Lecture 1 (chapter 2) Flashcards
Cellular Components and Functioning
Intracellular Components and Functions
• Cell membrane
• Nucleus: Contains chromosomes and nucleolus (where DNA is stored)
• Ribosomes (packages things)
• Smooth and rough endoplasmic reticulum:
o Rough: Contains ribosomes that produce proteins to be transported within and out of the cell
o Smooth: production of lipids and transports proteins
• Mitochondria: Produces adenosine triphosphate (ATP), which the cell uses as an energy source
• Golgi complex: Assembles and package proteins to be sent to other destinations
• Cytoskeleton: Strands of proteins maintain the internal structure of a cell
• Synaptic vesicles
• Dendrites: branches coming out of cell body with one long one called the axon which connects cells and allows for neurotransmission.
• Axon Damage: if It severed it can stop communication between cells; characteristic of Alzheimer’s disease – the main reason people get Alzheimer’s is that their axons start breaking apart.
• Axons connect to another cells dendrites where molecules are released and information is transmitted to the other cell.
*How many connections are in the brain 100 trillion connections. This makes it so much
harder to identify what is going on in the brain, identify, explain, and treat problems.
cell structure
• Strands of proteins maintain the internal structure of a cell (cable) by forming the cytoskeleton
• Large strands are known as microtubules, and they extend from the cell body through the axon to the terminal bouton
o Anterograde transport
o Retrograde transport
*When the microtubules are dysfunctional the connections between cells are reduced
Terminal boutons
- Contain vesicles filled with substances that are released nearby other cells
- Dendrites are treelike structures that emerge from the cell body of the neuron and receive messages from other neurons
- Located on the dendritic branches are protrusions known as dendritic spines
Dendrites and synapses
• Each dendrite receives thousands of inputs from other neurons via synapses
• Synapse: Site at which axons make functional contact with their target cells
o Space between the terminal bouton of a neuron sending a message and the area of a neuron that is receiving the message (molecules transmitted across the cell; treatment reduces or increases neurotransmitters binding to the synaptic cleft and releasing; dopamine, serotonin, acetylcholine etc.)
Types of synapses
Axons which connect to…
- Axosecretory
- axon terminal secretes into BLOOD
VESSEL - Axoaxonic
- axon terminal secretes into ANOTHER
AXON - Axodendritic
- axon terminal connects to DENDRITE
SPINE - Axoextracelluar
- axon terminal secretes into
EXTRACELLULAR FLUID - Axosomatic
- axon terminal secretes on SOMA
- Axosynaptic
- axon terminal secretes on another
AXON TERMINAL
*Point is that cables carry information to different areas of the cell body and these complex connections create the neural circuit.
Synapse
- Terminal bouton of the neuron: Presynaptic
- Space between presynaptic and postsynaptic neurons: Synaptic cleft
- Neuron that receives the message: Postsynaptic
*Releases neurotransmitters from terminal button into presynaptic cell
into synaptic cleft. Will bind to the postsynaptic cell and if reaches
excitatory threshold will cause the neuron to fire (change from
receptor to transmitting neuron) all occurs at the molecular level.
Action potential
Action potential
• Negative and positive particles called ions are unevenly distributed in the intracellular and extracellular fluid
• The intracellular fluid contains more potassium ions (K+) than the extracellular fluid and smaller amounts of chloride (Cl−) and sodium (Na+) ions
o Positive ions outside the cell (Na+ and K+) are attracted to the intracellular fluid however the negative ions such as Cl− are repelled by the negative charge of the intracellular fluid
o This attraction between positive and negative ions and the repulsion between like-charged ions produce energy in the form of electrostatic pressure (energy source to allow diffusion when channels open)
• An action potential lasts less than 1 millisecond until neurons are quickly restored to the resting potential
What we need to know:
• Neurons are a unit of information which primary function is to pass it to another cell. It is passed by molecules (i.e., neurotransmitters) released from presynaptic terminal button into synaptic cleft, they bind to receptor site in the postsynaptic neuron (site varies), if the excitatory threshold is met an action potential occurs and channels in the cell membranes open and allows (diffusion and __ energy) +/- to enter and exit the cell. Refractory period where more than -70 charge in cell where no communication can occur. K+ ions coming into cell and –ions leaving the cell depolarizes the cell (reduce – charge to 70) at its resting cell potential.
• Action potential = receptor channels open, ions are passed, that excitatory threshold is met and action potential to occur.
• Opposite charges attract, + in extra attracted to – charge of intra; this changes the charge.
Neurotransmitters
Chemicals found in the brain are considered to be a neurotransmitter if:
- Are synthesized in neurons
- Are released, occupy a receptor, and result in an effect in another cell
- Are cleared from the synaptic cleft following release
- Effects can be replicated by an experimental substance
Neurotransmitter classes
- Transmitter gases
- Large molecule transmitters: Molecular weights from 200 to 5,000
- Small molecule transmitters: Molecular weights less than 200
- Transmitter substances are unequally distributed throughout the brain
Glutamate
Glutamate
• Principal excitatory neurotransmitter
• Glutamatergic neurons are widely distributed
• Glutamate receptors are usually located on parts of the dendrite
• Glutamate is cleared from the cleft primarily by glia cells
• Glutamate is also reclaimed from the synaptic cleft by transporter proteins located on the presynaptic neuron
Glutamate imbalance linked to:
o Learning and memory
o Bipolar disorder and mania
o Schizophrenia
o Depression
Gamma-Amino Butyric Acid (GABA)
Gamma-Amino Butyric Acid (GABA) • Principal inhibitory neurotransmitter in the brain • Widely distributed throughout the brain Implicated in: o Epilepsy o Tourette’s disorder o Anxiety disorders o Neurodegenerative disease o Post-traumatic stress disorder (PTSD) o Alzheimer’s disease o insomnia
Monoamine neurotransmitters
Monoamine neurotransmitters
• Catecholamines
• Dopamine (DA)
• Epinephrine (EP)
• Norepinephrine (NE)
• Indolamines
• Serotonin
• Melatonin
*Conditions are treated with medication to make molecular changes that target the release of
neurotransmitters. It is common for people to treat disorders with medication without
understanding what effects it is having on the persons brain chemistry and subsequently the
person themselves. We treat people without understanding what it does.
Transmitter gases
• Easily cross the cell’s membrane, diffuse across the cleft, and enter other cell membranes
• Short-lived
• Examples:
o Hydrogen sulfide (H2S): Role in the release of hormones from the hypothalamus
o Carbon monoxide (CO): Regulates olfactory and hypothalamus neurons
o Nitric oxide (NO): Learning and memory
Large molecule neurotransmitters
• Peptides that consist of two or more amino acids connected by peptide bonds
• Examples:
o Angiotensin
o Cholecystokinin
o Somastostatin
o Oxytocin: Modulatory effect on pain perception
Small molecule neurotransmitters
- Amino acids: Aspartic acid, gamma-aminobutyric acid (GABA), glutamate, and glycine – Major transmitters in the brain
- Monoamines:
o Catecholamines: i.e. Dopamine, epinephrine, noreepinephrine
o Indolamines: i.e. serotonin - Acetylcholine
Aspartate
G…..
• Abundant in the brain
• Excitatory effect
• Aspartate and glutamate are synthesized in the terminal bouton
• Receptor dysfunction for both amino acids has been implicated in schizophrenia
o Ketamine, a drug that blocks glutamate receptors, produces schizophrenia-like symptoms in healthy adults
Dopamine
High levels in…
What effect can it have?
What breaks it down?
Dopamine
• Concentrated in the basal ganglia, substantia nigra, and tegmentum and have widespread projections to the frontal regions of the brain (produced in subcortical structures; cell death in the substantia nigra then we can find localized brain regions implicated in disorders like Parkinson’s disease; understanding this lets us know how to treat people with molecule and brain region to target)
• Involved in movement, attention, motivation, and learning
• Implicated in schizophrenia, obsessive compulsive disorders, Tourette’s disorder, Parkinson’s disease, and addiction Dopamine
• Depending on the receptor, dopamine can have an excitatory, inhibitory, or modulating effect on the cell. This variance in distribution of receptors is consistent with the large number of brain functions in which dopamine appears to be involved
• Dopamine is broken down by monoamine oxidase (MAO) and catechol-o-methyl transferase
Norepinephrine and Epinephrine (Adrenaline System)
Norepinephrine and Epinephrine (Adrenaline System)
• Contained in the brain stem
• Project to the hypothalamus, thalamus, and the cortex.
• Implicated in anxiety, mood disorders, ADHD, panic disorder, major depressive disorders
*We can’t regenerate dead neurons; we can manipulate
molecular chemical release in the brain. Manipulate
dosage till it has the desired effect on removing the
undesirable behaviour.
Serotonin
Serotonin
• Concentrated in the brain stem and midbrain
• Projection system is widespread
• Implicated in arousal, wakefulness, sleep, appetite and eating behavior, stress response, mood, and motor behavior
• Serotonin synthesis is substantially higher in children than adults
• Implicated in anxiety or depression
Acetylcholine
Acetylcholine
• Acetylcholine is widespread throughout the central and peripheral nervous system
• Implicated in attention, memory, learning, various psychiatric disorders, and dementias
Psychopharmacology
- Drugs prescribed to treat cognitive and behavioral symptoms of psychological/psychiatric disorders are known as psychotropic medications
- Psychotropic medications can improve cognitive and behavioral symptoms in many individuals, but they do not cure the underlying cause of psychological disorders
*They do not cure you. The reduce symptoms but cannot regenerate the dead cell/damage
already sustained. It’s the same chemistry as giving children illegal drugs.
psychotropic medication stats
o Most common medications were antidepressants and antianxiety medications
o 8 out 10 reported using the medications long term
o 20.8% of white adults reporting use of psychotropic medications versus 8.7% of Hispanic adults
o Women were more likely than men to report taking psychotropic medications
o Use increased with age (25.1% of adults aged 60–85 years versus 9.0% of those aged 18–39 years)
*Very high number of people on medication. Imbalances influenced by genetics, age, gender,
ethnicity (access to health care or genetics).
• Psychotropic medication has increased among children of all ages
Caveat to drug prescriptions!
- Despite the widespread use of psychotropic medications among children, adolescents, and adults, the precise mode action of most drugs used to treat psychiatric disorders is unknown!
- “At the molecular level an explanation of the action of a drug is often possible; at the cellular level, an explanation is sometimes possible; but at the behavioral level, our ignorance is abysmal (i.e., we know which neurotransmitter is increased or decreased but that it all. We do not know how explain how this effects their cellular functioning and behaviour; when people stop taking medication their behaviour will change because their molecular level changes have occurred by the drug)
Pharmacokinetics
• The process of drugs being absorbed, distributed, metabolized, and excreted by the body is known as pharmacokinetics