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Monday, January 6th, 2020
ADMIN STUFF
• Review sessions (time and location TBD)
• Thursday, January 16th - Review of neuroscience techniques
• Thursday, January 23rd - Review of reinforcement learning theory & dopamine signaling
• Thursday, January 30th - Pre-midterm 1 review session
• Thursday, February 20th - Review of hunger circuitry
• Thursday, February 27th - Review of hippocampal physiology and memory
• Thursday, March 12th - Pre-midterm 2 review session
• Thursday, March 26th - Review of basic cell biology
• Thursday, April 2nd - Review of Wayne Sossin’s material
• Thursday, April 9th - Pre-final exam review session
INTRODUCTION
Learning and memory
• Learning occurs through reinforcement
o Reinforcement (also called “reward” in literature): what makes it so that a random
behaviour becomes recurring
o In other words: likelihood of repeating an action depends on whether the action was
reinforced
▪ For example, operant conditioning works in this manner
Molecular composition of cells
• Neurons largely consist of organic molecules made of carbon, hydrogen, nitrogen, oxygen,
phosphorus and sulphur.
• Cell mass breakdown:
o 70% water
o 30% dry weight:
▪ 15% Sugars
▪ 10% Lipids
▪ 15% Nucleic acids
▪ 50% Amino acids
▪ 10% Other organic molecules
Proteins
• Proteins are what do things in cells.
o Enzymes are proteins that perform (catalyze) chemical reactions.
o Receptors are proteins that sense things and react accordingly.
• Proteins also:
o Make up the scaffolding and roads of a cell.
o Mediate transport and storage.
o Act as messengers.
• DNA and RNA (nucleic acids) code for proteins.
DNA and RNA
• Some vocabulary:
o A chromosome is a strand of DNA.
o A gene is a section (a functional unit) of a chromosome → encodes for proteins.
o Transcription is the process of converting DNA to RNA
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,McGill University PSYC 318
o Translation is the process using protein-coding RNA (messenger RNA, mRNA) to
make proteins
▪ Translation occurs in the ribosomes
o The genome of a cell is all the DNA sequences in the soma (cell body).
▪ The genome provides the information necessary to synthesize all the proteins for
a particular organism.
▪ All nucleus-containing diploid cells in a body has the exact same DNA encoding
for the exact same genes. Cell differentiation is due to the change in gene
expression, and not in gene content.
o Protein isoforms are proteins who are coded by the same gene, but the mRNA has
undergone different splicing resulting in variants of the same protein
• Humans have about 20,000 protein-encoding genes in their genome.
o Animals vary from one another based on the genes that they express and the quantity
and location of these expressed genes. The vast majority of proteins throughout living
organisms is made of the same 20 basic amino acids.
• Most DNA is non-coding, meaning it doesn’t contain any genes
o This DNA contains regulatory elements (for example, promoter regions) and “junk” RNA
Molecular interactions
• Molecules interact with each other with varying degrees of affinity.
• Affinity: how well two interacting molecules “stick” to each other
• Molecule-molecule interactions can lead to:
o The formation of complexes (for example, many proteins assemble to produce a catalytic
complex)
o A change in structure of involved elements, which often leads to…
o …A change of function
▪ For example:
• Change of shape of DNA allowing polymerase complexes to bind
• Change of shape leading to the modification of activity of a catalytic
domain of a protein
• Etc.
The basics of neurons
• Structure:
o Cell soma (AKA cell body): main part of the cell,
where the nucleus is located. Most metabolic
functions of the cell are here.
▪ Nucleus: houses the DNA (the
chromosomes).
▪ Neurons are typically classified by the
location of their soma
• For example:
hippocampal neurons
have their soma in the
hippocampus
o Cytoplasm: gelatinous, semi-transparent
fluid in which organelles are suspended.
o Cell membrane: phospholipid bilayer
boundary of the cell. Contains proteins
with specialized functions
o Microtubules allow for rapid transport of
material throughout the neuron.
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,McGill University PSYC 318
o Mitochondria extract energy from nutrients.
▪ This energy is typically stored in the molecular bonds of the molecule ATP.
o Dendrites are branched, treelike extensions of the soma.
▪ Typically receive information from other cells and carry it to the soma.
▪ This information changes the likelihood of the cell to fire an action potential
o Axon terminals are button-like endings of the axon branch. They release
neurotransmitters after receiving an action potential.
Synapses:
• The junction between an axon
terminal and the membrane of
another neuron.
• Different types:
o Axonal-dendritic: axon
terminal synapses on a
dendrite or a dendritic
spine
o Axonal-somatic: axon terminal synapses on the cell soma
o Axo-axonal: axonal terminal synapses on another axonal terminal (this is usually to
modulate how much neurotransmitter is released by the main synapse, since the
amplitude of APs is not changeable.
▪ Purpose:
• Presynaptic inhibition
o Reduce the amount of neurotransmitter released by the second
neuron when it has an action potential.
o Can act through:
▪ Hyperpolarization of the cell membrane
▪ Decrease of the likelihood of the Cav channels opening
▪ Decrease of the amount of time Cav channels stay open
• Presynaptic facilitation
o Increase the amount of neurotransmitter released by the second
neuron when it has an action potential.
o Can act through:
▪ Depolarization of the cell membrane
▪ Increase of the likelihood of the Cav channels opening
▪ Increase of the amount of time Cav channels stay open
• 2 kinds of neurotransmission:
o Fast: mediated by ion channels, ms timescale
▪ Directly changes the membrane potential
o Slow: mediated by metabotropic receptors (which are G-protein-coupled receptors
(GPCRs)), hundreds of ms timescale and long-lasting changes
▪ Induce a signalling cascade which modifies gene expression.
• Receptors for neurotransmitters can also be located:
o On the cell that released the neurotransmitter (auto-receptor, usually useful for feedback)
o On the post-synaptic cell (post-synaptic receptor)
The activation of receptors leads to communications between neurons
• Post-synaptic potentials (PSPs): alterations in the membrane potential of a postsynaptic neuron
o Produced by neurotransmitter release into the synapse and receptor activation.
o Can be:
▪ Excitatory (EPSP):
• Influx of cations (e.g. Na+, Ca2+)
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, McGill University PSYC 318
• Efflux of anions (e.g. Cl-, early in development)
▪ Inhibitory (IPSP)
• Efflux of cations (e.g. K+)
• Influx of anions (e.g. Cl-)
• The nature of the receptor determines whether a signal is excitatory or inhibitory
o Ionotropic receptors (e.g. GluRs, GABARs) have varying affinity for different ions, and
this determines which ions pass through the channel pore
o Metabotropic receptors modulate the activity of ionotropic receptors through a variety of
mechanisms→effect of metabotropic receptor depends on the G-protein it is coupled with
▪ This is the reason why serotonin, dopamine, norepinephrine, etc. can have
inhibitor or excitatory effects based on the receptors they act upon.
▪ They can open G-protein-gatedd channels, which can either pass anions or
cations
Neural integration:
• If only a couple EPSPs occur at one time, the influx of sodium ions
will likely not cause an action potential.
o The depolarizing effect of the incoming sodium ions will be
counteracted by an increase in the outflow of potassium ions
through leak channels.
• → if Na+ enters the cell, the probability of K+ leaving increases→ we
need summation of input to trigger an action potential.
o This depolarization must reach the beginning of the axon
hillock where voltage-gated sodium channels are
congregated to trigger an action potential.
▪ Note: THIS IS ACTUALLY INCORRECT. Recent
data shows that the axon hillock doesn’t contain Nav channels and is actually just
the junction between the soma and the axon. The action potential originates in
the axon initial segment.
G-protein signalling
• G-protein signaling cascades can affect multiple downstream processes, including:
o Opening G-protein-gated ion channels
o Changes in gene transcription
o Secretion of substances from the cell
o Etc.
• There are more different kinds of g-protein linked receptors than there is of any other class of
protein encoded in our genome.
o Respond to a myriad of stimuli: neurotransmitters, neuropeptides, sensory inputs (e.g.
light), etc.
• Downstream effect is determined by the specific sub-type of the G-protein and the local effectors
activated by it.
o For example: β-norepinephrine (β–noradrenergic) receptors are coupled to Gs →
adenylate cyclase activation
o α-norepinephrine (α-noradrenergic) receptors activate Gi →inhibits adenylate cyclase
protein.
Neurotransmitters
• Cells are sensitive to signaling molecules, which represent information.
• Most signaling molecules fit into two broad categories:
o Amino acids (including proteins and amino acid derivatives)
o Lipids (including fats and cholesterol derivatives such as steroids)
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