Biology Neuroscience Questions

Have you ever
wondered…
1
…about your own identity?
How much of who you are is your biology?
How much of who you are is your environment?
What part of life is “under our control”?
2
…about brain injuries?
How and why does brain injury affect our behavior?
What can we do about it?
3
…how drugs work?
Why do they stop working (tolerance)?
Why do they have the side effects that they do?
When are particular drugs useful?
4
…how we learn?
Why does behavior change with experience?
What happens in the nervous system?
5
…about tools and techniques?
How do we study the brain?
What are the strengths/weaknesses of our approach?
What improvements can be made?
6
…if a computer read your mind?
• Answer: kinda, yeah!* (above chance)
How accurate is the computer?
How do we train a computer to do this?
Why would I ever want anyone to read my mind?
7
…about consciousness?
Are there varying states of consciousness?
If states exist, how are they created?
What functional purpose would different states serve? 8
If you’re interested in any
of these questions, the
discipline of neuroscience
could be a great place for
you.
10
Lecture 1: Introduction to
Neuroscience
Introduction to Neuroscience (HMB200H1S)
Paul Whissell, Ph.D.
11
What is Neuroscience?
• The study of the structure and function of the
nervous system, with a particular focus on the brain
• The subject is a convergence of the scientific
disciplines of psychology, physiology and anatomy
• Gives us insights into the causes of our behavior and
behavioral disorders
• Important to health care as well as day-to-day living
12
The Nervous System
• Divided into central (CNS) and peripheral (PNS)
CNS = brain + spinal cord, encased
in bone (skull and vertebrae,
respectively)
PNS = everything else
outside the CNS
CNS
We almost exclusively focus on the CNS
PNS
13
Purpose of the Nervous System?
• Subject of much debate
• One perspective is that the nervous system exists to
generate movement in a perceptual world created by
the brain
The Real
Reason We
Have Brains
• Cells of the nervous system might be ideally suited for
this purpose because they demonstrate remarkable
adaptations following experience (neuroplasticity)
14
Why did you choose neuroscience?
• To participate in the poll, visit the following URL:
http://etc.ch/dJUx
• Alternatively, scan the following QR code:
• Poll Results
15
Learning Objectives
• Understand the structure/physiology of the nervous
system, with a focus on the brain
• Understand how the nervous system generates
behavior
• Understand how aberrant functions of the nervous
system give rise to behavioral disorders
• Understand the investigative methods used by
neuroscientists and treatments used by health care
professionals
16
Overview
• Part 1: History of Neuroscience
• Part 2: Introduction to the Nervous System
• Part 3: Key Course Information
17
Part 1: History of
Neuroscience
From mentalism to dualism to materialism
18
What causes behavior?
As long as humans have been around, they have
debated about the cause of their thoughts and actions.
Why do we do what we do?
19
History of Neuroscience
• Though recognition of neuroscience as a discipline
occurred in the late 1800s, people have been studying
the brain and speculating about it for millenia
• Many early theories about the brain were brave and
creative, but misguided
• The ancient Egyptians, for example, were aware of the
brain but did not believe it was centrally involved in
behavior (this role was attributed to the heart)
20
Aristotle and Mentalism
• Aristotle (“father of science”)
argued that the psyche was
responsible for behavior
(mentalism)
• Aristotle believed that the psyche
resided in the heart
• Aristotle also argued that the
brain’s purpose was to cool the
blood (reverse is true)
21
Hippocrates and the Brain
• Hippocrates (“the father of medicine”) argued for a
major role of the brain in behavior (~400 BCE)
“Not only our pleasure(s)…but our sorrow(s)…rise in the
brain, and the brain alone. With it we think and
understand, see and hear…discriminate between the
ugly and the beautiful…good and evil.”
• Also argued for a role of humors (internal fluids) in
behavior
Other quotes here (he has a lot)
22
Galen and the Brain
• Greek physician living in the Roman Empire (129 AD –
210 AD) whom argued that the brain was an ideal site
for the generation of behavior
• Worked with injured animals and humans
• Also argued for the importance of humors in behavior
(humorist theory still alive and well)
23
Fluid-based models of behavior
• During the renaissance (1500-1600s), fluid-based
models of behavior emerged that focused on the fluidfilled ventricles within the brain
Ventricles
24
The Mind and the Machine
• A particularly well-known fluid model of behavior was
put forward by Descartes (1662)
• Descartes’ model was partly inspired by his
surroundings, which included machines
25
Descartes and Dualism
• In this model, the body was considered similar to a
complex machine
• Unlike machines, however, humans also had a mind
(or soul) separate from the body
• This view that the body and mind are separate was
termed dualism (persists in some forms today)
• Descartes argued that the pineal gland was the site of
interaction between the mind and body
26
Descartes and Dualism
• Descartes’ model emphasized the importance of fluid
movements through the eye, nerves and pineal gland
in controlling the action of muscles
27
Moving forward…
• Many physicians noticed the correlation between brain
injury and behavior over the years, but rarely was
detailed anatomical data collected
• This limited progress
• Willis (mid 17th century) was one of the first
researchers to study the anatomy of the brain in detail
• Willis and his colleague Wren produced a number of
high-quality drawings of the brain that remained
influential centuries later
28
Localization of brain function
• Gall (18th century) argued that different brain regions
had different functions
• This idea (localized brain function) is true to an extent
A, B + C are different parts of the brain
A, B + C have different functions
• Gall, w/others such as Spurzheim, also suggested that
brain areas developed with use
• This idea (experience-dependent neuroplasticity) is now
widely accepted
• However, the form first proposed will surprise you
29
Phrenology
• Brain areas were related to mental traits and would
change in size with use of those traits
• Changes in the brain would cause changes in the
cranium (e.g. brain area expands, deforms cranium)
• By measuring the cranium, you would understand the
brain underneath + the mental traits it governs
30
Phrenology
• To everyone today and many people of the time,
phrenology was considered a pseudoscience
• However, it included a few concepts which would later
be shown to be well-supported by data
• Much data suggests the brain changes w/experience,
but changes are subtle + never visible externally
• In fact, meaningful changes in the brain (i.e. those
changes which affect behavior) are so subtle they are
tough to detect
31
Onward To Materialism
• With advances in science and technology, it soon
became possible to test many theories for the first time
• Few theories survived this process, but much was
learned in testing them
• Increasingly, researchers focused on objective,
measurable descriptions of behavior that could be
referenced to the brain (via the experimental method)
• This approach (materialism) emerged in the late 1800s
and coincided with a number of big advancements
32
Advances in the 1800s + beyond
• Work of Darwin and Wallace (Evolutionary Theory)
• Emergence of Psychology as a rigorous, scientific
discipline
• Increasing use of electrophysiological techniques to
study the brain
• Apply controlled electrical stimulation to the brain, observe
the response
• Cumulative “mountain” of correlational evidence linking
brain changes to behavioral changes
33
Advances in the 1800s + beyond
• Fluorens
• Studied the effects of lesions to the nervous system on
behavior in birds
• Fristch and Hitzig
• Studied the effects of brain stimulation on movement in dogs
• Dax, Wernicke and Broca
• Observed that left hemisphere damage is commonly
associated with language impairment (aphasia)
• Argued that aphasia was caused by damage to specific brain
regions (e.g. Wernicke’s Area, Broca’s Area)
34
The development of
biological techniques,
particularly staining to
reveal cells, was a critical
event.
Nissl stain revealing neuronal
structure + organization
35
The 1900s – Formal birth of a field
• Ramon Y Cajal (“father of modern neuroscience”’)
advanced staining procedures used by Golgi to
visualize the nervous system
• Argued that the nervous system was made of discrete
individual cells (neuron doctrine) rather than being a
single continuous network (as in reticular theory)
36
The 1900s – Formal birth of a field
• It was later discovered that the many individual cells of
the nervous system were connected to each other
• Sherrington argued that the synapse was the
functional connection between neurons
37
The Brodmann Map (1909)
• Using staining methods, Brodmann studied the
histological structure/organization of neurons
(cytoarchitecture) throughout the brain
• If indeed differences in cell properties had functional
consequences, this would mean that a map of cell
properties could also be map of brain functions
• Brodmann’s work lead to the idea that were at least 52
distinct brains areas (Brodmann Areas/BAs)
38
The Brodmann Map
• Though imperfect, this map was very influential
• Neuroimaging techniques today (common in Cognitive
Neuroscience) often refer to BAs
39
However…
• Newer maps (Talairach/MNI coordinate systems) are
increasingly favored
• These maps are now used in stereotaxic surgery and
experimental approaches
40
However…
• The BA map seems consistent w/the localization of
function idea (one brain area, one function)
• Gradually, we’ve moved from an extreme localization of
function position to a more moderate view
• Today, we understand that a 1) single brain area can
serve multiple functions and 2) any one behavior is the
result of multiple brain areas working together
• We also appreciate that reorganization of the brain can
occur w/experience + injury
41
From the 1950s to Today
• The 1950s represented an explosive growth in the field
of neuroscience, with many amazing discoveries
42
Why is history important?
• Makes us aware of the investment required in any
major advancement
• Time, energy and money
• Highlights what we need to do to succeed1,2
• Work together (collaborate), sharing data and resources
• Read broadly, build evidence-based theories
• Guide replication efforts, eliminate redundancy
• Keeps us forward-thinking and humble
• Most predictions are wrong
• Testing predictions is essential
• We continually have to generate new ideas
Brown. 2019. FBN.
Article by Ed Yong.
43
Part 2: The Nervous
System
44
The Nervous System
45
The Nervous System
• Divided into central (CNS) and peripheral (PNS)
CNS = brain + spinal cord, encased
in bone (skull and vertebrae,
respectively)
PNS = everything else
outside the CNS
CNS
We almost exclusively focus on the CNS
PNS
46
Structure of Your Brain
Neuron
Astroglia
Microglia
Oligodendroglia
~80-90 billion cells in the brain
Two main cell types: neurons and glia (including
astroglia, microglia and oligodendroglia).
47
Neurons are our focus
INPUT
SIGNAL
(receives
transmitter)
Axon
terminals
Dendrites
Axon
Myelin
Cell body
OUTPUT
SIGNAL
(release of
transmitter)
ELECTROCHEMCAL SIGNAL
(Action Potential)
Excitable cells that generate and conduct
electrochemical signals. Next week, we’ll be discussing
48
how these cells work.
Divisions of the Nervous System
49
The meninges covers the brain
• Membrane covering the brain
• Three layers (descending order: dura, arachnoid + pia)
• The meninges cushions the brain against the skull
Infections of the meninges (meningitis) are
extremely serious!
50
Organization of the brain (+ CNS)
51
Organization of the brain (+ CNS)
Cell bodies
Nuclei
Gray matter
Axons
Tracts
White matter
White
matter
Gray
matter
52
The Brain
53
1 – Telencephalon
• The forebrain includes
the cortex (outer
layer) of the brain
• Also included are the
basal ganglia and
limbic system
structures (e.g.
hippocampus,
amygdala and parts of
the olfactory system)
54
The Cortex of the Brain
• Outer layer of cells (cortex means ‘bark’)
• Gray matter (mostly cell bodies of neurons)
• Thin (~2-4 mm in humans)
55
Breaking down the cortex
• Subdivided into two parts:
neocortex (6 layers) +
allocortex (3 layers)*
• In humans, 90% of cortex
is neocortex
• Neocortex is thought to be
phylogenetically newer and
explain the majority of our
higher order behaviors
56
The four lobes of the brain
Frontal
lobe
Parietal
lobe
Temporal
lobe
Bumps = Gyri (s. Gyrus)
Folds = Sulci (s. Sulcus) or Fissures
Occipital
lobe
57
Cortex = outer layer
Frontal cortex = outer
layer of the frontal lobe
58
Surface of the brain
• Longitudinal fissure = divides
the hemispheres
• Central fissure = frontal and
parietal lobes
• Pre-central gyrus before the
fissure (frontal)
• Post-central gyrus after the fissure
(parietal)
• Lateral fissure = top half
(frontal + parietal) from bottom
half (temporal)
59
Limbic System
• Cingulate cortex
• Hippocampus
• Amygdala
• Mamillary body
• Septum
Many functions (though everyone only highlights memory + emotion)
60
Basal ganglia
• Caudate + Putamen
(together = dorsal
striatum) as well as
Globus Pallidus
• Important for Movement
• Nucleus Accumbens and
other structures (= ventral
striatum)
• Role in reinforcement
learning + habit formation
(relevant to addiction)
61
2 – Diencephalon
• Thalamus: relay center for incoming sensory
information (everything except olfactory input)
• Hypothalamus: key drive center (the four fs: fighting,
fleeing, feeding and sweet love)
62
3 – Mesencephalon
• Superior colliculus
(vision-related)
• Inferior colliculus
(auditory-related)
• Substantia nigra
(motor coordination)
• Reticular formation
(arousal)
• Periaqueductal
grey
(nociception/pain)
… and more
63
4 + 5: Met- and Myelencephalon
• Metencephalon
includes pons +
cerebellum
• Myelencephalon is just
the medulla
• Similar organization in
the pons + medulla
Pons
• Important incoming tracts
(sensory information) + Medulla
outgoing tracts (motor
instructions and more)
Cerebellum
64
Key principles of Brain Function
• Localization of function (to an extent)
• Certain brain areas are specialized for certain tasks
• Collaboration is significant
• A network of brain areas works together in any one behavior
• Balance is critical, imbalance often causes dysfunction
• Too much activity, or too little, can be a problem
• Reorganization is possible, with limitations
• The brain changes in response to injury, experience and
learning (neuroplasticity)
65
Neuroplasticity
• A change in the structure or function of neurons is
termed neuroplasticity
• Neuro = pertaining to neurons, plasticity = the quality of
being easily shaped or molded
• Ubiquitous and vital; every experience-dependent
change in behavior involves neuroplasticity
• While some changes in structure and function are
possible, others are not
• Regeneration following injury is very limited in the CNS
• Recovery of function following injury is also often limited
66
Neuroplasticity Events
Learning
Meditation
Postnatal
neurogenesis
Addiction
Stroke rehabilitation
Trauma responses
67
Divisions of the Nervous System
68
The Spinal Cord
Tracts for sending motor instructions out
Tracts for delivering sensory information in
69
From the SC to the PNS
PNS
Nerves
Afferent sensory
information
CNS
Spinal
cord
PNS
Nerves
Efferent motor
information
70
Divisions of the Nervous System
71
The Somatic Nervous System
Cranial nerves (12)
Spinal (peripheral) nerves (31)
72
The ANS
73
ANS activation
• Involuntary effects on organs
• The ANS has Parasympathetic + Sympathetic
Divisions (PaNS/SyNS)
• Many organs receive input from each system
• Effects of PaNS and SyNS differ
• ANS activation is part of the reason emotional states
are accompanied by such strong physiological
changes (sweating, heart-pounding…)
74
PNS versus SNS effects
PNS Dominance
• ↓ respiration
• ↓ heart rate
• ↑ heart rate
variability
• ↓ blood pressure
• ↑ galvanic skin
resistance
• ↓ catecholamines
SNS Dominance
• ↑ respiration
• ↑ heart rate
• ↓ heart rate
variability
• ↑ blood pressure
• ↓ galvanic skin
resistance
• ↑ catecholamines
All these properties can change in emotion!
75
Divisions of the ANS
Autonomic Nervous System
(ANS)
Sympathetic Nervous System
(SNS)
‘Fight or flight’
Parasympathetic Nervous System
(PNS)
‘Rest and digest’
Running from a bear!
‘Food coma’
76
Parasympathetic v. Sympathetic
• Both systems provide input to similar structures
• Contrasting effects on those structures’ functions
• Theory: Imbalance/dominance (e.g. parasympathetic
> sympathetic) is what matters
77
Navigating the Nervous System
Three dimensional
axis system, with:
• Medial-Lateral axis
• Rostral-Caudal axis
• Dorsal-Ventral axis
78
Navigating the Nervous System
• Rostrolateral frontal cortex
• Front, outer part of the frontal cortex
• Dorsolateral frontal cortex
• Top, outer part of the frontal cortex
• Ventromedial hypothalamus
• Bottom, middle part of the hypothalamus
• Posteromedial hypothalamus
• You get the idea
79
Visualizing the Brain along the axes
Coronal
Horizontal
Sagittal
80
Part 3: Key Course
Information
81
Your teaching assistants
• Julia Gallucci ([email protected])
• Tia Kant ([email protected])
• Kasia Pieczonka ([email protected])
• Bianca Rusu ([email protected])
Teaching assistant will mark assessments, run tutorials
and provide other invaluable support throughout the
term.
82
No required textbook
• All testable content comes from the lectures and
tutorials
• For students interested in learning more, the optional
textbook Principles of Neural Science is available (now
in its 6th edition)
83
Two main components to
this course:
1) Lectures
2) Tutorials
84
Component 1 – Lectures
• PDFs
• Recordings (from last term)
• All materials will be made available on/before the
posting date
• Pace yourself; try to read a lecture every two or three
days. There’s a lot of content to learn and it cannot be
done quickly!
85
Component 2 – Tutorials
• Some new content but primary emphasis is on
problem-solving through interactive exercises
• Entirely online via Zoom
• Tutorials are held most Tuesdays and Thursdays* (see
schedule)
• You only have 1 hour of tutorial per week (i.e. the
one you booked when you registered for the course)
86
Marks Distribution
• 30% Term Test 1 (L1-4 + linked tutorials) on July 19
• Online, on Quercus, 2 hours, open book, Format TBA
• 30% Term Test 2 (L5-8 + linked tutorials) on Aug 4
• As above
• 35% Final Assessment (Cumulative)
• In-person, on-campus, 3 hours, closed book, Format TBA
• 5% Three Quizzes: July 14, August 2, August 11
• Online, no time limit (just due date), multiple choice
87
On grading…
• The University of Toronto is a world-class institution
known for a high academic standard
• We will provide a fair evaluation that is consistent with
past years and instructors
• Averages tend to be 70 – 76% every year
• Averages will be shared with students
• The grading process for term tests will be transparent;
you can discuss grades after their release
88
Course Study Guide
• Updated throughout the term
• Major highlights of lectures
• Emphasizes concepts likely to come up on
assessments
• Students who complete the guide tend to perform
better (70%+) on assessments
89
On Academic Integrity…
• U of T is dedicated to academic integrity and fairness
• All work submitted *must* be your own thoughts in your
own words
• Do not ‘collaborate’ with anyone (though you can and
should ask me/your teaching assistant for help)
• If you think something might not be permissible, ask!
90
Our Dialogue in HMB200
• Material is based on our textbook and consensus from
evidence-based research articles in academic journals
• If I missed something, got something wrong or didn’t go
into enough detail for you – let me know!
• Give me the reference and I am happy to read it
• The course is updated every year
91
Frequently Asked
Questions
92
Do I need to buy a textbook?
No. The textbook is optional and only
those exceptionally interested in the
discipline should explore it.
93
Is attending lectures and tutorials
mandatory?
No and no. Having said that,
attendance is strongly
recommended and is correlated
with success.
94
What are the policies for missed
tests and assessments?
HMB has specific policies which
may differ from your academic unit
(see syllabus).
95
Can I check my answers for the
course study guide?
Yes! Office hours is the absolute
best time to do this.
96
Coming soon…
• Our first tutorial will discuss the role of genes in
behavior
• Our next lecture will discuss neurons and
neurotransmission in detail
• Take care, stay safe and hope to see you next class!
97
Lecture 2:
Neurotransmission
Introduction to Neuroscience (HMB200H1)
Paul Whissell, Ph.D.
1
Overview
• Part 1: Cells of the Nervous System
• Focus on Neurons
• Part 2: The Resting Membrane Potential
• Basis of the RMP, Nernst Equation, GHK equation
• Part 3: The Action Potential
• Neurotransmission, Threshold, Refractory Period
• Part 4: Understanding Signaling
• EPSPs vs. IPSPs, Temporal summation, Spatial summation
2
Part 1: Cells of the
Nervous System
3
Cells of the CNS
Neurons
Astroglia
Microglia
Oligodendroglia*
4
1 – Neurons
5
A stylized neuron
INPUT
SIGNAL
(receives
transmitter)
Axon
terminals
Dendrites
Axon
Myelin
Cell body
OUTPUT
SIGNAL
(release of
transmitter)
ELECTROCHEMCAL SIGNAL
(Action Potential)
Excitable cells (generate and conduct electrochemical
signals)
6
Neurotransmission
A
B
Synapse: A site where there is a transmission of
electrochemical impulses between two neurons (A + B) 7
Number of synapses
Each neuron may form 1000 -10 000 synapses
(estimate of total synapses in brain is ~1 000 trillion).
8
Synaptic diversity
• Many types; the classic and most common form is the
axon-dendrite synapse (axodendritic; 3)
9
Synaptic diversity
• Perisomatic (at the soma) and axo-axonic (at the
axon hillock) are also possible
• Autosynapses (self-synapses) also exist
10
2 – Microglia
• Small cells involved in many functions (esp. immune)
• Respond to injury + disease states by multiplying,
engulfing debris or cells (cleaning function)
• Regulate cell death, synapse formation/elimination
Perry. 2013. Sem Immunopath.
11
3 – Astroglia
• Affinity for blood vessels (contract/relax)
• Regulate flow of materials into the CNS; provide
nutritional support for neurons
• Also vital to injury response (like microglia)
• Have receptors, express transporters and release
transmitters
12
Tripatrite synapse
Smith. 2010. Nature.
13
4 – Oligodendroglia
• In the CNS, oligodendroglia myelinate neurons
• In the PNS, Schwann cells perform this function
14
Part 2: The Resting
Membrane Potential
(RMP)
15
The neuronal membrane
• Thin phospholipid bilayer separating inside
(intracellular) from outside (extracellular)
• Most substances cannot easily enter OR leave
(selective permeability)
16
Ions across the membrane
17
Basis of the RMP
• By restricting flow of these
substances, the membrane
creates a charge separation
• Put differently, there is a
potential difference across
the membrane (Vm)
• RMP typically ~ -60 to -70 mV
• RMP is negative due to
buildup of negative charge on
the inside
18
Channels in the membrane
19
Channels are like ‘doors’ in the
membrane.
Some are locked + require a ‘key’ to
open (i.e. will only open under
specific conditions).
When channels open, ion flow
across the membrane – and many
other effects – can occur.
20
How do channels open?
• Opening triggered by different events
• When a channel opens, do ions go inward
(intracellular)? Or do they go outward (extracellular)?
21
The direction of ion flow
across the membrane
(inside or outside) is
determined by two main
factors.
22
Gradients
Concentration differences
across the membrane
Charge across the
membrane
Chemical forces act to
eliminate concentration
gradient
Electrical forces act to
eliminate voltage gradient
23
Net movement of K+ ions
–
–
–
– – – -K+
K+
–
K+
—
K+
–
–
K+
K+
– —-
–
–
CHEMICAL
ELECTRICAL
NET
K+
• Chemical: K+ from high to low conc. (outward; strong)
• Electrical: K+ from positive to negative (inward)
• Net electrochemical driving force is outward
24
Net movement of Na+ ions
–
–
–
– – —
–
Na+
–
Na+
–
—
– —-
–
–
CHEMICAL
Na+
ELECTRICAL
Na+
NET
Na+
• Chemical: Na+ from high to low conc. (inward)
• Electrical: Na+ from positive to negative (inward)
• Net electrochemical driving force is inward (strong)
25
At the RMP
Na+/K+
Exchanger
Leak K+
channels
3Na+
L-gated
channels
CLOSED
V-gated Na+
channels
CLOSED
V-gated K+
channels
CLOSED
K+ K+
K+
++
++
– –
– –
2K+
26
Na+/K+ exchanger
• Exchanges 3 Na+ ions for 2K+ ions at cost of 1ATP
(energy-dependent)
27
At the RMP (Review)
• Leak K+ channels are open
• Na+/K+ pump is active
• Ligand-gated Na+ channels are CLOSED
• Voltage-gated K+ channels are CLOSED
• Voltage-gated Na+ channels are CLOSED
• Because Na+ channels are closed at rest, Na+ ions
cannot enter easily (despite driving force)
28
Equilibrium Potential
• At the RMP, what would happen if we opened all
channels for K+ and Na+?
• Flow of K+ and Na+ ions across the membrane would
occur in the direction of the net electrochemical force
• At the RMP, K+ is outward and Na+ is inward
• Though net flow would be strong initially, it would
progressively decrease and eventually stop (hitting 0)
• Why?
29
Equilibrium Potential
• The flow of an ion changes the electrical and/or
chemical driving force, eventually eliminating it
• As Na+ flows across the membrane, the membrane
becomes depolarized (e.g. Vm = -58 mV, -55 mV…)
• Depolarization of the membrane means less electrical
force and less net driving force for Na+
• Eventually, at a certain Vm, the net driving force will be
0 (equilibrium potential) (or reversal potential)
30
Crude analogy
If you’re dehydrated, you become
thirsty.
If you’re thirsty, there is a strong
drive to drink (driving force).
If you drink water, you’re no longer
dehydrated or thirsty (driving force
is gone).
31
Equilibrium Potential
Approximated using using the Nernst equation:
• R = Gas Constant (8.3 JK-1mol-1)
• T = Temperature (~298 K)
• z = Ionic valence (e.g. +1 for K+, -1 for Cl-)
• F = Faraday’s Constant (96 500 C mol-1)
• [x]o = ionic concentration outside
• [x]i = ionic concentration inside
32
The Nernst Equation
Estimates ionic flow at a given membrane potential
• For Na+ ions at Vm = -60 mV:
• ENa+ = +55 mV, Vm Secondary)
• Segregated representation
• Topographic; e.g. High and low frequency on different cells
• Lateralization; e.g. L visual fields on R visual cortex
• Disproportionate representation
• Representation is linked to adaptive utility, not size (e.g.
more representation for hands than for legs)
• Reorganization is possible (neuroplasticity)
• Injury and learning (sometimes good, sometimes bad)
13
We are not sensitive to every
signal.
There are some signals we
cannot process.
There are many signals of
which we are not consciously
aware.
14
Sensory thresholds
• For each sensory modality, there is a minimum
intensity of a stimulus that we can detect (at above
chance levels, >50%)
• This value is termed the sensory threshold; it varies
between species
• Dogs hear sounds that humans cannot (dog whistles)
• Sensory thresholds vary within the species, especially
in different age groups
• Hearing loss with aging can be explained through changes in
the auditory system
15
Conscious awareness is
not required for a stimulus
to influence behavior.
16
Response without Awareness
• Subjects with blindsight are not aware of visual
stimuli, but still react to them
• Here, a person with blindsight responds to an
emotional face but reports seeing nothing
Response
Sensory
information
Awareness
17
Part 2A: Smell (Olfaction)
18
Olfaction
• Important for survival
• Threat warning (e.g. detect fire + spoiled food)
• Social behavior (recognition of friends, attraction to mates)
• Notably different than other pathways in terms of
processing (especially with regards to the role of
thalamus)
• Compared to other senses, poorly studied and poorly
understood
• This may be because its strength and importance is
undervalued in humans
19
Olfactory Pathway
Pathway: Bipolar Receptor > Glomerulus > Olfactory
nerve > Primary Olfactory Cortex (Pyriform) >
Secondary Olfactory Cortex (OFC)
20
Olfactory receptors
• Detect volatile odorants
• Receptors allow us to recognize many odors
(estimates ~1 trillion)
• It is unclear how odorants interact with receptors
• Many have argued that it is the chemical structure of
odorants which is important (shape theory) but some
have argued for vibrational energy instead (vibrational
theory; controversial)1,2
1. Turin et al. 2015. PNAS.
2. Block et al. 2015. PNAS.
21
Shape Theory
• Odorants activate receptors that are responsive to
their shape (related to their chemical structure)
• An odor compound may contain many chemicals, and
thus may activate a compliment of receptors
22
What is olfaction for,
anyway? What does it do?
23
The ‘Nose Knows’
• Emotional tears do not have a discernable odor, but
influence behavior
• Men smelling women’s emotional tears show less
sexual attraction to women, less arousal during
arousing films
24
Smell + reproduction in humans
• Humans can predict sex accurately from odor
• In women, olfactory sensitivity increases during
ovulation and pregnancy
• Men can judge stage of reproductive cycle from odor
• Odors not regarded as particularly attractive
• Importance for reproduction poorly understood
25
Are humans very poor sniffers?
Our sense of smell was once widely thought to be
inferior to animals because we have:
• a smaller olfactory bulb relative to brain volume than
most animals
• fewer olfactory genes coding for proteins
• no readily identifiable pheromones
26
However, humans…
• have similar amounts of olfactory neurons (~24 million)
to other mammals
• have non-coding olfactory genes can still be
meaningful
• use their sense of smell differently than animals (we
sniff things from far away; it is socially inappropriate for
us to use smell to its fullest extent)
• can learn some olfactory-guided behaviors w/training
(e.g. scent tracking)
27
Loss of smell is a concern
• Anosmia is a risk factor for pathology (TBI,
Alzheimer’s Disease and Parkinson’s Disease)1-3
1. Schofield et al. 2014. Front Neuro.
2. Meshalam et al. 1998. JAMA.
3. Doty et al. 2017. Lancet Neurol.
28
Part 2B: Taste (Gustation)
29
The 5 Tastes
30
The Sense of Taste
In the papillae of your tongue are taste buds. These
buds contain taste (gustatory) cells, which in turn
contain taste receptors. It is taste receptors that
respond to taste molecules.
31
Within the taste bud…
Gustatory cell
Basal cell
Basal cells can be viewed as a type of stem cell which
replace gustatory cells (which you lose constantly).
32
Labeled Line Theory
• Each taste cell expresses only a few receptors (e.g.
pink cells only express sweet + sour) and is
connected with one sensory neuron.
• Based on this model, we might argue that specific
taste cells are responsible for specific tastes.
33
Taste Receptors
• Umami, Sweet + Bitter tastes are mediated by the
activity of G-protein coupled receptors
• Sour + Salty tastes are linked to ion channels (for H+
and Na+ ions, respectively)
Kobayashi et al. 2010. Sensors.
34
Is spicy a taste?
• Spice has been argued to be more of a tactile
sensation (heat or pain) than a taste
• Linked to chemicals found in spicy foods, including
capsaicinoids
• Capsaicinoids activate transient receptor
potential cation channel subfamily V
member 1 (TRPV1) receptors
• Found on the tongue and other regions of the body
35
TRPV1 receptors and heat
• The heat of foods is
measured in Scoville
units
• The higher the rating,
the spicier the food
• Extracts from foods
with high ratings more
strongly activate
TRPV1 receptors
1. Caterina et al. 1997. Nature.
36
Why do we love hot food?
• Genetic factors
• Personality factors (sensation-seeking)
• Social factors (desire to impress, look tough)
• Prior positive experiences (adaptation is significant:
the more you eat, the more you can tolerate)
• The ‘endorphin hypothesis’ not strongly supported
1.
2.
3.
Tornwall et al. 2012. Physiol Behav.
Ludy and Mattes. 2012. Appetite.
Byrnes and Hayes. 2013. FQP.
37
The Taste Pathway
• Taste cells > Bipolar neurons > Cranial nerves (7, 9,
10) > Brainstem Structures > VPM Thalamus > Primary
Gustatory Cortex (Insula)
From the insula, inputs might
be sent to the secondary
olfactory cortex (OFC)
38
Neural Basis of Super-tasting
• Variations in taste, particularly for bitter taste, are
associated with the gustin gene (for a salivary trophic
factor) + TAS2R38 gene (for a bitter taste receptor)
• People with certain TAS2R38 alleles are very sensitive
to (revolted by) particular bitter tastes
• propylthiouracil (PROP) + phenylthiocarbamide (PTC)
• Though many believe that super-tasting is associated
with taste bud number (specifically fungiform papillae),1
this claim has been vigorously challenged2
1. Melis et al. 2013. PLoS One.
2. Galo et al. 2011. Physiol Behav.
3 Garneau et al. 2014. Front Int Neurosci.
39
Taste Hypotheses
Taste Map Theory
Definitely disproven
(you can disprove this
yourself, RIGHT NOW)
Supertaster Bud Theory
Currently debated
(Jury is still out)
40
‘Gustotopic’ mapping – Sweet taste
41
Gustotopic mapping – Sweet/Bitter
• Cortical areas representing taste can be stimulated
• Stimulating ‘sweet’ regions causes chamber
preferences whereas stimulating ‘bitter’ regions causes
chamber aversions
42
Summary
• Sensitivity varies for tastes, highest for bitterness
• Sensitivity varies between individuals
• Genes and taste bud organization may be involved
• Gustotopic mapping to an extent
• Evidence for Sweet and Bitter, Sour is more complicated
• Far less established
• Intersection of gustatory and olfactory pathways
• Taste is complicated
43
Part 2C: Touch and Pain
44
Sensory receptors in the skin
Different receptors adapt at different rates to stimulation.
Fine touch is fast, for instance, whereas pain is slow!
45
Touch: from Start to Finish
46
Pathways in the SC
• Sensory pathways transmit information from the
periphery to the brain via the SC (afferent)
• Motor pathways transmit information from the brain to
the periphery via the SC (efferent) (L05)
47
Columns of the SC
48
Sensory Pathways “cross over”
Posterior Column – Medial Lemniscus
Pathway (Fine Touch, Pressure)
Anterior Spinothalamic Pathway
(Pain + Temperature)
49
Unilateral SC lesion
• This interesting pattern of
decussation has some
important implications
• Unilateral SC lesions
(affecting one side of the
SC) result in:
• ipsilateral loss of fine touch
+ pressure sensation
• contralateral loss of pain +
temperature sensation
50
SC reflexes
Sensory input (patellar tendon tap stretching the
quadriceps muscle) can drive non-voluntary motor
movement (subsequent quadriceps extension).
51
Sensory Pathways
Posterior Column – Medial Lemniscus
Pathway (Fine Touch, Pressure)
Anterior Spinothalamic Pathway
(Pain + Temperature)
52
Somatotopic representation
53
Related to touch, we have
pain.
54
What is pain?
• A feeling resulting from
injury
• Linked to the healing
process
• Can be studied relatively
easily
• A feeling that injury has
occurred
• Can extend beyond the
healing process
• Private experience; difficult to
study objectively
55
What is pain?
Adaptive response, allowing us to identify danger +
withdraw1
1. Dawkins. 2010. The Greatest Show on Earth.
2. Bourinet et al. 2014. Physiol Rev.
56
Insensitivity to Pain
• Serious condition
• High frequency of injury and
early death rate
• Injuries progress significantly
and become severe before
being noticed
• Extraordinary vigilance is
required
57
Sensory Pathways
Posterior Column – Medial Lemniscus
Pathway (Fine Touch, Pressure)
Anterior Spinothalamic Pathway
(Pain + Temperature)
58
Pain network
• Involves Prefrontal cortex (PFC), Anterior Cingulate
Cortex (ACC), Insula + Somatosensory Cortex (S1, S2)
59
Individual Differences in Pain
Individual differences in pain are correlated with
differences in the activity of the PFC, ACC and SS
cortex.
Coghill et al. 2003. PNAS.
60
What would happen to
cortical representation of
touch if you LOST a body
part (e.g. amputation)?
61
How do you respond to pain?
• One of the most common approaches is to rub the
affected area (though this is not always beneficial)
• Why might this help?
• One possibility is that transmission of touch information
modulates transmission of nociceptive information
62
Gate Control Theory of Pain
63
Modulation of Pain
• There are other mechanisms by which the
transmission of nociceptive information is modulated
• Dorsal horn neurons in the SC are also modulated by
descending inputs from other brain regions to the SC
• The periaqueductal gray (PAG) and rostroventral
medulla (RVM) are two brain areas that contribute to
the descending modulation of nociceptive information
64
Pain pathways
• Nociceptive information is
transmitted from the
periphery to the brain via the
ascending spinothalamic
tract
• However, this system is
modulated by descending
inputs
• In particular, the PAG/RVM
may be vital
65
Implications – Pharmacology
• Inhibitory interneurons
in this pathway express
μ-opioid receptors
• Opioids (e.g. morphine)
bind to these receptors
• Turning off these
inhibitory neurons with
opioids may relieve
pain
66
Part 2D: Hearing (=
Auditory function)
67
Sound waves and hearing
• Sounds are perceived differently because the waves
involved have different physical characteristics
68
Sounds are Complex
69
Fundamental Frequency
• Most sounds involve multiple waves
• e.g. 50, 100, 150 + 200 Hz
• How do we perceive pitch in such a case?
• You perceive the pitch that is related to the greatest
common divisor
• For the combination of waves above, 50 Hz
• This is called the Fundamental frequency
• Intriguingly, sometimes the fundamental frequency is
not even present in the combination of waves
• e.g. For 200, 300 + 400 Hz waves, the fundamental
frequency is 100 Hz (missing fundamental)

70
We might ‘perceive’ a
sound that is not there!
71
Auditory Range (Hz) in Humans
Range
varies by
species
72
The Auditory Pathway
73
Tonotopic mapping
• Different frequencies, different regions of the cortex
74
Hearing loss
• Conductive hearing loss is caused by outer ear
damage (e.g. eardrums or ossicles)
• Sensorineural hearing loss is caused by damage to
the cilia or auditory nerve
• Cilia are lost with age; ~40% gone by age 65
• With aging, we lose sensitivity to high-pitched sounds
• Loud sounds (> 85 dB) can damage hearing
• Sounds > 130 dB are dangerous (painful, even)
75
Change in hearing with age
CLIP: https://www.youtube.com/watch?v=yDiXQl7grPQ
76
Aids + implants
• Hearing aids amplify signals
• If hair cells in the cochlea are damaged/lost, hearing
aids will be less effective – we need alternatives
• Cochlear implants bypass the cochlea, stimulating the
nerve directly
77
Sound localization
• Differences in signals received by the left and right ear
are useful in making determinations (interaural)
• Inferior colliculus plays an important role
78
Sound localization
• In certain species, the ears are asymmetrical; this can
improve sound localization
79
Part 2E: Vision
80
Vision begins with Light
• Light can be viewed as electromagnetic wave
• Light waves vary in wavelength ()
• We can only see certain wavelengths (visible
spectrum; ~700 to 400 nm)
81
Photoreceptors
• Light affects photoreceptors (rods + cones) in the eye
82
Photoreceptors (Rods + Cones)
• Rods function well in low light and are used in night
vision (scotopic conditions)
• Species active during the night have more rods
• Cones function well in light (during phototopic
conditions) and are responsible for high acuity and
color vision
• Species active during the day have more cones
• Dysfunction of cones plays a role in color blindness
• Organization of rods + cones varies across the retina
83
Cones differ in Light Sensitivity
Different types of cones may contribute to color
perception.
84
Visual pathway
85
Retinotopic mapping
• Different visual field region, different cortical region
86
There are many cases
where your perception of
a color associated with a
certain wavelength can
change.
87
Spectral Sensitivity Curve
• A graph of the perceived brightness of the same
wavelength of light presented under two conditions
• Scotopic (low light intensity/dark, primarily rods)
• Photopic (high light intensity/bright, primarily cones)
In the dark, BLUE
looks brighter than
yellow
In the light,
YELLOW looks
brighter than blue
88
Color Constancy
• The subjective perception of a color remains constant
under varying illumination conditions
• Your visual system ‘adjusts’ your perception of color in
a scene based on the perceived illumination of that
scene (‘subtracts the illumination of that scene’)
89
Dress Illusion
• Note how the light in the background plays a role in
your perception of the color
90
Contrast enhancement
• Affects our edge perception
91
Lateral inhibition (mechanism)
• Cells exposed to different
light intensity
• Intense for A – D
• Dim for E – H
• Firing rate proportional to
light intensity
• High for A – D
• Low for E – H
• Cells inhibit their
neighbours
E weakly
inhibits D
D strongly
inhibits E
• Strong inhib from A – D
• Weak inhib from E – H
92
Feature Detection Neurons
93
Detecting movement
• Cells have receptive fields for movement
• Several cells converge their input on downstream
targets
94
What do we do with visual
input?
95
Next…
• Information processed is
sent outward to guide other
behaviors
• The dorsal stream is
involved in vision-guided
action
• The ventral stream is
involved in vision-guided
object recognition
(conscious awareness)
96
When visual input is
changed, how does the
visual cortex reorganize?
97
Blindfolding + VC activity
98
In blindness
• In blindness, there is no awareness of visual stimuli
• Does this mean that the visual cortex is no longer
doing anything?
• Reorganization can occur, with neurons being
reallocated to other functions – like reading braille
(tactile writing system for the visually impaired)
99
Reorganization of the Visual Cortex
• In blind individuals, there is increased responsiveness
of the lateral occipital cortex and medial occipital cortex
to language (note the limited effect for music)
100
Part 3: Multi-sensory
Integration
101
Taste is a great example
102
The McGurk Effect

103
Intersection between the senses
• Our perception of sound is influenced by visual
information (intersection of hearing + vision)
• This is not just an illusion but an important part of how
we communicate on a daily basis
• Many people feel they can listen better when they are
watching someone (“I see what you are saying”)
• A similar effect may be involved in speech-reading/lipreading; visual inputs may be used to activate the
auditory cortex, facilitating speech parsing1
Bourguignon et al. 2020. J Neurosci.
104
Speechreading
• Involves frontal areas (including those for speech
articulation), occipital areas (for vision) and temporal
areas (for language, hearing and sensory integration)
• Particularly important is the superior temporal sulcus
(STS), a key site for multi-sensory integration
105
Interactions between Senses
• Blending of different sensory modalities (synesthesia)
can occur (e.g. tasting colors)
• Difficult to estimate frequency; mild forms may not be
reported because individuals do not feel it is abnormal
or a problem
106
Color – Grapheme Synesthesia
• Words have an associated color
• What are some implications of this effect?
107
White matter in Synesthesia
• Assessed with diffusion tensor imaging (DTI)
• Greater connectivity in right inferior temporal cortex
and left parietal cortex
• Significance unclear
108
Competition between the Senses
109
1- Explain the change in neurotransmitter levels that often occurs in:
a. Parkinson’s Disease (1)
b. Alzheimer’s Disease (2)
c. Depression (2)
2- A. You have two extraordinary but completely different experiences that are only
hours apart. For the rest of your life, recalling one of these experiences leads you to
recall the other. Any change in your memory for one experience also leads to a change
in the other memory. Explain, using information from the course, why this interesting
event might occur. (2)
B. How do we induce LTP in the hippocampus? Why do we use this method? (2)
C. Give an example of a presynaptic form of LTP. (1)
3- A. Explain the change that occurs in neuron number and synapse number from the
first years of life to early adulthood. (2)
B. Explain the biological mechanisms behind the change you described in A). (2)
C. Explain why the change you described in A) might be advantageous for the organism.
(1)
4- Discuss the potential use of technology to treat:
a. Parkinson’s Disease (2)
b. Depression (2)
c. Paralysis (3)
d. Memory loss (3)
In your answer, make sure to discuss why the treatment will work as well as its
limitations.
5A. Why don’t severed axons regrow in the CNS? (2)
B. A person has a brain injury to their visual system in adulthood. Via a new
experimental treatment, you add a large population of immature neurons to their brain
in the areas where neurons have been lost. Unfortunately, the treatment fails to restore
vision. Explain a very likely reason why the new neurons do not behave like the older
neurons. (2)
C. Explain how a neuron may switch its phenotype depending upon the environment in
which it resides. (1)
6- Define the following terms in one or two sentences each:
A. Mirror neurons
B. Ipsilateral
C. Hypofrontality
D. Critical period
E. CREB
F. Place cell
G. Biomarker
H. Jitteriness Syndrome
I. Comorbidity
J. Reticulospinal tract
7-
1- Explain the change in neurotransmitter levels that often occurs in:
a. Parkinson’s Disease (1)
b. Alzheimer’s Disease (2)
c. Depression (2)
2- A. You have two extraordinary but completely different experiences that are only
hours apart. For the rest of your life, recalling one of these experiences leads you to
recall the other. Any change in your memory for one experience also leads to a change in
the other memory. Explain, using information from the course, why this interesting event
might occur. (2)
B. How do we induce LTP in the hippocampus? Why do we use this method? (2)
C. Give an example of a presynaptic form of LTP. (1)
3- A. Explain the change that occurs in neuron number and synapse number from the
first years of life to early adulthood. (2)
B. Explain the biological mechanisms behind the change you described in A). (2)
C. Explain why the change you described in A) might be advantageous for the organism.
(1)
4- Discuss the potential use of technology to treat:
a. Parkinson’s Disease (2)
b. Depression (2)
c. Paralysis (3)
d. Memory loss (3)
In your answer, make sure to discuss why the treatment will work as well as its
limitations.
5A. Why don’t severed axons regrow in the CNS? (2)
B. A person has a brain injury to their visual system in adulthood. Via a new experimental
treatment, you add a large population of immature neurons to their brain in the areas
where neurons have been lost. Unfortunately, the treatment fails to restore vision.
Explain a very likely reason why the new neurons do not behave like the older neurons.
(2)
C. Explain how a neuron may switch its phenotype depending upon the environment in
which it resides. (1)
6- Define the following terms in one or two sentences each:
A. Mirror neurons
B. Ipsilateral
C. Hypofrontality
D. Critical period
E. CREB
F. Place cell
G. Biomarker
H. Jitteriness Syndrome
I. Comorbidity
J. Reticulospinal tract

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