostral/
Lateral Medial Posterior Anterior
Dorsal
CORONAL
Ventral
Rostral/
Anterior
SAGITTAL
Caudal/
Medial Posterior
Lateral

105. THE MENINGES
space
membrane
space
Artery
Brain
The meninges are filled with cerebrospinal fluid (CSF)
Insula

106. Whole Brain GM WM CSF

107. THE CNS
Cerebrum
Brainstem
Cerebellum

108. MAJOR SULCI
Longitudinal sulcus

109. MAJOR SULCI
Central sulcus
Lateral (sylvian) fissure

110. CEREBRAL LOBES
Parietal
Frontal
Occipital
Temporal

111. CEREBRAL LOBES
Insula

112. CEREBELLUM
Left Cerebellar Hemisphere Right Cerebellar Hemisphere
Insula
Vermis

113. WHITE MATTER TRACTS
Left Cerebellar Hemisphere Right Cerebellar Hemisphere
Insula
Vermis

114. FUNCTIONAL CLASSIFICATION

115. BROADMANN’S CLASSIFICATION
Insula

116. THE CNS
Thalamus
Telencephalon
Pineal body
Diencephalon
Hypothalamus
Tegment
Tectum Cerebellum
Midbrain
Pons
Medulla
Insula

117. THE VENTRICULAR SYSTEM
Lateral
ventricles
Third ventricle
Fourth ventricle
third Fourth ventricle
ventricle
Fourth ventricle
fourth
ventricle
Lateral ventricles
Fourth ventricle
Insula

118. THALAMIC NUCLEI
Insula

119. CEREBRAL CIRCULATION
Anterior Cerebral Artery
Anterior Communicating
Artery
Middle Cerebral Artery
Internal Carotid Artery
Posterior
Communicating Artery
Posterior Cerebral Artery
Superior Cerebellar
Artery
Basilar
Artery
Insula
Vertebral Arteries

120. CEREBRAL CIRCULATION
Terminal branches of
Anterior Cerebral Artery
Middle Cerebral Artery Terminal branches of
Posterior Cerebral Artery
Insula

121. CEREBRAL CIRCULATION
Anterior Cerebral
Artery
Posterior Cerebral Artery
Insula
Posterior Communicating Artery

122. CEREBRAL CIRCULATION
Anterior Cerebral Artery
Surface branches supply cortex and white matter of :
1)inferior frontal lobe
2)medial surface of the frontal and parietal lobes
3)anterior corpus callosum
Posterior Cerebral Artery
Surface branches supply cortex and white matter of:
1)medial occipital lobes
2)inferior temporal lobes
3)posterior corpus callosum
Middle Cerebral Artery
Surface branches supply cortex and white matter of:
hemispheric convexity (all four lobes and insula).
Insula

123. CEREBRAL CIRCULATION
Middle Cerebral Artery Stroke
Most common stroke syndrome. Symptoms:
-contralateral weakness (face, arm, and hand more than legs)
-contralateral sensory loss (face, arm, and hand more than legs)
-visual field cut (damage to optic radiations)
-aphasia: language disturbances (more likely with L. Hemi. Damage)
-impaired spatial perception (more likely after R. Hemi. Damage)
Insula

124. CEREBRAL CIRCULATION
Anterior Cerebral Artery
- Motor disturbance contralateral distal leg
- urinary incontinence
- speech disturbance (may be more of a motor problem)
- apraxia of left arm (sympathetic apraxia) if anterior
corpus callosum is affected
- if bilateral may cause apathy, motor inertia, and
muteness
Posterior Cerebral Artery
Visual disturbances:
-contralateral homonymous hemianopsia (central vision is often spared)
-L. Hemi: lesions alexia (with or without agraphia)
-Bilateral lesions: cortical blindness : patients unaware they cannot see
-Memory impairment if temporal lobe is affected
Insula

125. CRANIAL NERVES
Insula
Posterior Communicating Artery

126. THE CHEMICAL SENSES

127. THE CHEMICAL SENSES
Animals depend on the chemical senses to identify nourishment
Chemical sensation
Oldest and most common sensory system with the aim to detect
environmental chemicals
Chemical senses
Gustation & Olfaction (separate but processed in parallel)
Chemoreceptors

128. TASTE
The Basics Tastes
Saltiness, sourness, sweetness, bitterness, and umami.
Innate preferences and rejections for particular tastes (sweet and
bitter) have a survival reasons
Usually there is correspondence between chemical ingredients and
taste:
Sweet—sugars like fructose, sucrose, artificial sweeteners
(saccharin and aspartame)
Bitter—ions like K+ and Mg2+, quinine, and caffeine
Salty—salts
Sour—acids
How to distinguish the countless unique flavors of a food
1) Each food activates a different combination of taste receptors
2) Distinctive smell (it combines with taste to give the flavor)
3) Other sensory modalities (texture and temperature)

129. TASTE
The Organs of Taste
Tongue, mouth, palate, pharynx, and epiglottis
Nasal cavity for smell

130. TASTE
Areas of sensitivity on the tongue (but most of the tongue is sensitive to all basics
tastes)
Tip of the tongue: Sweetness
Back of the tongue : Bitterness
Sides of tongues: Saltiness and sourness
Papillae (taste receptors)
Foliate
Vallate
Fungiform
At threshold concentration
(just enough exposure of
single papilla to detect taste)
they respond to only one taste.
More concentrations lead to
less selectivity

131. TASTE
Tastes Receptor Cells
Apical end is the chemically sensitive part. It has small extensions called microvilli
that project into the taste pore.
Receptor potential: Voltage shift – depolarization of the membrane cause CA++
entering the cell and release of transmitter

132. TASTE
Transduction: process by an environmental stimulus cause an electrical response
in a sensory receptor.
In the case of taste, chemical stimuli (tastants) may:
1)Pass directly through ion channels
2)Bind to and block ion channels
3)Bind to G-protein-coupled receptors
Slightly different mechanisms for saltiness, sourness, bitterness, sweetness and
umami (amino acids)

133. TASTE
Saltiness
Special Na+ selective channel.
The ion pass directly through channel
causing deporalization
Sourness
Sourness- acidity – low pH
H + binds to and block ion channels
causing deporalization

134. TASTE
Bitterness
Bitter substances are detected by different types
T1R and T2R receptor. They work as G-protein
coupled receptors
Sweetness
It also detected by receptors T1R2+T1R that
have the same signaling mechanism (cf. bitter
taste)
The expressed in different taste cells allow the
system not to be confused about the taste
Umami
Umami receptors T1R1+T1R3 detect amino
acids

135. TASTE
Bitterness Sweetness Umami

136. TASTE
VII Facial nerve
IX Glossopharyngeal nerve
X Vagus nerve
They carry primary gustatory
axons
Gustatory nucleus
Point where taste axons bundle and
synapse
Ventral posterior medial nucleus
(VPM)
Deals with sensory information from
the head
Primary gustatory cortex (Insula)
Receives axons from VPM taste
neurons
Lesion in VPM and Gustatory cortex
can cause ageusia- the loss of taste
perception

137. SMELL
Smell is not only important for taste but also for social communication
Pheromones are important signals
• Reproductive behavior
• Territorial boundaries
• Identification
• Aggression

138. SMELL
The Organs of Smell
1)Olfactory epithelium: contains olfactory receptor cells, supporting cells (produce mucus),
and basal cells (source of new receptor cells)
2)Olfactory axons constitute olfactory nerve
3)Cribriform plate: A thin sheet of bone through which small clusters of axons penetrate,
coursing to the olfactory bulb
Anosmia: Inability to smell

139. SMELL
Olfactory Transduction
Receptor potential: if strong enough generates APs in the cell body and
spikes will propagate along the axon

140. SMELL
Adaptation: decreased response despite continuous stimulus. Common features of sensory
receptors across modalities
Each receptor cell express a single
olfactory receptor protein.
They responds to different odours
but with preferences.
Many different cells are scattered
into the epithelium

141. SMELL
Central Olfactory Pathways
Mapping of receptor cell into glomeruli is extremely precise

142. SMELL
Axons of the olfactory tract branch and enter the forebrain (unconscious perception)
bypassing the thalamus
Neocortex (conscious perception) is reached by a pathway that synapses in the medial
dorsal nucleus of the thalamus

143. THE EYE

144. LIGHT
Vision is probably the most important sense in humans and animals. This system works by
transducing the property of light into a complex visual percept
Light is an electromagnetic radiation visible to the eye. It’s defined by 3 parameters:
wavelength (distance btw two peaks or troughs)
frequency (number of waves per second)
amplitude (difference btw wave trough and peak)
The energy content of a radiation is
proportional to his frequency.
Only a small part of the
electromagnetic spectrum is visible
to our eyes

145. LIGHT
Optics is the study of light rays and their interactions
Reflection: bouncing of light rays off a surface
Absorption: transfer of light energy to a particle or surface
Refraction: changing of a direction due to change in speed of light rays, due to the passing from one
medium to another

146. ANATOMY OF THE EYE
Pupil: Opening where light enters
the eye
Sclera: White of the eye
Iris: Gives color to eyes. Contains 2
muscles that give size to the pupil
Cornea: Glassy transparent external
surface of the eye
Extraocular muscles: move the
eyeball in the orbit
Optic nerve: Bundle of axons from
the retina

147. THE RETINA
Optic disk: where blood vessels
originate and axons leave the retina
Macula: part of retina for central
vision
Fovea: marks the center of the retina

149. CROSS SECTION OF THE EYE
Ciliary muscles: Ligaments that suspend lens
Lens: Change shape to adjust focus. It divides eyes into two compartments:
1) anterior chamber containing aqueous humor
2) posterior chamber containing vitreous humor
zonule fibers retina
iris
lens
fovea
light
cornea
aqueous humor
optic nerve
ciliary muscles
vitreous humor
sclera

150. IMAGE FORMATION
Eye collects light, focuses on retina, forms images.
The cornea is the site of most of the refractive power of the eye
Focal distance: from refractive
surface to the point where the
rays converges. Depends on
the curvature of the cornea

151. IMAGE FORMATION
Accommodation by the Lens
Changing shape of lens allows for extra focusing power

152. IMAGE FORMATION

153. IMAGE FORMATION
The Pupillary Light Reflex
Depends on connections between retina and brain stem neurons that control
muscle around pupil and aim to continuously adjust to different ambient light
levels. It is consensual for both eyes
The Visual Field
Amount of space viewed by the retina when the
eye is fixated straight ahead
Visual Acuity
Ability to distinguish two nearby points
Visual Angle: Distances across the retina
described in degrees

154. MICROSCOPIC ANATOMY OF THE RETINA
Photoreceptors: cells that convert light energy into neural activity
In the Retina cells are organized in layers . Inside-out

155. MICROSCOPIC ANATOMY OF THE RETINA
Photoreceptor Structure
Transduction of electromagnetic radiation to
neural signals
Four main regions
1) Outer segment
2) Inner segment
3) Cell body
4) Synaptic terminal
Types of photoreceptors
Rods (scotopic vision-dark) and cones
(photopic vision-light)

156. MICROSCOPIC ANATOMY OF THE RETINA
Regional Differences in Retinal Structure
Varies from fovea to retinal periphery
In peripheral retina there is higher ratio of
rods to cones, and higher ratio of
photoreceptors to ganglion cells resulting in
more sensitive to light
In the fovea (pit in retina) visual acuity is
maximal. In Central fovea there are only
cones (no rods) and 1:1 ratio with ganglion
cells

157. PHOTOTRANSDUCTION
Phototransduction in Rods
Depolarization in the dark: “Dark current” and hyperpolarization in the light
One opsin in rods: Rhodopsin
Receptor protein that is activated by light
G-protein receptor Photopigment

158. PHOTOTRANSDUCTION
Depolarization in the dark:
“Dark current” and
hyperpolarization in the light:
Constant inward sodium
current
Light activate an enzime that
destroy the cGMP, causing
the closing of Na+ channel

159. PHOTOTRANSDUCTION

160. PHOTOTRANSDUCTION
Phototransduction in Cons
Similar to rod phototransduction
Different opsins sensitive to different wavelengths: Red, green, blue
Color detection is determined by the relative
contributions of blue, green, and red cones to
retinal signal (Young-Helmholtz trichromacy
theory of color vision)
Dark and Light Adaptation is the transition
from photopic to scotopic vision (20-25
minutes). It’s determined by:
Dilation of pupils
Regeneration of unbleached
rhodopsin
Adjustment of functional circuitry

161. RETINAL PROCESSING
Photoreceptors release glutamate when depolarized
Bipolar Cells. Can be categorized in 2 classes: OFF bipolar cells (they respond to
glutamate by depolarizing) and ON bipolar cells (they respond to glutamate by
hyperpolarizing) . Light off or on causes depolarization

162. RETINAL PROCESSING
Ganglion Cell Receptive Fields
On-Center and Off-Center cells
Responsive to differences in illumination

163. RETINAL PROCESSING
Two types of ganglion cells in monkey and human retina
M-type (Magno) and P-type (Parvo) – 5 and 90 % of the ganglion cell population. The rest 5 % is non-P
and non-M cells
M-type: larger receptive
field, faster conduction of AP,
more sensitive to low contrast stimuli
Color-Opponent Ganglion Cells

164. RETINAL PROCESSING

165. THE CENTRAL VISUAL SYSTEM

166. RETINOFUGAL PROJECTION
It’s the neural pathway that leaves the eye and it include:
The Optic Nerve, Optic Chiasm, and Optic Tract

167. RETINOFUGAL PROJECTION
The visual field is the entire region of the space that could be seen by both
eye looking straight ahead. Right and Left Visual Hemifields are defined
by the space divided by the midline
temporal
retina
nasal
temporal retina
retina

168. RETINOFUGAL PROJECTION
LGN
Optic radiation
R optic tract
retina V1
R LGN
R optic
radiation
V1

169. RETINOFUGAL PROJECTION
Transection
Optic nerve
Transection
Optic chiasm
Transection
Optic tract

170. THE LATERAL GENICULATE NUCLEUS
In the LGN is present the segregation of input by Eye and by Ganglion Cell Type

171. THE STRIATE CORTEX
Retinotopy
Neighboring representation of the object are spatially kept along all the visual
pathway
In the cortex there is an overrepresentation of central visual field
Perception is based on the brain’s interpretation of this information

172. THE STRIATE CORTEX

173. THE STRIATE CORTEX
Lamination of the Striate Cortex (I – VI)
Spiny stellate cells: Spine-covered dendrites mainly in layer IVC, they
receive information from LGN
Pyramidal cells: Spines; thick apical dendrite; mainly layers III, IVB, V, VI
Inhibitory neurons: Lack spines; All cortical layers; Forms local connections
Magnocellular LGN neurons: Project to layer IVCα
Parvocellular LGN neurons: Project to layer IVCβ
Koniocellular LGN axons: Bypasses layer IV to make synapses in layers II and III

174. THE STRIATE CORTEX
Outputs of the Striate Cortex:
Layers II, III, and IVB: Projects to other cortical areas
Layer V: Projects to the superior colliculus and pons
Layer VI: Projects back to the LGN
Receptive Fields in Layer IV C
Layer IVC: Monocular; center-surround
receptive field (like in LGN)
Layer IVCα: Insensitive to the wavelength
– projection from Magno
Layer IVCβ: Center-surround color
opponency - projection from Parvo
Binocularity
Layers superficial to IVC: First binocular
receptive fields in the visual pathway

175. THE STRIATE CORTEX
Ocular Dominance Columns
Information coming from the left and the right eye (already segregate in LGN) is kept
separate in layer IV of the visual cortex
Only on layer III mixing of the
information from the two eyes

176. THE STRIATE CORTEX
Cytochrome Oxidase Blobs
Cytochrome oxidase is a mitochondrial enzyme used for cell metabolism
Blobs: Cytochrome oxidase staining in cross sections of the striate
cortex. Each centered on a ocular dominance stripe in layer IV
Color-sensitive, monocular, with no orientation
or direction selectivity.
They are specialized for the analysis of object
color
The neuron observed in the space between
Blobs (interblob) are binocular, with
orientation or direction selectivity.

177. THE STRIATE CORTEX
Receptive Fields outside Layer IVC
Orientation Selectivity: Neuron fires action
potentials in response to bar of particular
orientation

178. THE STRIATE CORTEX
Receptive Fields
Direction Selectivity: Neuron fires action potentials in response to moving bar
of light

179. THE STRIATE CORTEX
Parallel Pathways: Magnocellular; Koniocellular; Parvocellular

180. THE STRIATE CORTEX
Cortical Module: dimension of 2x2mm.
Necessary and sufficient module for the visual perception

181. THE EXTRASTRIATE CORTEX
Dorsal stream (V1, V2, V3, MT, MST, Other
dorsal areas)
Analysis of visual motion and the visual
control of action
In Area MT (temporal lobe) most cells:
Direction-selective; Respond more to the
motion of objects than their shape
Area MST (parietal lobe) for navigation,
directing eye movements, motion
perception
Ventral stream (V1, V2, V3, V4, IT, Other
ventral areas)
Perception of the visual world and the
recognition of objects,
Area V4 orientation and perception of
color
Area IT is major output of V4. Receptive
fields respond to a wide variety of colors
and abstract shapes. Important also for
memory

182. THE AUDITORY AND VESTIBULAR
SYSTEMS

183. THE NATURE OF SOUND
Sound is an audible variations in air pressure, defined by:
1) frequency: Number of cycles (distance between successive compressed patches)
per second expressed in units called Hertz (Hz). Human Range is btw 20 Hz to 20,000 Hz
2) Intensity: Difference in pressure between compressed and rarefied patches of air. It
determines the loudness of the sound.
Sounds propagate at a constant speed: 343 m/sec

184. THE AUDITORY SYSTEM

185. THE MIDDLE EAR
Sound Force (pressure) is amplified by the Ossicles, producing greater pressure at oval window
(smaller surface) than tympanic membrane, in order to move more efficiently the fluid inside the
cochela
The Attenuation Reflex: response where onset of loud sound causes tensor tympani and
stapedius muscle contraction. It’s used to adapt ear to loud sounds, or understand speech better
in noisy environment (more attenuation of low sounds)

186. THE INNER EAR
Perilymph: Fluid in scala vestibuli and scala tympani
Endolymph: Fluid in scala media
Endolymph has an electric potential 80 mV more positive than perilymph (Endocochlear potential)

187. THE INNER EAR
Basilar Membrane is wider at apex, stiffness decreases from base to apex

188. THE INNER EAR
Pressure at oval window, pushes perilymph into scala vestibuli, round window membrane bulges
out. Endolymph movement bends basilar membrane near base, wave moves towards apex

189. THE INNER EAR
The Organ of Corti and Associated Structures. Here the mechanical energy of the
sound is transformed in electrical signal by the auditory receptor cells (hair cells).
Each hair cells has around 100 stereocilia.
Rods of corti provide structural support. Hair cells form synapses with bipolar neurons
that have their body in the spiral ganglion. Their axons form the auditory nerve

190. THE INNER EAR
Transduction by Hair Cells
When sound arrives, basilar membrane moves. According to the movement, stereocilia
bends on one or the other direction: i.e. Basilar membrane upward, reticular lamina up
and stereocilia bends outward

191. THE AUDITORY PATHWAY
Auditory
cortex A1
MGN
MGN
Superior
olive
Auditory nerve

192. INFORMATION ABOUT THE SOUND
Information About Sound Intensity is encoded in 2 ways:
Firing rates of neurons and number of active neurons
Stimulus Frequency
Frequency sensitivity: in Basilar membrane is Highest at base, lowest at
cochlea apex. This coding is kept separate along the auditory pathways
(tonotopy)
Phase Locking is another way to code for frequency
Consistent firing of cell at same sound wave phase. Only for frequency below
4kHz

193. SOUND LOCALIZATION: HORIZONTAL PLANE
Interaural time delay: Time taken for Interaural intensity difference: Sound at
sound to reach from ear to ear high frequency from one side of ear
Sound Sound
Sound shadow waves
waves Sound
waves
Sound
waves Sound
shadow
Sound
shadow
Duplex theory of sound localization:
Interaural time delay: 20-2000 Hz
Interaural intensity difference: 2000-20000 Hz

194. SOUND LOCALIZATION: VERTICAL PLANE
pinna
Path 2, direct sound
Path 2, reflected sound
Path 2, direct sound
Path 2, reflected sound
Path 3, direct sound
Path 3, reflected sound
Based on reflections from the pinna

195. THE AUDITORY CORTEX: BA 41
Axons leaving MGN project to auditory cortex via
internal capsule in an array called Acoustic
Radiation
Primary auditory cortex
Secondary auditory cortex

196. THE VESTIBULAR SYSTEM
Importance of Vestibular System
Balance, equilibrium, posture, head position, eye movement
The Vestibular Labyrinth

197. THE VESTIBULAR SYSTEM
The Otolith Organs (saccule and utricle). Detect force of gravity (linear acceleration)
and tilts (change of angle) of the head.
Saccule is vertically oriented and utricle horizontally oriented
Crystals of calcium carbonate
Bending of the hairs
toward kinocilium:
depolarization

198. THE VESTIBULAR SYSTEM
The Semicircular Canals. Detect rotation of the head and angular acceleration
Crista: Sheet of cells where hair cells
of semicircular canals clustered
Ampulla: Bulge along canal, contains
crista
Cilia: Project into gelatinous cupula
Kinocili oriented in same direction so
all excited or inhibited together
Filled with endolymph
Three semicircular canals on one
side helps sense all possible head-
rotation angles
Each Canal paired with another on
opposite side of head
Rotation causes excitation on one
side, inhibition on the other
endolymph

199. CENTRAL VESTIBULAR PATHWAY
S1/M1
Face area

200. VESTIBULO-OCULAR REFLEX (VOR)
Motion of the head
Function: Line of sight fixed on Motion of the eyes
visual target
Mechanism: Senses rotations of
head, commands compensatory
movement of eyes in opposite
direction.
Connections from semicircular
canals, to vestibular nucleus, to
cranial nerve nuclei excite
extraocular muscles

201. THE SOMATO-SENSORY SYSTEM

202. SOMATIC SENSATION
Enables body to feel, ache, chill. Responsible for feeling of touch and pain
Different from other systems because receptors are widely distributed
throughout all the body and responds to different kinds of stimuli
Types and layers of skin
Hairy and glabrous (hairless)
Epidermis (outer) and dermis (inner)
Functions of skin
Protective function
Prevents evaporation of body fluids
Provides direct contact with world
Mechanoreceptors
Most somatosensory receptors are
mechanoreceptors.
Pacinian corpuscles
Ruffini's endings
Meissner's corpuscles
Merkel's disks
Krause end bulbs

203. TOUCH RECEPTORS

204. TOUCH RECEPTORS
Two-point discrimination varies across the body surface (Importance of fingertips over
elbow). Difference in density of receptors, size of receptive fields, brain tissue devolved in
processing the information
Big toe
sole
calf
back
lip
forearm
thumb
Index finger

205. PRIMARY AFFERENT AXONS
white matter
Gray matter
Dorsal root
Big toe
Dorsal root ganglion
Dorsal root
ganglion cell
receptor
Dorsal Spinal
root nerve
lip Primary Afferent Axons
Aα, Aβ, Aδ, C
C fibers mediate pain and temperature
A β mediates touch sensations

206. PRIMARY AFFERENT AXONS

207. THE SPINAL CORD
Divided in spinal segments (30)- spinal nerves within 4 divisions
Dermatomes (area of the skin innervate by the R and L dorsal roots of a single
spinal segment) have 1-to-1 correspondence with segments

208. THE SPINAL CORD
Division of spinal gray matter: Dorsal horn; Intermediate zone; Ventral
horn
Myelinated Aβ axons (touch-sensitive) mainly synapses in the dorsal
horn with the second order sensory neurons

209. ASCENDING PATHWAYS
Dorsal Column–Medial Lemniscal Pathway The Trigeminal Touch Pathway
Touch information ascends through dorsal Trigeminal nerves
column, dorsal nuclei, medial lemniscus, Cranial nerves
and ventral posterior nucleus to primary
somatosensory cortex
S1
S1
dorsal column
nuclei
VPN trigeminal
nucleus VPN
dorsal column Medial lemniscus
From
face

210. SOMATOSENSORY CORTEX
Primary is area 3b
Receives dense input from VP nucleus
of the thalamus
Lesions impair somatic sensations
Electrical stimulation evokes sensory
experiences
Area 3a receive information from
vestibular system
Area 1 receive information from 3b and
code for texture
Area 2 receive information from 3b and
code for size and shape
Other areas
Posterior Parietal Cortex (5,7)

211. SOMATOSENSORY CORTEX
Cortical Somatotopy (Homunculus)

212. SOMATOSENSORY CORTEX
Cortical Map Plasticity
Remove digits or overstimulate – examine
somatotopy before and after
Showed reorganization of cortical maps

213. SOMATOSENSORY CORTEX
The Posterior Parietal Cortex
Involved in somatic sensation, visual stimuli, and movement planning
Lesion has been associated to: Agnosia, Astereoagnosia and Neglect
syndrome

214. PAIN
Pain - feeling associated to nociception
Nociception - sensory process, provides signals that trigger pain
Nociceptors: Transduction of Pain
Bradykinin , Mast cell activation: Release of histamine
Types of Nociceptors: Polymodal, Mechanical, Thermal and Chemical
Hyperalgesia: higher
sensitivity to pain in tissue
already damaged
Primary occurs in the
damaged tissues and
secondary hyperalgesia in
the surroundings
Bradykinin, prostaglandins,
and substance P
(secondary hyperalgesia)

215. PAIN
Primary Afferents First pain mediated by fast axons and second pain by slower C fibers
Spinal mechanisms
brain
Dorsal root
Ventral root

216. PAIN ASCENDING PATHWAYS
Main differences between touch and pain pathway
Nerve endings in the skin Spinothalamic Pain Pathway
Diameter of axons
Connections in spinal cord
Touch – Ascends Ipsilaterally
Pain – Ascends Contralaterally
Two pathways:
1) Spinothalamic Pain Pathway
2) The Trigeminal Pain Pathway

217. PAIN ASCENDING PATHWAYS

218. REGULATION OF PAIN
Afferent Regulation: gate theory of pain
Dorsal
horn
To dorsal column
To spinothalamic tract

219. REGULATION OF PAIN
Descending pain control pathway. Use of serotonin
Stimulation of the PAG cause deep analgesia
The endogenuos opiates
Opioids and endomorphins Primary auditory cortex
Secondary auditory cortex

220. TEMPERATURE
Thermoreceptors
“Hot” and “cold” receptors.
Varying sensitivities
The Temperature Pathway
Identical to pain pathway
Cold receptors coupled to Aδ
and C
Hot receptors coupled to C

221. THE MOTOR SYSTEM, part I

222. SOMATIC MOTOR SYSTEM
Muscles and neurons that control muscles
Role: Generation of coordinated movements
Parts of motor control
Spinal cord coordinated muscle
contraction
Brain motor programs in spinal cord

223. SOMATIC MOTOR SYSTEM
Types of Muscles
Smooth: digestive tract, arteries, related structures
Striated: Cardiac (heart) and skeletal (bulk of body muscle mass)
In each muscle there are 100 of muscle fibers innervated by a single axon from the CNS
muscle fibers
Axon from CNS
muscle

224. SOMATIC MOTOR SYSTEM
Somatic Musculature
Axial muscles: Trunk movement
Proximal muscles: Shoulder, elbow, pelvis, knee movement
Distal muscles: Hands, feet, digits (fingers and toes) movement
Antagonist Synergist
Flexors
Extensors

225. THE SPINAL CORD
The Lower Motor Neuron
Lower motor neuron: Innervated by ventral
horn of spinal cord
Upper motor neuron: Supplies input to the
spinal cord
Ventral root
Lower motor Ventral horn
Spinal neuron
nerve Muscle fiber
li

226. THE SPINAL CORD
Alpha Motor Neurons
Two lower motor neurons: Alpha and Gamma
Alpha Motor Neurons directly trigger the contraction
of the muscle
Motor Unit: muscle fibers + 1 alpha motor neuron
Motor neuron pool: all alpha motor neuron that
innervate a single muscle
Graded Control of Muscle Contraction by
Alpha Motor Neurons
Varying firing rate of motor neurons (temporal
summation)
Recruit additional synergistic motor units.
More motor units in a muscle allow for finely
controlled movement by the CNS

227. THE SPINAL CORD
Inputs to Alpha Motor Neurons
1) Information about muscle lenght
2) Voluntary control of movement
3) Excitatory or inhibitory in order to generate a spinal motor program
3 1
2

228. THE MOTOR UNITS
Types of Motor Units
Red muscle fibers: Large number of mitochondria and enzymes, slow to contract, can sustain contraction
White muscle fibers: Few mitochondria, anaerobic metabolism, contract and fatigue rapidly
Fast motor units: Rapidly fatiguing white fibers
Slow motor units: Slowly fatiguing red fibers
Hypertrophy: Exaggerated growth of muscle fibers
Atrophy: Degeneration of muscle fibers
Normal Crossed
innervation innervation
slow fast slow fast
slow fast Fast like Slow like

229. THE MOTOR UNITS
Muscle fiber structure
Mitochondria Myofibrils
Sarcolemma: external membrane
Myofibrils: cylinders that contract after an AP
Sarcoplasmic reticulum: reach of Ca2+
T tubules: network that allow the AP to go
through
T tubules
Sarcoplasmic
reticulum
Opening of
T tubules
Sarcolemma

230. THE MOTOR UNITS
The Molecular Basis of Muscle Contraction
Z lines: Division of myofibril into segments by disks
Sarcomere: Two Z lines and myofibril
Thin filaments: Series of bristles. Contains actin
Thick filaments: Between and among thin filaments. Contains
myosin
Sliding-filament model: Binding of Ca2+ to troponin causes
myosin to bind to actin. Myosin heads pivot, cause filaments
to slide

231. THE MOTOR UNITS
Muscle contraction Excitation: Action potential, ACh release, EPSP,
Alpha motor neurons release ACh action potential in muscle fiber, depolarization
ACh produces large EPSP in muscle fibers (via Contraction: Ca2+, myosin binds actin, myosin
nicotinic ACh receptors) pivots and disengages, cycle continues until
EPSP evokes action potential. Ca2+ and ATP present
Action potential triggers Ca2+ release, leads to Relaxation: EPSP end, resting potential, Ca2+ by
fiber contraction ATP driven pump, myosin binding actin covered
Relaxation, Ca2+ levels lowered by organelle
reuptake

232. SPINAL CONTROL
Muscle spindles: specialized structures inside the skeletal muscle. They inform
about the sensory state of the muscle (proprioception)

233. SPINAL CONTROL
The Myotatic Reflex
Stretch reflex: Muscle pulled tendency to pull back
Feedback loop. Monosynaptic
Discharge rate of sensory axons: Related to muscle length
Example: knee-jerk reflex (stretching the quadriceps and consequent contraction)

234. SPINAL CONTROL
Intrafusal fibers: gamma motor neuron
Extrafusal fibers: alpha motor neuron
Gamma Loop
Provides additional control of alpha motor
neurons and muscle contraction
Circuit: Gamma motor neuron intrafusal
muscle fiber Ia afferent axon alpha

235. SPINAL CONTROL
Proprioception from Golgi Tendon Organ.
In series with the muscle fibers. Information about the tension applied to the muscle
Reverse myotatic reflex function: Regulate muscle tension within optimal range
Golgi
Tendon
Organ

236. SPINAL CONTROL
Spinal Interneurons
Synaptic inputs
1)Primary sensory axons
2)Descending axons from brain
3)Collaterals of lower motor neuron axons
Synaptic outputs: alpha motor neuron
Reciprocal inhibition: Contraction of one muscle set Crossed-extensor reflex: Activation of extensor
accompanied by relaxation of antagonist muscle muscles and inhibition of flexors on opposite side
Example: Myotatic reflex
flex flex
extend extend

237. MOTOR PROGRAM

238. THE MOTOR SYSTEM, part II

239. THE MOTOR SYSTEM
The brain influences activity of the spinal cord in order to generate voluntary
movements
Hierarchy of controls
Highest level: Strategy, the goal of the movement and best way to achieve it.
Associated to neocortex and basal ganglia
Middle level: Tactics, the sequence of muscle contraction to achieve the goal.
Associate to motor cortex and cerebellum
Lowest level: Execution, activation of motor neurons that generate the
movement. Associated to brain stem and spinal cord

240. DESCENDING SPINAL TRACTS
Axons from brain descend along two major pathways
Lateral Pathways: involved in voluntary of distal musculature movement
under cortical control
Ventromedial Pathways: involved in control of posture and locomotion,
under brain stem control

241. THE LATERAL PATHWAYS
Base of midbrai
cerebral n
peducle
Right red
nucleus
Medullary
pyramid
pyramidal
decussation
Corticospinal Rubrospinal
tract tract

242. THE VENTROMEDIAL PATHWAYS
Vestibulospinal tract:
information from vestibular
system. Control neck and
back muscles. Guide head
movements
Vestibular nucleus
Vestibulospinal Tectospinal
tract tract
Spinal
cord
Tectospinal tract: information
from retina and visual
system. Guide control eye
movements.

243. THE VENTROMEDIAL PATHWAYS
Pontine reticulospinal tract:
enhance antigravity reflexs,
helps maintaining a standing
posture Cerebellum
pons Pontine
reticular
formation
Medullary
reticular formation
Reticulospinal
tract
Medullary reticulospinal tract:
opposite function
Spinal cord

244. THE MOTOR CORTEX
Area 4 = “Primary motor cortex” or “M1”
Area 6 = “Higher motor area”
Lateral region Premotor area (PMA), controls distal motor units
Medial region Supplementary motor area (SMA), controls proximal motor units

245. THE MOTOR CORTEX
The Contributions of Posterior Parietal and Prefrontal Cortex
Represent highest levels of motor control. Help in deciding about actions and their outcome, by integrating
many source of information
APs of PMA
Area 5: Inputs from areas 3, 1, and 2 neuron
Area 7: Inputs from higher-order visual cortical areas.
They both project to Area 6
Instruction
Trigger

246. THE BASAL GANGLIA
Basal ganglia
Project to the ventral lateral (VLo)
nucleus
Provides major input to area 6
Cortex
Projects back to basal ganglia
Forms a “loop” in order to select and
initiatiate willed movements

247. THE BASAL GANGLIA
Anatomy of the Basal Ganglia
Caudate nucleus, putamen, globus pallidus, subthalamic nucleus
Substantia nigra: Connected to basal ganglia

248. THE BASAL GANGLIA
The Motor Loop: Selection and initiation of willed movements
Excitatory connection from the cortex to cells in putamen
Cortical activation excites putamen neurons. Inhibits globus pallidus neurons.
Release cells in VLo from inhibition. Activity in VLo influences activity in SMA

249. THE BASAL GANGLIA
Basal Ganglia Disorders: Hypokinesia and hyperkinesia
Parkinson’s disease
Symptoms: Bradykinesia, akinesia, rigidity and tremors of hand and jaw
Organic basis: Degeneration of substantia nigra inputs to striatum
Dopa treatment: Facilitates production of dopamine to increase SMA activity
Huntington’s disease
Symptoms: Hyperkinesia, dyskinesia, dementia, impaired cognitive disability,
personality disorder
Hemiballismus
Violent, flinging movement on one side of the body
Some examples….
http://www.youtube.com/watch?v=ECkPVTZlfP8&feature=related PARKINSON

250. THE CEREBELLUM
Function: Sequence of muscle contractions
Lesion: Ataxia, characterized by uncoordinated and inaccurate movements.
Dysynergia, dysmetric
Anatomy: Folia and lobules, Deep cerebellar nuclei (relay cerebellar cortical output
to brain stem structures) Vermis (contributes to ventromedial pathways) Cerebellar
hemispheres (contributes to lateral pathways)

251. THE CEREBELLUM

252. THE CEREBELLUM
The Motor Loop Through the Lateral Cerebellum
Axons from layer V pyramidal cells in the sensorimotor cortex form massive projections to pons
Corticopontocerebellar projection are 20 times larger than pyramidal tract
Function: Execution of planned, voluntary, multijoint movements