Weeks 1-4 Behavioural Neuroscience

What is behavioral neuroscience?

Also called biological psychology

Biology:

Study of living processes (how living things do things)

There is quite a bit of biology in this course

Refer to Appendix A

Psychology

Study of behavior

How behavior is created, modulated, which ones we have

The study of the biological processes by which the body and in turn the brain generates and controls behavior

How does the body create and control behavior?

We will primarily discuss the brain, not other aspects of the body

How our nervous system creates behavior

Assumptions

Behavior is generated by the nervous system

The mind is embodied in/by the brain

Deeper assumption

Behavior is almost entirely the result of the patterns of activation within the brain (different areas will ‘light up’ in different ways = different actions)

The activity in the brain when you see a rabbit is your perception of a rabbit

You don't control your brain, your brain is you

In this course, we will behave as if these things are true despite individual beliefs

Challenges

Neurons are too small and fast to see (a lot smaller than the thickness of a sheet of paper)

When a neuron fires (has an action potential), it takes 1-2 milliseconds

There are about 80 billion of them (in a human); 10x the population of the planet

They are in a network

A single neuron doesn't do much, but several connected neurons in a network start doing really exciting things

We’re using them!

Even small amounts of damage to the brain will cause serious impairments

We can't just ‘remove’ some

Key methods

Psychopharmacology

Giving people drugs

Psychoactive drugs to change what your brain is doing

Many drugs mimic already existing chemicals in the brain

Measuring and recording

MRI and fMRI

Lying down in a big machine

EEG and MEG

Electrodes

DTI

Diffusor Tensor Imaging

Show connections between parts of the brain to trace them

Studying brain-damaged patients

Seeing how the brain functions when a part of the brain is missing

Issue is that each person damages the brain in a different, unique way

Comparative cognition

Comparing across species

This allows us to do things that would be unethical to humans

Tinbergen’s four questions

Mechanism (physiology)

Explain the processes that control the behavior

Discussed mostly in the course

Ontogeny (development)

Explain how the behavior develops or matures

Phylogeny (evolution)

Explain the steps by which the behavior evolved

Functional (adaptive)

Explain the adaptive benefits of the behavior, what is it for

Evolution basics

Natural selection:

More offspring are born than can survive

More animals around than food for (competition for survival)

There is heritable variations between individuals

Inherit things from their parents

Individuals can’t all be the same

Individuals better adapted to their environment have higher fitness -> more surviving offspring

If we evolved along with the other animals, then there would be a mental (psychological) continuity as well as a physical one

By studying animal behavior (psychology), we can learn about human behavioral mechanisms

Ethics

Is it ethical to use non-human animals in research?

Animals cannot give (informed) consent

There is a lot of debate on this question

Textbook, introduction

In Canada (and most other places) there are rules

‘Animals Ethics Module’ under recommended readings

Evolution of behavior

Is behavior heritable?

Tryon’s maze-bright/ maze-dull experiment:

Group of rats are tested on a maze (to find food) and then are counted for how many mistakes they make

Best and worst bred together; took their offspring and ran them through the maze

This shows that performance can be heritable!

January 11th

Evolution of the brain

When we do this comparison, we have to consider the sizes of the different brains

The proper way to do this comparison is to compare the sizes of the bodies of the different mammals

The graph compares body weight and brain weight

Which animals have a larger brain relative to their body size?

Humans are way above the line

My, what a big brain!

Do big brains make you smarter?

Men have larger brains but not a higher IQ

Larger bodies on average

No correlation between brain size and IQ

Reasons NOT to have a big brain:

Brain tissue is expensive (uses a lot of energy)

Only consumes glucose (and oxygen), and lots of it

We need lots of oxygen to keep our brains and bodies working

We eat a lot

Delicate. Needs protection -> big, heavy skull

Very easy to damage

Grows little after birth -> large heads on babies

Difficulties giving birth

The rate of death in childbirth was very high because of this

Requires lots of maintenance

Example: clearing away dead neurons

We require a lot of sleep to recharge

TED talk (recommended readings)

Cells of the brain

Neurons

Not all the same, but share many similar functions

There are many shapes and sizes

Sensory, motor, interneuron (intrinsic)

Pyramidal, Purkinje, spindle, Golgi

Glia

Very mysterious

Astrocytes, oligodendrocytes, Schwann cells, microglia, radial glia

Comes from the root word ‘glue’

We don’t know much about them but they do a lot of work in the brain

Equal parts glia and neurons in the brain

Glia can turn into neurons (but not the other way around)

Blood vessels

Blood brain barrier

Separated from the brain to protect the brain

Visualizing cells

Staining technique discovered by Golgi (the Golgi stain), improved by Cajal

Standard method

Randomly stains only 3% of neurons (there is no empty space that looks like in the picture)

Nucleus: where everything lives

Axon: thin filament extending from the soma (cell body), neurons only have one

Bouton: axon splits, where the branches end

Oligodendrocytes (inside the CNS) or Schwann cells (outside the CNS) (glia): wrap themselves around the axon, produce myelin

Rode of ranvier: gaps between the glia

Dendrite: extensions of the soma

Moves in one direction only: left to right (from the dendrites to the axon terminal)

Synapse: the point where two neurons connect to each other (the key to how neurons function)

The neuron the information is coming from is the presynaptic neuron

The neuron the information is received is the postsynaptic neuron

Dendrites have spines

Allow us to introduce the fact that our brain is constantly changing

The average dendritic spine lasts approximately a week

Synapses:

Terminals that attach to postsynaptic neurons’ dendritic spines or soma

Can be excitatory or inhibitory

Synapse types

Excitatory

When the presynaptic cell fires, the postsynaptic cell becomes more likely to fire

Inhibitory

When the presynaptic cell fires, the postsynaptic cell becomes less likely to fire

Types of neurons

Sensory

Convey signals from sense organs to brain

Soma on a separate stalk, near middle of axon

Dendrites near or at the sense organ

Synapses in the spinal cord (mostly)

Very long (up to several meters)

Such as a giraffe

Motor

Convey signals from the brain to muscles

Soma and dendrites in or near spinal cord

Synapses at the muscle

Neuro-muscular junction

Also very long

Interneuron (intrinsic neuron)

All within one brain (or spinal cord) structure

Usually very short

Often inhibitory

Axons are

Afferent: entering a structure (arriving)

Efferent: exiting a structure

Every axon is both afferent and efferent to somewhere

Basic biology/chemistry

Cells have semi-permeable membranes (some things can get through, some cannot)

Protein channels are embedded in the membrane

Some channels are specific (only let certain things in and out of the cell)

Can be open or closed (can change their shape so the channel can become blocked )

Inside and outside the cell have ions (floating around the cell):

A charged particle that can be positive or negative

The cell membrane doesn't really like charged things

Sodium (Na+)

Potassium (K+)

Calcium (Ca+2)

Chloride (Cl-)

Ions move down gradients

Concentration (diffusion): ‘want’ to move to where there are less of them (spread out evenly everywhere)

Ions are charged particles

Electrical: ‘want’ to move to where the charge is opposite (positive ions want to move where there are negative ions)

Sodium-potassium pump

Active (energetic) transport of

Sodium (Na+) out of the cell

Potassium (K+) into the cell

More Na+ out than K+ in (3:2)

Causes a concentration gradient:

K+ ions ‘want’ to leave (because most of them are inside)

Na+ ions ‘want’ to enter (because most of them are outside)

Runs all of the time and pretty fast

Resting potential

Membrane does not let most ions through

K+ channels partly open; Na+ channels closed

There is a charge across the membrane (membrane potential)

Inside of cell is negatively charged:

Na+/K+ pump is running (3:2)

Cell contains negative proteins

Resting potential for most is approximately -65 mV

Ions face gradients:

Na+ ions:

Concentration gradient: in

Electrical gradient: in

Really wants into the cell

K+ ions:

Concentration gradient: out

Wants to leave the cell

Electrical gradient: in

Also positively charged which tells them they want into the cell

Ion channels

Three key types:

Na+/K+ pump: active (requires energy)

K+ channels: partly open during resting potential

Na+ channels: closed during resting potential

Can close in 2 different ways

Activation gate

Inactivation gate

Channels can be voltage-gated

The voltage across the membrane can open or close the channel

By changing the voltage will determine if it’s opened or closed

The Na+ and K+ channels are voltage-gated

Voltage-gating

Cell is resting at about -65 mV

External stimulation (later) makes it less negative

Depolarization

Channels open/close:

K+ channels:

Partly closed at resting potential

Open at high voltages

Na+ channels:

Activation gate:

Closed at resting potential

Open at higher voltages

Inactivation gate:

Open at resting potential

Closes at very high voltages

Action potential

Cell has a threshold

Depolarization below threshold dies out

Depolarization above threshold leads to:

Voltage-gated Na+ channels open

Na+ floods in

Voltage rises, fast

Na+ channels close; K+ channels open

K+ channels and pump restore resting voltage

Most K+ channels close

Refractory period

The inactivation is slow

At resting potential, the inactivation gate is open

Once at the peak and the inactivation gate slams such, the neuron can no longer become excited

When neurons can’t be excited, it is in its refractory period (at rest)

Immediately after a neuron has an action potential, they can’t have another one right away because the activation gate is still closed (they are slow); it’s in its refractory period which varies from neuron to neuron

Action potential propagation

Propagation = multiplying or replicating

The purple area is when the neuron is having an action potential (sodium is coming in through open channels)

Ions like to move down their gradients

Sodium will move left and right inside the membrane (which makes the membrane less negative becoming depolarized)

This opens those channels which allows sodium to enter at point 2

Propagation: the party analogy

House 1 is having a party

Front door (Na+ channels) open for guests

Guests in back yard spill over into house 2’s yard

Diffusion of Na+ ions inside axon

House 2 decides to have a party too (depolarization)

They open their door (Na+ channels)

House 1 residents get tired, go to bed, lock the doors (inactivation gate)

Na+ channels inactivated; refractory period

Party in house 2’s yard spills over to house 3

But not to house 1, since their doors are locked

Party moves down the street

Myelin

Exuded by Schwann cells (PNS) or oligodendrocytes (CNS)

Covers the axon, except Nodes of Ranvier

Enables faster saltatory conduction

Jumping action potential across Nodes of Ranvier

This process is faster

Party analogy

House 2 abandoned

Guests from #1 cross #2’s yard to #3

No need to wait for house #2’s party to get going and only then move to #3

EPSPs and IPSPs

Testing neuronal communication:

Stimulate presynaptic axon

Measure from postsynaptic soma

Results:

At an excitatory synapse:

Excitatory Postsynaptic Potential (EPSP)

At an inhibitory synapse:

Inhibitory Postsynaptic Potential (IPSP)

Becoming even more polarized (hyperpolarized)

EPSP and IPSP mechanism

EPSP are usually too weak to cause an action potential

Cell returns to resting potential

EPSP:

Depolarization causes some Na+ channels to open

Some Na+ enters but not enough to open more voltage-gated Na+ channels

Channels close when stimulation ends

Na+/K+ pump restores resting potential

IPSP:

Stimulation opens K+ or Cl- channels

K+ leaves or Cl- enters; cell hyperpolarizes

Channels close when stimulation ends

Cl- diffuses out; Na+/K+ pump helps

Temporal summation

Multiple EPSPs arriving soon after each other

EPSP 1 arrives; cell depolarizes slightly

Cell begins to repolarize

EPSP 2 arrives; cell depolarizes to higher voltage

If summed EPSPs exceed cell threshold:

Cell polarization high enough to open Na+ channels

Action potential

EPSPs can also sum with IPSPs

One neuron firing multiple times

Spatial summation

EPSPs arriving at the same time from different synapses (different axons)

Not necessarily from the same presynaptic neuron

Multiple neurons firing at the one time

Response specificity

Make a neuron that only responds to light moving in one direction

Figure 2.1 (textbook)

The long tail is a dendrite

Rate of firing

Most neurons have a spontaneous firing rate

Fire with no external stimulation

At a constant rate (more or less)

Synapses are not only on/off

Can fire at different rates

Rate of firing can be part of the message

IPSPs can decrease the rate of firing

EPSPs can increase the rate of firing

Control mechanisms in the brain

Almost all behaviors result from

Communication between neurons

[+ the mysterious role of glia]

Brains need to do many different things

See, run, throw things, dream, speak, play the violin

Control mechanisms (examples so far)

excitatory/inhibitory neurons in complex circuits

More/less dendritic spines

Different activation thresholds

Different numbers of ion channels

Different spontaneous rates/changes in rate

Differences at the synapse

Synapses

Where the action is!

Connections between neurons

Presynaptic neuron -> axon terminal (bouton)

Postsynaptic neuron -> dendrite or soma

Requires a different form of communication

Chemical (not electric)

[there are also electrical synapses]

Structure of the synapse

Pre- and postsynaptic cells do not touch

Presynaptic cell releases a chemical (neurotransmitters) that affect the postsynaptic cell

The importance of glia

Most synapses are wrapped in astrocyte (a type of glia) processes

Prevents the neurotransmitter from spilling everywhere (they also play an active role in communication)

Coordinate activity from many different synapses

Overview of synaptic transmission

Neurotransmitter synthesized

Action potential arrives

Voltage-gated Ca+ channels open; Ca+ enters

Neurotransmitters released into synaptic cleft

Transmitter molecules attach to postsynaptic receptors (receive the neurotransmitter)

This does two things:

Ligand-gated ion channels open (have a pore which stuff can get in or out; can be open or closed)

Ligand-gated = opens due to the binding of a protein; attaches to something else

Depolarization of postsynaptic cell OR

G-protein receptors activate downstream pathways (not ion channels)

Enzymes in postsynaptic soma cause depolarization

The action potential arrives…

Action potential moves down axon

At terminal bulb (bouton), depolarization opens voltage-gated Ca+ channels:

Ca+ enters cell

Vesicles (bags of membrane) containing neurotransmitter fuse with membrane

Neurotransmitter spills out into synaptic cleft

Vesicles then get recycled (sucked back out of the cell membrane) and refill it with neurotransmitter

There are lots of vesicles

Only a small fraction releases at each event

They don't all get released at one time

Ionotropic receptors

Are ion channels

Ligand-gated: binding the neurotransmitters opens them

Channel usually admits:

Positive ions (Na+, K+, Ca+; excitatory): glutamate

Cl- (inhibitory): GABA

Neurotransmitter detaching closes channel

Channel opening allows ions into postsynaptic cell, directly depolarizes it

Fast (1ms from binding to opening)

Short-lasting (5ms to closing)

Metabotropic receptors

Are G-protein coupled proteins (attached to the G-proteins)

Activated by binding of neurotransmitter

Some will move down the cell, causing other proteins to start/stop acting

May cause structural changes in the cell

Cause lots of downstream effects inside the cell

Enzymes inside the cell open ion channels

Ions enter, depolarize cell

Lots of different neurotransmitters:

Dopamine, serotonin

Slow (30 ms from binding to opening)

Long-lasting (few seconds; up to many years)

Reuptake

Neurotransmitter left in the synaptic cleft

Would reactivate receptors if left there

Needs to be removed or ‘recycled’

Broken down (e.g. acetylcholine, by the receptor)

Presynaptic cells reabsorb it (sucks it back in)

Reuptake

Active transport channels (transporters)

Astrocytes (and other glia?) absorb transmitter

Need for speed

Synapses need to be fast

Sensory information has to be acted on quickly

Lots of synapses (100-500 trillion)

Vesicles wait in the active area

Ca+ fuses the vesicle directly

Synaptic cleft is small (20-30 nm)

Diffusion takes 0.01 ms

Ionotropic receptors

Depolarize the postsynaptic cell immediately

Neuronal communication

Cell A:

Action potential (depolarization) moves down axon

Reaches bouton. Voltage-gated Ca+ channels open

Ca+ enters the cell, activating the vesicles

Vesicles fuse with cell membrane

Neurotransmitter spills into synaptic cleft

Diffuses across synaptic cleft

Cell B:

Receptors bind neurotransmitter

Binding changes shape of protein; channel opens

Ions enter the cell. Depolarize cell (EPSP)

More EPSPs (temporal or spatial) increase depolarization

Cell B has an action potential, which moves down the axon

Neurotransmitter types

Amino acids: glutamate, GABA, glycine, aspartate

Monoamines: dopamine, serotonin, noradrenaline

Peptides: opioids, substance P, endorphins

Mostly act to modulate synaptic receptors

Over 100 types currently known

Others: acetylcholine, anandamide, oxytocin

Neurotransmitter actions

Many brain regions mostly use one transmitter

Dopamine

Associated with reward (nucleus accumbens) and movement (substantia nigra)

Being happy means having an active nucleus accumbens (your nucleus accumbens IS you)

Serotonin (5-HT)

Regulates mood, sleep and other long-term changes

Raphe nuclei, hippocampus

Acetylcholine

Movement (neuromuscular junction)

Chemical interactions

Neurotransmitters bind to receptors

Affinity: how strongly chemical binds to the receptor

Efficacy: how strongly chemical activates the receptor

Other chemicals can bind to the same receptors

Agonists: mimic the action of the transmitter (bind and activate the same way the receptor would)

Endogenous ligand

Antagonists: block the transmitter from binding; does not activate the receptor

January 25th

Possible drug mechanisms

Psychoactive (have an effect on the brain)

Use drugs to figure out why the brain does what it does

Bind to postsynaptic receptors

Agonists or antagonists; varying affinities and efficacies

‘Dirty drugs’- bind to many different things

Affect neurotransmitter synthesis

Increase/decrease amount of precursor

Degrade transmitter (break down transmitters)

Causes vesicle leakage (incontinent)- constantly sending out a low-grade message

Break down transmitter in synaptic cleft

Block transmitter reuptake

Sucks back up into it

SSRI (selective serotonin reuptake inhibitor)- causing more serotonin to hang around the synapse

Receptor types

Ionotropic/metabotropic

Excitatory/inhibitory

Often consist of subunits

May be unevenly distributed in brain regions

Dopamine D1, D2

Different subunits may bind slightly different to different drugs

GABA receptor

20 subunit types

Benzodiazepine (Valium) binding site varies in affinity

GABA receptors

GABA is the most common inhibitory neurotransmitter

Has 2 different receptors:

GABAa receptors:

Ionotropic

Allow Cl- ions to enter the postsynaptic cell when open

Subtype (GABAc) made of all p (rho) subunits [in the retina]

GABAb receptors:

Metabotropic

Mediate long-term inhibitory effects

Proteins affected eventually open K+ channels

Distribution of dopamine receptor subtypes

Emphasizes the different dopamine subunits

A few examples

Selective serotonin reuptake inhibitors (SSRI)

Prevent reuptake of serotonin

More serotonin left in synaptic cleft for longer

Over-stimulation of postsynaptic cells

Function as antidepressants (Prozac, Paxil, Zoloft)

Retrograde messengers

THC: binds to cannabinoid receptors (for anandamide; ‘bliss’) on the presynaptic neuron

Anandamide is a retrograde messenger (it goes backwards, opposite of normal neuron communication)

Prevents release of further neurotransmitter

Contextual effects

Heroin (= morphine, fentanyl): opioid receptor agonist

Long-term, cells decrease number of receptors (the brain will just shut down the receptors)

Tolerance and withdrawal effects

Taking the drug in a new place can cause overdose (conditioned tolerance)

Long-term effects

Receptors become less/more sensitive

Nicotine: increases dopamine release (like cocaine)

Long term exposure sensitizes to the receptors

Morphine: high affinity agonist of opioid receptors

Receptors become less sensitive, are decoupled from their G-proteins, or are sucked into the cell

Dosage-dependent effects

MDMA increases the release of dopamine at low doses, and serotonin as well at high doses

Alcohol at increasing doses: euphoria, lethargy, memory loss, confusion, coma

Brain orientation

Directions:

Dorsal: (towards back) top

Ventral: (towards belly) bottom; ventilation

Anterior: front

Posterior: back

Medial: towards the middle

Lateral: towards the side

Planes:

Horizontal: across the eyes

Sagittal: down the nose

Coronal: down the ears

Tissues

Brain has two kinds of matter:

Gray matter: somas (and dendrites)

White matter: axons

Sometimes organized in tracts:

Bundles of axons

Peripheral nervous system (PNS)

Everything except brain and spinal cord

Somatic nervous system

Transmits messages to/from the brain

Sensory, motor neurons

Autonomic nervous system

Operates automatically, without conscious control

Connects rest of body to spinal cord

Sympathetic

Increased activation; fight or flight

Parasympathetic

Decreased activation, rest and digest

Spinal cord

Part of the central nervous system (CNS)

Communicates with the brain

Mostly controls and coordinated movement

Parts of the brain

The spinal cord is part of your brain

Hindbrain

Medulla

Pons

Cerebellum (the red part that is the lump at the back)

Contains more neurons than in your entire brain put together

Midbrain

Colliculi

Tegmentum

Movement and senses

Forebrain (most of the human brain)

Limbic system

Hippocampus

Amygdala

Thalamus, hypothalamus

Cerebral cortex

Frontal

Temporal

Central

Parietal

Occipital

Hemispheres

Cortex (and most of the rest of the brain) is symmetrical

Left and right hemispheres

Most (cortical) structures exist in both hemispheres

Connected by corpus callosum (and other, smaller, structures)

Many functions are lateralized (focus on one side of the brain)

Spinal cord

Part of the central nervous system (CNS)

Communicates with the brain

Controls and coordinates movement (mostly)

Hindbrain

Medulla oblongata

Top of the spinal cord; thicker and contains cranial nerves

Pons

‘Bridge’

Crossover of axons between hemispheres

Usually between the midbrain and the hindbrain

Cerebellum

Contains more neurons than the rest of the brain combined

Control of movement (including shifting attention)

Thalamus and hypothalamus

Thalamus

Most sensory information going to the cortex (except smell)

Each sensory modality has a dedicated thalamic nucleus

Functions like a ‘switchboard’

Involved in combining information from different senses

Involved in attention regulation:

Cortex sends some signal back

Some stimuli are processed more

Hypothalamus

Regulates hormonal release

Mostly from the pituitary

Involved in motivation, metabolism, hunger, sleep…

Limbic system

Hippocampus

Involved in memory formation and relaying different pieces of information to each other

Amygdala

Involved in emotion regulation, memory strength, decision making, attention

Cingulate gyrus

Involved in motivation, learning

Connects the other parts of the limbic system

Brain control

What does it mean that area x of the brain controls behavior y?

E.g. cerebellum coordinates movement

So does the spinal cord

Damage: has effects on attention, language, fear, mental imaging

Schizophrenic patients have reduced Purkinje cell density

Connections: prefrontal cortex, limbic system, brainstem, thalamus

It is important to remember that what your brain does gets divided into separate tasks, but one area doesn't just control one other thing (it is all related)

The cortex

‘Folded’ part (in humans)

Cortex has a larger % of brain in mammals than humans do

Divided into hemispheres

Each side of the body is controlled by the opposite (contralateral) side of the brain

‘All’ the information crosses over

Layers and columns

Neurons in the cortex are organized

Vertically (dorso-ventrally) into layers (laminae)

Different layers have different cell types

Different layers have different connections

In most regions there are 6 layers (in humans)

Horizontally (fronto-parietally) into columns

Cells in the same column react to the same stimuli

[Sometimes] nearby columns react to similar things (e.g. tonotopic arrangement)

Major subdivisions

4 lobes:

Frontal (in the front)

Parietal (in the back)

Occipital (at the very back)

Temporal (at the sides)

E.g. medial temporal lobe

Localized functions

Somatosensory and motor cortices are adjacent

Each contains a map of the (contralateral) body

Primary touch areas (fingers, tongue) are overrepresented

[slight differences between motor and sensory]

Different strengths of stimulation are represented separately (4 copies in each cortices)

Plasticity in the cortex

The ‘maps’ are not fixed

Can recover in case of injury

Can change as a result of learning

Parietal lobe

Somatosensory cortex

Involved in proprioception

The sense of where the parts of our body are

Involved in locating and identifying objects

Involved in the binding of stimuli

How do we know that a visual image and a sound are parts of the same object in the world?

Binding problem

When this goes wrong

Senses ‘bleed into’ each other; synaesthesia

Temporal lobe

Auditory processing

Memory and learning

Language

Occipital lobe

Deeply involved in vision

Frontal lobe

Involved in many complex cognitive tasks

Involved in working memory

Prefrontal cortex:

Involved in ‘executive function’

Tying together information from all over the brain

Inhibits much of the rest of the brain

‘Releases’ reactions

We don't know much