Midterm #1 Flashcards
What is consciousness
The state or quality of awareness (awareness of thoughts, perceptions, memories, and feelings). The state of awareness creates a subjective experience. Anything capable of having a subjective experience is conscious.
The split-brain operation
Outdated surgical approach for treating seizure disorder (epilepsy). Involves cutting the corpus callosum. The hemispheres can’t communicate directly with one another. Coordinated movement is still possible thanks to the brainstem and spinal cord.
Corpus callosum
The bundle of white matter tracts connecting the left and right hemispheres.
Cerebral Hemispheres
Consciously process sensory information (sights, sounds, touch), and initiate purposeful movement (hand and leg movements). Some lateralized function (controlled primarily by a single hemisphere), but the nerve fibres mostly crisscross.
Left brain functions
Control of muscles on right half of the body. Complex language comprehensions, speech, writing. Processing right half of visual field.
Right brain functions
Control of muscles on left half of the body. Limited language, small ‘dictionary’. Processing left half of visual field.
Left and right visual fields and fixation points
When focusing on a fixation point, vision is divided into a left and right visual field. The left visual field is processed by the right half of each eye, and the right visual field is processed by the left half of each eye.
Nasal half of visual information and brain hemispheres
Nasal half of visual information (the half closer to the midline) crosses over at the optic chasm. Left hemisphere of brain processes right visual field. Right hemisphere processes left visual field.
Cutting The Corpus Callosum
The corpus callosum enables the two hemispheres to share information so that each side known what the other side is perceiving and doing. If it is cut, the two hemispheres cannot directly talk to each other. However, they can still send information towards (to the brainstem and spinal cord) to control muscles.
The role of lower brain areas after receiving info from corpus callosum
They process information beneath conscious awareness, and they help coordinate movements by integrating the information they receive from the two cerebral hemispheres.
Dilemma of the split brain patients
Some patients began to say that their left hand had a mind of its own. It seemed that the left hand of split-brain patients was controlled by processes outside their conscious awareness. The right hand, controlled by the left brain, never acted out of the ordinary. Its actions were always consistent with the person’s conscious intentions.
Studies on Split Brain Patients: Touch
When a split-brain patient closes their eyes and touches a familiar but unidentified object with their left hand, they cannot identify the object out loud.
Studies on Split Brain Patients: Vision
When a split-brain patient sees an image only in their left peripheral vision, which is processed on the right side of the brain, they cannot verbalize what they see. Split brain patients cannot say out loud something that only the right brain sees.
Gazzaniga’s Interpreter Theory
In experiments with split brain patients, researchers give a visual command to the nonverbal right brain. Then ask the patients to verbally explain why they had done that thing. The left brain would create a story to explain the behaviour. Gazzaniga theorized that this is how unified conscious experience arises. Our behaviour is out of our control. the left brain develops a meaningful narrative through which we can understand our experiences.
Mind-Body Dualism
While the body may be a mechanical device and the world deterministic, the mind (or soul) is something else, something immaterial that exists outside the body.
Cartesian impasse
If the movement of all atoms can be well explained by the physical laws of nature, how can our immaterial souls control our material bodies?
What are atoms
Atoms are made of protons, neutrons, and electrons. Every element is a type of atom. Atoms can bond to form molecules. In an atom or molecule has a charge, it is an ion.
What are molecules?
Atoms interact with each other when it improves their ability to balance out or distribute their electrical charge. The sharing of electrons: covalent bon. A molecule is two or more atoms connected with covalent bonds. Covalent bonds do not break apart in water.
What are salts?
Atoms interact with each other when it improves their ability to balance out or distribute their electrical charges. When an atom or molecule has a net electrical charge (+ or -) we call it an ion. Negatively charged ions can donate an electron to positively charged ions, creating an ionic bond.Atoms and molecules connected with ionic bonds are Calle salts. Salts dissolve in water because ionic bonds break apart in water.
CHNOPS
Carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulphur. These atoms represent the six key chemical elements whose covalent combinations make up most of the biological molecules on Earth.
The CHNOPS form 5 main molecules
Water, Sugar, Fat (lipids), Nucleic acids, Amino acids.
RNA
Single stranded chain of nucleic acids. Fragile. Strands of RNA can naturally fold into complex 3-dimensional shapes, and some of them can catalyze chemical reactions.
Ribozymes
Subgroup of RNA that can catalyze chemical reactions. Thought to give rise to first life on Earth.
Two main problems with ribozymes (molecules of RNA)
1) RNA is fragile. Breaks apart easily.
2) RNA is made of 4 different types of nucleotides that are not particularly abundant on planet Earth.
DNA
Double stranded chain of nucleic acids. Stable. In eukaryotes, stored safely in the nucleus. Primary storage of genetic info today.
To make a quality cell, you need a quality membrane.
Hydrophilic (water loving) phosphate head. Hydrophobic (water hating) lipid tail. The structure makes diffusion (movement) across the membrane difficult - a good thing if you want an enclosed cell.
Prokaryotic cells
Single cell organisms. Cell membrane filled with cytoplasm. DNA, RNA, and ribosomes floating around.
Eukaryotic Cells
Single - or multi-celled organisms. Contains organelles like mitochondria and nucleus. Can now store DNA and create energy.
Proteins
Proteins are what do things in a cell. Proteins are chains of amino acids. They are considered macromolecules (big).
Protein Synthesis
- A segment of DNA in the nucleus is unraveled and a complementary strand of RNA is created (mRNA).
- mRNA leaves the nucleus.
- Ribosome latches onto mRNA, recruits tRNA to creatre complementary amino acids.
- Amino acids are added to a growing chain that eventually breaks off and folds into a protein.
Ribosome
A molecular machine that is made of RNA and proteins. Ribosomes have perfected the synthethis of new proteins by stringing together the amino acids held by tRNA molecules in the order determined by free-flowing strands of mRNA.
Why is DNA so important
Because RNa is not stable it breaks apart too easily to be useful for long term information storage. DNA is much more stable and durable than RNA. DNA and RNA are complementary, so it is easy to transcribe one into the other. For long term info storage, cells evolved to use DNA instead of RNA.
Phospholipids and the cell membrane
Phospholipids are strands of fat (lipids) with a phosphate cup. Lipids prefer the company of other lipids. Phosphate caps prefer to interact with water. Phospholipids form bilayer sheets if left understated (in water), and form micelles when shaken (soap bubbles). Under the right conditions, micelles can pop and reform as liposomes. The cell membrane is basically a liposome. Diffusion through the phospholipid bilayer is limited. Inside and outside are salt water.
The Eukaryotic Cell Body (SOMA)
The cell body (or soma) of a cell is where its nucleus is located. Filled with cytoplasm, mitochondria, membrane, microtubules.
Cytoplasm
Water filled with salt, sugar, nucleic acids, and amino acids
Mitochondria
Semi-autonomous double membrane-bound organelles. Powerhouse of the cell because they generate ATP, the cell’s main source of chemical energy.
Cell membrane
Defines the boundary of the cell. It consists of a phospholipid bilayer that is embedded with proteins.
Microtubules
Allow for rapid transport of material within the neuron.
Multicellular organisms
Consist of more than one cell. In multicellular organisms, cells specialize to perform distinct functions. All cells within these organisms have the same genome (same collection of DNA), but they read different parts of it.
Crystallization
Process of atoms or molecules arranging into a well-defined, rigid crystal lattice in order to minimize their energetic state. Water molecules crystallize when they freeze, and the unique way they arrange themselves causes ice to be larger than water.
What is a neuron
Specialized type of cell that is electrically excitable. Neurons send electrical and chemical signals that permit fast communication.
Reticular Theory of a neuron - Golgi
Believed that the brain was a physically connected network
Neuron Doctrine theory of a neuron - Cajal
Believed that the brain was composed of individual cells communicating.
Neuron Anatomy
- Soma (cell body): Location of the nucleus and other organelles.
- Dendrites: sites for receiving chemical or sensory input
- Axon: Electrical signals (action potentials) are sent down the axon. Only one axon, but that axon can branch many times.
- Axon terminals: End of axon, where the action potential triggers the release of neurotransmitter.
Phospholipid bilayer of a neuron
Cell membrane. Ions cannot move across it. Filled with Cytosol: salty water-like solution. Filled with potassium, chloride, and sodium.
Voltage of a Neuron
Difference in electric charge between two points - the electrostatic potential between two points. When there is some voltage, it makes charged particles want to move to neutralize the charge difference. Cell membranes prevent this from happening. Measurements of voltage are always relative: the extracellular fluid of the brain is always considered to have a charge of 0mV.
Resting membrane potential of neurons
Relative to the extracellular fluid (mV), neurons have a resting membrane potential of -40mV to -90mV. This means that the voltage across the membrane makes positively charged ions want to enter the cell and negatively charged ions want to leave the cell.
How do neurons communicate? (Electrically vs. chemically)
Electrically: Relies on membrane potential (Vm = difference in charge between inside and outside of cell). Within a cell.
Chemically: Relies on neurotransmitter release from axon terminal onto other neurons. Between cells.
Ions
An atom or molecule that has a net electrical charge. Move around freely in water.
Cations: positively charged. (Na+, K+ (more abundant inside cell), Ca2+, Mg+)
Anions: negatively charged. (Cl-)
Why do neurons have an especially negative membrane potential?
To be able to communicate very quickly from on end of the cell to the other. They need a way to pass info down the length of axons very quickly.
How do neurons create an electrical potential across their membrane
Using two proteins: 1.
Sodium potassium pump
2. Potassium leak channel.
Two other proteins used in an action potential
- Voltage gated sodium channel
- Voltage gated potassium channel
Protein that action potentials trigger the release of
Voltage-gated calcium channel
The Sodium-Potassium Pump
Sets the concentration gradient; sends Na+ out of cell, and K+ into cell. Makes the concentration of K= ions 30x higher inside the cell than out. Makes the concentration of Na+ ions 15x more concentrated outside the cell than in. These concentration gradients never change.
The Force of Diffusion
If there is a concentration gradient and no forces or barriers in the way, then atoms and molecules will move, on average, from regions of high concentration to regions of low concentration.
Potassium Leak Channels
Permanently open ion channels that freely let K+ ions enter or leave the cell. Since K+ ions are 30x more concentrated inside the cell than out, they are more likely to leave the cell (diffusion). The force of diffusion competes with the force of electrostatic pressure. K+ ions leave the cell because of diffusion, but enter the cell because it is negatively charged inside relative to outside. These forces become equal and opposite when the membrane potential falls to -90mV.
The balance of diffusion and electrostatic energy
When a neuron’s membrane potential equals -90mV, there is no net movement of K+ ions: the amount leaving = the amount entering. When it is less negative than -90mV, diffusion outcompetes electrostatic pressure and more K+ ions leave the cell. When it is more negative than -90mV, electrostatic pressure wins and more K+ enters the cell than leaves.
The Resting Membrane Potential
The resting membrane potential of most neurons is typically between -40 and -80 mV, because other ions (primarily Na+) continuously flow into neurons through other types of ion channels and pumps. But it is the permeability of the membrane to K+ ions that largely determines the resting membrane potential. When a neuron opens up more K+ channels, the membrane potential falls closer to -90mV, when a neuron removes some K+ channels from the membrane, the membrane potential becomes less negative.
Ion Channel Receptors
The dendrites of most neurons are full of receptors that are ion channels. When activated, these receptors change shape and open a pore through which ions can flow, in or out. When these receptors get activated, the gate briefly opens, allowing specific ions to flow through the pore of the ion channel receptor.
Membrane depolarization
When the membrane potential of a cell becomes less negative than it normally is at rest. Thea activation of a receptor that allows positively charged Na+ ions to enter the cell will depolarize the membrane.
Changes in the membrane potential
Changes are always transient (short lived). Neurons are quick to return to their state because K+ leak channels are always open. The abundance of K+ leak channels ensures that neurons never deviate from their resting membrane potential for very long.
The Voltage-Gated Sodium Channel
At rest, the electrically charged gate is pulled closed by the negatively charged interior of the cell. But if Na+ comes in through an activated receptor, depolarizing the membrane, this gate may not stay closed. Thegate opens when the membrane is depolarized to about -40mV. The open pore allows NA+ ions to rush into the cell, further depolarizing the membrane. A receptor started the depolarization. Voltage-gated Na+ channels continue it. The gate opens for no more than half a millisecond before the pore becomes clogged by a ball on a chain. This ball will clog the pore until the membrane potential gets back down to -70mV (takes another half millisecond).
The action potential
A brief electrical impulse that propagates down the axon. A rapid change in the membrane potential that travels down the entire length of the axon due to the opening of voltage-gated sodium channels.
Threshold of excitation
The value the membrane potential must reach to trigger an action potential is called the threshold of excitation.
What starts an action potential?
We now have a negatively charged cell - positive ions want to come in because of electrostatic pressure. Sodium also wants to come in to move down the concentration gradient. There will be a depolarization stimulus: receptor binding opens ion channels, allowing initial influx of Na+.
Voltage-gated Potassium Channel
Opens during the upswing of the action potential (~0mv); responsible for return to baseline Vm. When they open, the cell membrane is more permeable than ever to K ions. The outward flow of K+ ions through both leak channels and voltage-gated potassium channels stores the resting potential.
Refractory period
When the resting membrane potential is restored, all voltage-gated ion channels close and reset. However, by the time all the voltage-gated potassium channels close, the membrane potential will have fallen below what it normally is at rest. This post action potential hyper polarization is called the refractory period. It is hard to trigger another action period when the membrane is this hyper polarized.
Voltage-gated calcium channels
When the action potential reaches the end of the axon (axon terminal), it triggers the opening voltage-gated calcium channels. Calcium is 1000x more concentrated outside the cell than in, so it rushes into the cell. The influx of calcium triggers the fusion of neurotransmitter-filled vesicles. Neurotransmitters are released into the synapse, where they activate receptors on a downstream cell.
Synaptic transmission
The primary means of communication between neurons. Transmission of chemical messages (neurotransmitters) from one neuron to another via synaptic connections. Released neurotransmitters activate proteins on downstream neurons, which can allow Na+ ions to enter those cells.
Why doesn’t the action potential travel backwards?
An action potential involves an influx of positive charge into the cell. The influx of positive ions pushes other positive ions away (down concentration gradient). Previously active voltage-gated Na+ channels are in refractory period (ball is clogging the pore) - influx of positive ions cannot reopen them.
The all-or-none law
An action potential can occur or not, but once triggered it propagates down the length of the axon without growing or diminishing in size. No such thing as a strong or weak action potential.
Rate law
The strength of the “message” is represented by the rate of firing (the number of action potentials per second, rather than the size or speed of the action potential).
Myelination
Propagating the action potential can be slow and axons can be long. Myelination makes this more efficient by wrapping an insulating layer of fat around segments of the axon.
Hydrated ions (K+ vs Na+)
When dissolved in water, ions get surrounded by water molecules - they come hydrated. K+ ions are equally happy when inside the pore of a potassium ion channel or when surrounded by water. Na+ ions are too small to comfortably fit (unhydrated) in the pore of a potassium ion channel, so they prefer to stay outside of those ion channels with their hydration shell intact.
Two types of cells in the central nervous system (CNS):
- Neurons: responsible for the electrical signals (action potentials) that communicate information about sensations and movements.
- Glial cells: serve a variety of support functions for neurons
4 types of glial cells
- Astrocytes
- Microglia
- Oligodendrocytes
- Ependymal cells
Astrocytes
Janitors of the cell, break down and clean up waste, provides scaffolding for other cellular functions.
Microglia
Provide immune support, regulate cell development and respond to injury.
Oligodendrocytes
Create myelin, wrap it around nearby axons, can provide sheath for 50 axons, Schwann cells = equivalent in peripheral nervous system.
Ependymal cells
Line the ventricles, circulate cerebrospinal fluid (CF)
Nodes of Ranvier
Each segment of myelin is separated by 1 micron of exposed axon. The exposed segments of myelinated axons are called the nodes of Ranvier. They are the only places where myelinated axons feel a charge difference between inside and out.
Synapse
A junction between the axon terminal (terminal button) of the sending neuron and the cell membrane of the receiving neuron. Communication across the synapse is mediated by the release of a signalling molecule from the axon terminal.
Synaptic vessicles
Contain molecules of neurotransmitter. They dock at presynaptic membrane and release neurotransmitter into the synaptic clef.
Synaptic cleft
The space between the pre- and postsynaptic membrane.
Presynaptic membrane
The axon terminal of the sending neuron. It is where neurotransmitter is released from.
Postsynaptic membrane
The membrane of the receiving cell that is opposite the axon terminal. Neurotransmitters released from presynaptic membrane flow across the synapse to postsynaptic membrane, where they bind and activate receptors.
Ligand
A signalling molecule that binds to a receptor. Signaling within and between cells occurs through ligand-receptor interactions.
Ionotropic recetor
Ion channels. Direct, fast effect on cell potential.
Metabotropic receptors
Are not ion channels; mostly mediate their effects through g-protein signalling cascades, can act indirectly on ion channels, slower modification of cell excitability
Intracellular receptors
Receptors that are located inside the cell
Surface receptors
Located on the cell membrane. Are further specified as being: 1. Postsynaptic receptors: located on postsynaptic membrane.
2. Presynaptic receptors: located on presynaptic membrane.
3. Extrasynaptic receptors: located near but outside a synapse.
Diffusion
Passive movement from areas of high concentration to areas of low concentration
Enzymatic deactivation
Destruction of a neurotransmitter by an enzyme. For example. acetylcholine is broken down in the synaptic cleft by the enzyme acetylcholinesterase.
Reuptake
Reuptake transporters recycle neurotransmitters by pulling them back into the cell that just released them.
Postsynpatic potential
When a neurotransmitter binds to a postsynaptic receptor and changes the membrane potential of the postsynaptic cell. Ionotropic receptors produce rapid postsynaptic potentials, metabotropic receptors do not always produce postsynaptic potentials but when they do, they are relatively slow/delayed. Beyond being slow or fast, postsynaptic potentials are also excitatory or inhibitory.
Excitatory postsynaptic potentials (EPSPs)
These are the result of positive sodium ions entering the postsynaptic cell, causing membrane depolarization and perhaps an action potential.
Inhibitory postsynaptic potentials (IPSPs)
These are often the result of negative chloride ions entering the cell, causing membrane hyperpolarization and fewer action potentials.
Depolarization
When the membrane potential of a cell becomes less negative than it normally is a rest. The opening of Na+ ion channels will depolarize a neuron, making it more likely to spike.
Hypoerpolarization
When the membrane potential of a cell becomes more negative than it normally is at rest. The opening of Cl- ion channels can hyper polarize a neuron, making it less likely to spike.
Action Potential Generation and EPSPs
Activity of excitatory synapses produces EPSPs in postsynaptic neuron. Axon hillock reaches threshold of excitation; action potential is triggered in axon. An EPSP does NOT always induce an action potential in the postsynaptic neuron.
Neural integration and IPSPs
Activity of inhibitory synapses produces IPSPs in postsynaptic neuron. IPSPs counteract EPSPs; action potential is not triggered in axon. This is called neural integration. When EPSPs and IPSPs occur at the same time, the influx of negatively charged chloride ions diminish the impact of the positively charged sodium ions.
Excitation vs Inhibition
It is the receptor that is expressed by the postsynaptic cell that determines whether a neurotransmitter will be excitatory or inhibitory, not the neurotransmitter itself.
Metabotropic Receptors
These receptors typically have a single protein that spans the membrane and is linked to intracellular signaling pathways via G proteins. When a ligand binds, it activates G proteins, which then initiate a cascade of intracellular events. The response is slower, occurring over seconds to minutes.
Neural excitation versus behavioural excitation
The firing of excitatory neurons deep in the brain does not necessarily cause movement, and the firing of inhibitory neurons does not necessarily inhibit movement.
Receptor protein
A protein that is sensitive to a stimulus and passes along the message. It can be a neurotransmitter receptor or a receptor for something else. All receptors are either ionotropic or metabotropic.
Ionotropic Receptor
A receptor that is an ion channel. Direct, fast effect on cell’s membrane potential through ion influx. Ligand binding opens ion channel. Cases an EPSP (depolarization and more spiking) or causes an IPSP (hyperpolarization) and less spiking), depending on whether the pore of the ion channel is permeable to Na+ or Cl-.
G-Protein Coupled Receptors
Proteins that use GTP as an energy source for chemical reactions. Ligand binding to receptor drives a sequence of events by which the G protein can catalyze chemical reactions around the cell.
G-Protein Coupled Receptors Steps
- Neurotransmitter binds and the receptor changes shape, forcing the G protein to let go of GDP from a previous activation.
- A nearby GTP molecule can bind to the newly opened site on the G protein.
- The G protein and its bound GTP will dissociate from the receptor and catalyze chemical reactions.
- The G protein will eventually convert GTP to GDP, at which point it will reassociate with the receptor.
Opening of G-Protein-gated ion channels
1) a signalling molecule has to activate a metabotropic receptor
2) allowing a g-protein to become activated
3) the activated G protein can bind (directly or indirectly) to a g-protein-gated ion channel
Synapses can form between an axon terminal and…
1) smooth dendrite (a dendritic shaft)
2) a dendritic spine
3)a soma (cell body): these synapses exert great control over whether the cell fires, due to proximity to axon hillock
* first three locations are well-positioned to generate an action potential
4) another axon terminal (axoaxonic synapse)
Axoaxonic Synapses
Axoaxonic synapses regulate the amount of neurotransmitter that the second neuron will release when it has an action potential. Presynaptic inhibition vs presynaptic facilitation.
Presynaptic inhibition
Axoaxonic synapses can hyper polarize the axon terminal of the downstream neuron, so its voltage-gated calcium channels will not open as much as they normally do when there is an action potential. The net effect is to reduce neurotransmitter release from the red cell when it has an action potential.
Presynaptic facilitation
Axoaxonic synapses can depolarize the axon terminal of the downstream neuron, so that its voltage-gated calcium channels are more likely to open when an action potential arrives. The net effect is to increase neurotransmitter release from the red cell when it has an action potential.
Autoreceptor
A receptor located on presynaptic membrane that makes the cell sensitive to its own neurotransmitter release. They are gated by the release of neurotransmitter from the cell they are in. Autoreceptors are always metabotropic and inhibitory. Main source of presynaptic inhibition.
Postsynaptic receptor
Receptor located on the receiving neuron (not on the cell that is releasing the neurotransmitter).
Neurotransmitters
Signaling molecules released in the brain to regulate neural activity.
Four main categories of neurotransmitters
- Classical, conventional neurotransmitters: glutamate, GABA, dopamine, serotonin, norepinephrine, acetylcholine
- Neuropeptides: more than 70 different types
- Lipid-based neurotransmitters: primarily the endocannabinoids
- Gasotransmitters: primarily nitric oxide.
Glutamate
Main excitatory neurotransmitter - because all inotropic glutamate receptors let sodium in. Drugs that activate glutamate receptors often cause seizures and excitotoxicity. Drugs that block glutamate receptors slow you down.
GABA
Main inhibitory neurotransmitter - because all ionotropic GABA receptors let chloride in. Drugs that block GABA receptors often cause seizures. Drugs that activate GABA receptors slow you down (sleeping pills, muscle relaxants, alcohol..etc)
Dopamine, Norepinephrine, Acetylcholine, Serotonin
Main neuromodulators - These neurotransmitters primarily act on metabotropic receptors and tend to exert a modulatory influence on cell activity (in contrast to glutamate and GABA, which often cause fast EPSPs or IPSPs via their respective inotropic receptors).
Classical Neurotransmitters
Modified amino acids (small molecules). Synthesized locally in axon terminals. Secreted from small synaptic vesicles. Activates Ionotropic AND metabotropic receptors. Recaptured and reused visa reuptake proteins.
Neuropeptides
A small chain of amino acids. Synthesized in the cell body, then transported down the axon and released just once. Secreted from large dense core vesicles. Activates metabotropic receptors. Not recycled - no reuptake.
Lipid-based signalling molecules
Fat soluble molecules. Synthesized and released on demand as needed. Secreted usually from postsynaptic cell, does not require vesicles. Activates metabotropic receptors. No reuptake.
When classifying a neurotransmitter, we ask…
1) What type of molecule is it?
2) How and where is it made?
3) How does it get released?
4) What kind of receptors can it bind to?
5) How does it get cleared away after it is released?
The life of a Neurotransmitter
- Synthesized from a precursor molecule (an amino acid) by enzymes in the axon terminal.
- Neurotransmitter is packaged into vesicles by transporter proteins.
- Vesicles are released into the synapse through fusion to the membrane (exocytosis)
- Some neurotransmitter binds to postsynaptic receptors, some binds to auto receptors to downregulate release.
- Neurotransmitter in the synapse is cleared away by reuptake proteins (return neurotransmitter to cell it was released form) and enzymes (degrade neurotransmitter).
The Monoamine Neuromodulators
Serotonin, dopamine, and norepinephrine have a similar chemical and 3D structure called monoamines. They are released by different neurons, and they activate different receptors, but only protein packages them into synaptic vesicles: the vesicular monoamine transporter (VMAT).
Drugs
Exogenous chemicals that alter cell function at low doses. Direct: affect activity by binding to postsynaptic receptor. Indirect: affect activity by interacting with something other than the postsynaptic receptor.
Direct Drugs: Competitive
Affect activity by binding to postsynaptic receptor at the same site as endogenous neurotransmitter. Agonist: Full, Partial. Antagonist: Full
Direct Drugs: Noncompetitive
Affect activity by binding to postsynaptic receptor at a different site than endogenous neurotransmitter. Agonist: Full, Partial, Positive Allosteric Modulator. Antagonist: Full, Negative Allosteric Modulator.
Partial Agonists
Can cause a net increase or decrease in postsynaptic activity. Depends on baseline activity at the synapse. If there is no receptor binding, the receptor activation is 0%. At a highly active synapse, neurotransmitter is frequently binding to receptors. Neurotransmitter binding causes maximal activation of receptor - at baseline, receptors are activated 100%. The drug has higher affinity, so binds to receptors instead of neurotransmitter. BUT it doesn’t activate them as strongly - receptors are activate 50%. Although the drug activates receptors, the net effect on activity is a decrease.
Positive Allosteric Modulators
A positive allosteric modulator amplifies the effect of neurotransmitter binding. Alcohol and benzodiazepines are both examples of positive allosteric modulators for GABA. A negative allosteric modulator decreases the effect of neurotransmitter binding.
Acetylcholine
Acts as a neuromodulator in the CNS (brain & spinal cord), often at axoaxonic synapses. It is also the primary neurotransmitter released by motor neurons at the neuromuscular junction. There, it activates excitatory inotropic receptors on muscle cells, causing fast EPSPs and muscle contraction.
The Black Widow Spider
One of the toxins in her venom causes a massive release of acetylcholine in the neuromuscular junction, which causes muscle cramps, pain, and nausea.
Botulinum toxin (botox)
Produced by bacteria that grow in improperly canned food. It prevents acetylcholine release from motor neurons, causing muscle paralysis.
Antipsychotics (neuroleptics)
Class of drugs used to treat psychosis. They are mostly dirty drugs, which means they bind to more than one type of receptor. However, the action they all have in common is they directly block the dopamine D2 receptor, which is an inhibitory metabotropic receptor expressed by neurons all over the brain.
Biased Agonism
When a ligand causes a metabotropic receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different G protein.
Methylphenidate, Cocaine
Drugs that block catecholamine reuptake transporters, meaning they block the reuptake of dopamine & norepinhephrine.
Adderall, Crystal meth
Drugs that reverse catecholamine reuptake transporters, causing dopamine and norepinephrine to flow out of the axon terminal before being packaged into a vesicle.
Repeat Administration on Tolerance
Drug effects are lessened due to the body down regulating natural processes that do the same thing. E.g., if dopamine levels are elevated because of regular cocaine use, the body will synthesize less dopamine to bring levels closer to normal.
Repeat Administration on Withdrawal
Cessation after regular use causes the inverse of symptoms. E.g, stimulate withdrawal causing fatigue, opiate withdrawal causing dysphoria.
Parkinson’s disease
A neurological disorder that is characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements. Caused by the degeneration (death) of dopamine neurons in the midbrain.
Amino acid L-Dopa
Used as a drug to treat Parkinson’s disease because it increases dopamine production in the brain and acts as an indirect dopamine receptor agonist.
Similarities & differences between Heroin, Morphine, & Imodium Anti-Diarrheal
Heroin: Very easily crosses the blood-brain barrier (because an enzyme in the blood makes it very lipid/fat soluble).
Morphine: Less easily crosses the blood-brain barrier (it is less lipid soluble than heroin)
Imodium.
Anti-Diarrheal: Does not cross the blood-brain barrier.
All very strong opiates that cause constipation.
Neurogenesis
A production of new neurons. Neural progenitor cells produce neurons and glia after they undergo asymmetrical cell division.
Apoptosis
A process of programmed cell death that occurs in multicellular organisms. Highly regulated and controlled form of cell suicide that ensures a dying cell does not cause problems for its neighbours.
Central Nervous System (CNS)
Everything in the brain AND spinal cord.
Peripheral nervous system (PNS)
Any part of the nervous system outside the brain and spinal cord.
Distinction between CNS and PNS
In the CNS, myelin is created by Oligodendrocytes. In the PNS, myelin is created by Schwann cells.
Extracellular fluid in the body & brain
There are small holes in the blood vessels that course around your body. The liquid part of blood (blood plasma) continually leaks out of these holes. This liquid forms the extracellular fluid of your body. Extracellular fluid flows around cells providing nutrients and collecting waste. Blood –> Extracellular fluid –> Lymph –> Blood
Blood Brain Barrier
The CNS does not participate in the lymphatic system of the body because there are no holes in the blood vessels that pass through the brain and spinal cord. This property is known as the blood brain barrier.
Cerebrospinal fluid
Rather than letting blood plasma directly leak out of the circulatory system, the brain makes its own extracellular solution by actively picking out exactly what it needs from the blood.. This liquid it makes is called cerebrospinal fluid (CSF).
Projection neurons & interneurons in CNS
Projection neuron: has an axon that innervates distal areas of the brain; it synapses on neurons that are far away from where the axon started.
An interneuron: only synapses on local, nearby neurons. Its axon doesn’t go far.
The axons of motor neurons in PNS
Part of the PNS. These axons are Efferent fibres (outputs), bringing information away from the CNS. Motor neurons control muscle contraction and gland secretion.
Sensory neuron dendrites and cell bodies in PNS
The axons of sensory neurons are Afferent fibres (inputs), bringing information towards the CNS. Sensory neurons detect changes in the external an internal environment.
Two types of nerves
1.Spinal nerves: The axons of the spinal nerves enter/leave the spinal cord.
2. Cranial nerves: Enter/leave the brain directly. All cranial nerves (except for one) process movements and sensory information around the head and neck. The vagus: the exception, branches extensively in the upper half of the body.
The Spinal Cord
Principal function is to bring sensory information to the brain and to bring motor fibres to effector organs throughout the body (glands and muscles). It has a certain degree of autonomy from the brain, as various reflexive control circuits are located there.
Somatic vs Autonomic parts of the PNS
Somatic: Interacts with external environment. Afferent nerves carry esnroy signals from the body’s surface TO the CNS. Efferent nerves carry motor signals FROM the CNS to skeletal muscles.
Autonomic: Regulates body’s internal environment. Afferent nerves carry sensory signals form internal organs TO the CNS. Efferent nerves carry motor signals FROM the CNS to internal organs.
Anatomical Directions
Anterior: in front
Posterior: behind
Superior: above
Inferior: below
Rostral: towards the beak
Caudal: towards the tail
Dorsal: towards the back
Ventral: towards the belly
These 4 terms rotate when we refer to human spinal cord.
Lateral: away from the midline
Medial: toward the midline
Neuraxis
Imaginary line that runs along the length of the CNS
2 parts of the Efferent Autonomic Nervous System
Sympathetic division: Primes the body for action, particularly in life threatening situations (fight-or-flight). Is always active to some extent - regulates heart rate, blood flow, and activity of nearly every organ.
Parasympathetic division: Supports activities that occur when the body is in a relaxed state (rest-and-digest). It is always active to some extent - regulates urination, defecation, salvation, and sexual arousal.
Brain nuclei
In th brain, the word nuclei refers to a collection of neurons that are clustered together that regulate a shared function.
Contralateral
Structures on the opposite side of the body. E.g., the motor cortex controls movements of the contralateral hand.
Ipsilateral
Structures on the same side of the body (e.g, taste is processed ipsilaterally). Taste and smell are the only sensory systems that do not have contralateral organization.
The hindbrain
Is the most caudal division of the brain. It includes:
1. Medulla oblongata
2. The pons
3. The cerebellum
Medulla Oblongota
Contains a collection of brain nuclei that regulate autonomic functions (heart rate, blood flow, breathing, vomiting, sneezing). One nucleus is area postrema: initiates vomiting when poisons are detected. Also contains part of the reticular formation: regulates sleep and arousal.
Pons
Bulge in the brain stem that relays info between cerebrum and cerebellum.
The Cerebellum
Cerebellar damage often results in jerky, exaggerated, poorly coordinated movements. Critical for picking up a cup and drinking without spilling. Also plays an important role in motor learning. Afferent fibres to the cerebellum synapse in the superficial cerebellar cortex. Neurons in the cerebellar cortex send axons inwards to the deep cerebellar nuclei. From there, neurons project to the brain and spinal cord.
The Midbrain: Tectum and Tegmentum
The midbrain is a collection of nuclei that orchestrate complex reflexive behaviours.
1. The tectum: (“roof”) appear as two pairs of bumps on the dorsal surface of the midbrain. Top 2 bumps are the superior colliculi - involved in orienting the animal to things in peripheral vision. Bottom 2 bumps are the interior colliculi - involved in orienting to unexpected sounds.
2. The tegmentum includes several structures that coordinate and motivate complex species-typical movements.
The Forebrain: Hypothalamus
Hypothalamus is a bilateral structure made up of several nuclei, which generally regulate autonomic nervous system activity. Involved in behaviours that directly relate to survival. Links the nervous system to the endocrine system (release of hormones into the blood stream) via the pituitary gland. Has similar functions to the medulla.
The Forebrain: thalamus
Relay station. Directing incoming info to different regions of cerebral cortex.
The Forebrain: cerebral cortex
The surface of the brain. Where sensory information enters conscious awareness. It is a multi-layered structure, and neurons are interconnected between layers to form to cortical columns. Input from thalamus and other areas go into layer 4, and outputs from layers 5&6 go to thalamus and other layers of cortex. Outermost portion is gray matter, beneath the grey matter is white matter. Cerebral cortex contains sulci (small grooves), fissures (large or major grooves), gyri (ridges between sulk or fissures).
4 lobes of the cerebral cortex
1.The frontal lobe controls movement
2. The parietal lobe processes touch information
3. The occipital lobe processes visual information
4. The temporal lobe processes auditory information
Sensory Association Cortex
Adjacent to each primary sensory area is Sensory Association Cortex, where perception takes place and memories are stored. Areas of sensory association cortex nearest to the primary sensory areas receive information from only one sensory system.
Longitudinal fissure
Separates the two hemisphere
The lateral fissure
Separates the frontal lobe and the temporal lobe.
The central sulcus
Separates the frontal lobe and the parietal lobe.
Corpus callosum
Although two cerebral hemisphere perform somehwat different functions, perceptions and memories are unified. This unity is accomplished by the corpus callosum, a large bundle of axons that connects corresponding parts of the left and right hemispheres.
The Primary Cortical Areas
Primary motor cortex (frontal lobe): contains motor neurons that synapse in the spinal cord. Different regions control different parts of the body.
Somatosensory cortex (parietal lobe): where touch info enters cerebral cortex. Different regions receive info from different parts of the body.
Primary auditory cortex (temporal lobe): where auditory info enters cerebral cortex.
Primary visual cortex (occipital lobe): where visual info enters the cerebral cortex.
Insular cortex: hiding in the lateral fissure.Where gustatory info enters cerebral cortex.
The Forebrain: Basal Ganglia
A collection of nuclei in the forebrain. They regulate intentional movements, motivation, reinforcement learning, and habits. Inputs come from all over the forebrain.
The Forebrain: Limbic System
A collection of subcortical brain areas that regulate emotions and the formation of episodic memories. Principal areas include hippocampus (critical for explicit memory formation), amygdala (critical for processing emotion, especially fear), and cingulate cortex (large area that overlies the corpus callosum, interconnects many limbic areas of the brain).
Meninges
The brain and spinal cord are wrapped by 3 protective layers of tissue called meninges. 3 types that surround the CNS:
1) The outer layer is dura mater - thick, tough, unstretchable tissue.
2) The middle layer is the arachnoid membrane - web-like extensions that create a soft, spongy layer that is filled with cerebrospinal fluid.
3) The third layer is Pia mater - sits closest to the brain and is a bit like Saran-Wrap.
The Ventricles of the Brain and CSF
Brain lots in cerebrospinal fluid (CSF) - CSF is made from blood by tissue called choroid plexus, which are in each of the brain’s 4 ventricles (the interconnected hollow spaces in the centre of the brain). CSF is made continuously and is fully exchanged about 4 times per day. It circulates around and into the brain providing nutrients and removing waste. CSF exits the CNS by passing through holes in the dura matter, where it is absorbed into blood supply.
The 4 ventricles of the brain
1) The two large ventricles sit underneath the cerebrum (cerebral cortex)
2) The third ventricles lies between two thalamic nuclei at the centre of the brain
3) The fourth ventricle is in the hindbrain, between the pons and cerebellum
4) The central canal of the spinal cord connects to the fourth ventricle.
Brain Development
A hallow, enclosed neural tube forms during the first month of human development in the womb. The first cells in this tube are neural progenitor cells. Up until the 8th week of development, these cells only undergo symmetrical cell division (each cell becomes two neural progenitor cells). Asymmetrical cell division starts around the 8th week of development. Over the next 3 months, when a neural progenitor cell divides, one of the daughter cells migrates away from the centre of the neural tube. The next time that cell divides, it will produce either two neurons or two glia cells. By end of the fifth month, there are 85 billion neurons in the brain (the most we ever have). Many of these neurons die before birth.
Photographing the Living Human Brain - Computerized Tomography (CT scan)
Relatively cheap and fast, but the resolution is not great for soft tissue like brain. A computer assisted X-ray procedure is used to take a “photograph” of the brain. Patient places their head in the centre of a large cylinder. An X-ray beam is projected through the head to an X-ray detector. The X-ray beam is delivered from all angles. A computer translates the info received into a series of pictures.
Photographing the Living Human Brain - Magnetic Resonance Imaging (MRI)
Uses a strong magnetic field and radio waves (instead of X-rays). Patient lies in a large cylinder, and a strong magnetic field is applied to the body, which causes the proton of every hydrogen atom in the body to orient in a particular direction (in line with magnetic field). While in the scanner, radio waves are administered to the body. This energy is absorbed by protons, changing the direction they are facing. But each protein immediately flips back to the position determined by the magnet. When this happens, the protons emit their own radio waves, which are detected by the scanner. By triangulating where radio waves came back from, the scanner provides an estimate of the relative density of hydrogen atoms throughout the body. Since hydrogen atoms are especially prevalent in fat, MRI provides a high spatial resolution, 3D image of the brain, which is mostly fat (myelin).
A variation of the MRI technique - Diffusion Tensor Imaging (DTI)
An MRI technique that measures the direction and speed of the diffusion of water molecules. Used to identify axon tracts. Colours indicate the direction of water molecule diffusion.
Functional Magnetic Resonance Imaging (fMRI)
fMRI uses a rapid series of MRI scans. The amount of oxygen in blood distorts the local magnetic field. WE can infer the movement of oxygenated blood around the brain by rapidly collecting a series of images and measuring the movement of these magnetic field distortions over time. Popular because it doesn’t involve needles, surgery, or radioactivity.
Recording Neural Activity in the Human Brain - Positron Emission Tomography (PET)
Involve injecting a person with a radioactive compound. Radioactive sugar molecules (like 2-DG) are commony used to detect changes in energy use in the brain. 2-DG is not broken down as easily as glucose, so it stays around for hours. The scanner identifies where reactive 2-DG molecules are located over time. Main disadvantage is their operating costs.
Recording Neural Activity in the Human Brain - Macroelectrodes
An EEG is a measure of electrical activity in the brain that uses macro electrodes (metal discs) attached to the scalp. It records the summed population-level activity of millions of neurons. It can be used as diagnostic tool.
Experimental ablation
Involves the removal or destruction of a portion of the brain. The functions that can no longer be performed following the surgery are probably controlled by that brain region.
Experimental Ablation: Radiofrequency Lesions
Small lesions can be made by passing radiofrequency current through a metal wire that is insulated everywhere but the tip. This electric current produces heat that burns cells around the tip of the wire. The size and shape of the lesion is determined by the duration and intensity of the current. A downside: axons just passing through will also be burned.
Experimental Ablation: Excitotoxic lesion
Brain lesion produced by injection of a glutamate receptor agonist such as kainic acid. These drugs cause so much excitation that the affected neurons undergo apoptosis, whereas axons just passing through are usually spared.
Experimental Ablation: Sham lesion
“Placebo” procedure that duplicates all steps of producing a brain lesion except for the step that causes extensive brain damage.
Experimental Ablation: Reversible lesion
A temporary brain “lesion” can be achieved by injecting drugs that block or reduce neural activity in a given region. Common drugs: voltage-gated sodium channel blockers, GABA receptor agonists.
Recording Neural Activity: Microelectrodes
The most direct measurements of neural activity are made with metal wires placed in the brain. Microelectrodes are thin metal wires with a fine tip that can record the electrical activity of individual neurons. Chronic electrical recording are made over an extended period of time. Acute recordings are made over a relatively short period of time.
Manipulating Neural Activity: Electrical stimulation
Involves passing an electrical current through a wire inserted into the brain. This will affect everything in the area. Very fast stimulation frequencies counterintuitively produce the same behavioural effects as lesioning the brain area.
Manipulating Neural Activity: Chemical stimulation
Achieved with drugs. Anesthetics can be injected to shut down all neural activity. Alternatively, receptor agonist/antagonist can be used, which should not affect fibres of passage since there are no neurotransmitter receptors in the middle of an axon.
Manipulating Neural Activity: Optogenetics
Use of light to control neurons that have been made sensitive to light through the introduction of foreign DNA. This foreign DNA provides instructions to make light-sensitive proteins. Proteins that are activated by light are called opsins.
Virus
A small infectious agent that replicates by injecting its DNA into normal cells. Virus DNA is the instructions for how to make more virus.
Viral-Mediated Gene Delivery
We know how to remove the DNA from a virus, which renders the virus replication-deficient”. We can also add foreign DNA to a virus. When a modified virus is injected into an animal’s brain, it will infect all the cells in the area. Once a virus gets its DNA into the nucleus of a cell, that cell will start to transcribe the viral DNA and make the associated proteins.
Tracing Neural Connections: Retrograde labeling
Trading afferent axons. Used to label the cells that project to a given region. Various chemical such as fluorogold can be used as retrograde tracers. Fluorogold is taken up by axon terminals and transported back to the cell body.
Tracing Neural Connections: Anterograde labeling
Tracing efferent axons. Used to label where axons from particular location go to. Various chemical such as PHA-L can be used as anterograde tracers. PHA-L is taken up by cell bodies and transported down to axon terminals.
Stereotaxis Surgery
A surgical intervention that uses a stereotaxic apparatus. We can put something (drugs, viruses, or tracers) into a very specific part of the brain. Also used to permanently implant things.
Bregma
The junction where pieces of skull fuse together. Bregma is often used as a reference point of stereotaxic brain surgery.
Common Reasons for Stereotaxic Surgery
Commonly used for one-time infections of drug or virus to: lesion a brain area, lesion a specific type of cell in a particular brain area, change gene expression.
Measuring Neurotransmitter Levels - Microdyalisis
Old-fashioned approach. Microdialysis used to be a popular technique for measuring changes in neurotransmitter levels in a brain region in behaving animals. A dilute salt solution is slowly infused into the microdialysis tube, where it picks up molecules that diffuse in from the extracellular fluid. The contents of the fluid are then analyzed.
Measuring Neurotransmitter Levels: Man-made fluorescent reporter proteins
Scientists now use viral-mediated gene delivery to get neurons to express man-made fluorescent sensors, which allow us to visualize neurotransmitter release in a living brain.
