Psych 115 Midterm 1 UCLA

What are the three layers of protective layer called?

Meninges

- Dura Mater (thick outer layer)

- Arachnoid (Spongy middle layer)

- Pia Mater (thin inner layer)

What is the organ that constantly manufactures the CSF?

choroid plexus, which resides in hollow tubes and cavities called ventricles

Where does the action potential originate?

Integration zone (or active zone)

What are the three types of neurons?

Multipolar - with multiple dendrites coming off the soma

Bipolar - just 2 processes sticking off soma

Unipolar - just one extension form soma that branches off into two

How do excitatory, inhibitory, and modulatory neurotransmitters differ?

excitatory - depolarize post synaptic neuron and increases likelihood of post synaptic action potential

inhibitory - hyperpolarize post synaptic neuron and decreases likelihood of AP

modulatory - has multiple effects on post synaptic target

What is the difference between efferent and afferent?

efferent - output

afferent - input

What is the potential equation for a voltmeter?

V = C+ - C-

What is the driving force on a molecule and when is it zero?

- Sum of both electrical force (determined by charge of membrane & ion) & chemical force (determined by concentration gradient) acting on ion

- its zero either when both forces are zero OR when they are equal and opposite

What are the approximate equilibriums for each molecule?

Ek = -80mV

ENa = +60 mV

ECl = - 90 mV

ECa = +120 mV

How do IPSPs work?

Inhibitory Post-Synaptic Potential - when an inhibitory transmitter such as GABA is released from synapse and binds to receptors such as ligand gated chloride channels which make membrane potential more negative which leads to hyperpolarization of membrane preventing it from making an action potential

How do EPSPs work?

Excitatory Post Synaptic Potentials - when the excitatory neurotransmitter (glutamate or acetylcholine) is released & binds to ligand gated sodium ion channels which depolarizes cells and makes it more likely to fire AP

What is the passive propagation of the EPSP?

When the EPSP gets smaller as it travels from the synapse to the axon hillock (integration zone)

How can spatial summation and temporal summation help with the passive propagation of the EPSP?

Spatial summation - if two presynaptic neurons fire simultaneously the two EPSPs will sum to create a larger EPSP

Temporal Summation - creation of large EPSP from two smaller EPSPs occurring in rapid succession at a single synapse

Why is an AP called an "all or none" phenomenon?

As soon as membrane is depolarized above spike threshold, an AP will occur.

- This is because opening voltage gated sodium channels will allow sodium to enter and depolarize membrane, which opens ever more channels (positive feedback cycle)

How do the 4 protein subunits that make up the voltage gated sodium channel influence its 3 different states?

Physical configurations of subunits change for each state

Closed - Na+ cannot pass through pore, when cell is hyperpolarized

Open - Na+ ions can flow freely, happens when depolarization occurs, but quickly switches to inactive after millisecond

Inactive - Na+ cannot pass through pore, channel cannot be opened even if depolarized, must go back to closed state through hyperpolarization before another AP

What is the role of the delayed rectifier channels?

Open at -45mV to help potassium ions get out faster, they open slowly to allow spike to reach its peak

-only has 2 states, open (when membrane depolarized above delayed rectifier threshold) and closed (when below threshold)

After sodium moves into cell and potassium moves out because of the AP, how do they go back to equilibrium?

Na-K ATPase Pump which ejects 3 sodium ions for each 2 potassium ions imported, which repolarizes membrane at the end of AP

What is the difference between active and passive transport?

Active - required ATP an pushes ions in the direction it wants REGARDLESS OF DRIVING FORCES

Passive - ion channels open or close to allow ions to flow according to electrochemical gradient in direction of driving force

Which factors contribute to the ending of the action potential

- Na-K ATPase Pump

-Delayed Rectifier K+ channel

- Inactivation of Sodium channels

- Leak K+ channels

What is the difference between the central and peripheral nervous systems?

Central Nervous System - includes brain and spinal cord, group of neurons in CNS called nucleus

Peripheral Nervous System - includes spinal and cranial nerves that relay sensory & motor info to & from CNS, group or cluster of neurons on PNS called ganglion

What is the role of the Dorsal root ganglion?

DRG unipolar neurons in PNS whose job is relay somatosensory information from skin to spinal cord

How do local anesthetic drugs work?

They block somatosensation by blocking active zone sodium channels in skin

What does active propagation look like? And where does it occur?

IT happens in unmyelinated axons and they have sodium and delated rectifier channels all the way down axon so there is a repeated AP all down axon, but very slow

What is saltatory conduction? and Where does it occur?

Happens in myelinated axons which reduces passive attenuation (reduction of AP), have gaps in myelin called nodes of Ranvier which have high density of active sodium and delayed rectifier channels in membrane, which gives it a boost to get to the next node

What is passive propagation and where does it occur?

It happens in axons without active channels and the AP propagates very fast but not very far

Where does myelin come from?

Myelin Sheath made by glial cells

-in PNS made by Schwann cells

-in CNS made by Oligodendrocytes

where dense population of myeline called white matter, with little myelin called gray matter

What is multiple sclerosis caused by?

loss of myelin in CNS, cause is unknown but theorized that is autoimmune or apoptosis of oligodendrocytes

What happens in the synaptic bouton?

Voltage gated calcium channels opened by AP which causes calcium to flow (into cell?)

How does the presynaptic action potential cause vesicles to fuse with membrane?

1. neurotransmitter manufactured by neuron

2. NT pumped into vesicles by vesicular transporters

3. Filled vesicles move toward cell membrane and waits for AP

4. When AP occurs, calcium enters synaptic bouton and causes vesicle to fuse with membrane and dump NT into synapse

5. Clathrin coat forms on inner surface of membrane and pinches a new empty vescile from cell membrane

6. New vesicle sheds its coat and starts filling up with NT again

What are the steps in chemical neurotransmission?

-NT travels to postsynaptic target cell & binds to receptors

-NT unbinds to receptor and is degraded (catabolized) or reabsorbed into cell (reuptake)

What are the two major categories of neurotransmitters?

1. Small molecule NT are modified amino acids (also includes choline)

2. neuropeptides which function as hormones to send signals over long distances are small protein molecules

What are some examples of small molecule neurotransmitters?

Amino Acids:

GABA - inhibitory

Glycine - inhibitory

Glutamate - excitatory

Aspartate - excitatory

Biogenic Amines:

Dopamine - modulatory

Adrenalin/Noradrenaline - modulatory

Seratonin - Modulatory

Histamine - Modulatory

NOT synthesized from Amino Acids:

Acetylcholine - excitatory/modulatory

What is glutamate?

Dominant excitatory neurotransmitter in brain

Synthesized from AA glutamine by enzyme glutamine aminohydrolase

What is GABA?

Gamma-amino-butyric Acid is dominant inhibitory neurotransmitter in CNS

Synthesized from Glutamate by enzyme glutamate decarboxylaze (GAD) by removing CO2

Which neurons produce glutamate, inhibitory or excitatory?

BOTH! the only difference between them is whether they express gene for GAD

Why does glutamate excite while GABA inhibits?

They bind to different receptors

What is the difference between metabotropic and ionotropic receptors?

Ionotropic - ligand gated channels that are opened by neurotransmitter binding to make membrane more permeable to ions

Metaotropic - G-protein coupled receptors that are activated when neurotransmitter binds to extracellular domain which causes linked G-protein to be released from intracellular domain of receptor protein & float through cytoplasm until it binds to various targets

What are examples of Glutamate receptors being both ionotropic and metabotropic?

Ionotropic (ligand gated ion channels permeable to both sodium and potassium that produce fast EPSP)

- AMPA

- NMDA

- Kainate

Metabotropic

- Group I (mGluR1, mGluR5)

-Group II (mGluR2, mGluR3)

- Group III (mGluR4, mGluR6, mGluR7, mGluR8)

What are examples of GABA receptors being both ionotropic and metabotropic?

Ionotropic (ligand gated chloride channels which produce fast IPSPs)

-GABA-A

- GABA-C

Metabotropic (G-protein couple receptors that activate potassium channels that produce slow IPSPs)

-GABA-B

What are some features of Ionotropic GABA receptors?

-GABA-A receptors are ligand gated Cl- channels

-produces fast IPSP

-GABA receptor made of 5 different subunits, which different drugs can bind to each subunit

-each subunit is one of three types (alpha, beta, or gamma)

What is the difference between endogenous and exogenous ligands?

endogenous - chemicals normally found in the body which bind to the receptor

Exogenous - compounds not found in body that when introduced can affect receptor as an agonist (activate it the same way as normal endogenous ligand) or antagonists (prevent it from being activated by its normal endogenous)

What are the two modes of drug-receptor interaction?

1. competitive binding - drug attaches to receptor and blocks normal ligand binding cite

2. noncompetitive binding - drug attaches to receptor and prevents it from being activated, it does not block normal binding cite, but not longer allows ligand to activate it

What are some examples of GABA agonist drugs? And how do these drugs work?

GABA-A Agonists:

- benzodiazepines (valium, ambien, Xanax, versed)

-barbiturates

-alcohol (ethanol)

-anti-seizure drugs

These drugs work by increasing inhibition & depressing activity in nervous system (lower doses produce relaxation, higher doses induce sleep, very high doses can stop breathing)

What was the contribution of Theodore Schwann?

first to propose that all things came from cells

discovered schwann cells that make myelin in PNS

How did Golgi & Ramon y Cajal's theories differ?

Golgi - Reticular theory that neural system was like plumbing and all cells connected to each other

Neuron Doctrine - brain more like drive through consisting of individual cells separated by small gaps (proven in 1950)

What was Otto Loewi's contribution?

neurons communicate through neurotransmitters

- discovered this by cutting the vagus nerve, which releases neurotransmitter - acetylcholine- that slows heart beat, of one heart, but it was still slowed by a second nearby heart that was still releasing the neurotransmitter

Who discovered the first EEG?

Electron encephalography was discovered by Hans Berger who put sensors on scalp to read electrical currents

What was John Eccles' contribution?

1st synaptic recordings in central nervous system

Discovered EPSPs & IPSPs by being the first to see how voltage works in synapse

What are some examples of catecholamines and what AA are they synthesized from?

Synthesized from AA tyrosine

1. Dopamine (tyrosine --> (tyrosine hydroxylase) L-DOPA --> (amino acid decarboxylase) Dopamine)

2. Norepinephrine (Dopamine --> Norepinephrine by b-hydroxylase)

3. Epinephrine (norepinephrine --> (phenylethanolamine-N-methyltransferase) epinephrine/adrenalin)

Where is dopamine made and how?

Tyrosine catalyzed into L-DOPA by tyrosine hydroxylase, then converted into dopamine by amino acid decarboxylase

- made by neurons whose cell bodies are located in ventral tegmental area (VTA) or substantia nigra

- also made in retina & by small group of cells in hypothalamus

What are the two projection systems of dopamine?

1. Mesolimbocortical projection originates from dopamine neuron in VTA which sends axons to cortex (esp frontal), hippocampus, and nucleus accumbens

2. Mesostriatal projection from dopamine neurons in substantia nigra which sends axons to caudate nucleus (striatum) & globus pallidus

What are some of the diseases that are a result of a dysfunction of dopamine?

- Parkinson: caused by death of dopamine neurons in substantia nigra which causes mesostriatal dopamine pathway to degenerate

- Schizophrenia: hypothesized to involve dysregulation of dopamine inputs to prefrontal cortex

-Tourettes: overactivation of dopamine pathways

-Drug Addictions: caused by stimulating mesolimbocortical dopamine pathways

-Major Depression: inhibition of dopamine signaling

What are the two main families of dopamine receptors?

1) D1 family: G-proteins are couple to alpha subunit that excite production of 2nd messenger (cAMP) by adenylyl cyclase

2) D2 family: G-protein couple to alpha subunit that inhibit production of 2nd messenger cAMP by adenylyl cyclase

How do D1 receptors work?

Alpha subunit excitescAMP production, which activates protein kinase A (PKA) which phosphorylates proteins by adding phosphate to them, switching on enzymatic function, which causes a downstream effect to excite neuron causing

- calcium channel activation

- potassium channel inhibition

- enhancement of NMDA receptor currents

How do D2 receptors work?

Alpha subunit of D2 receptors inhibit cAMP production which reduces activation of PKA, blocking excitatory downstream effects of PKA

-Beta & Gamma subunits also inhibit neuron by

- opening potassium channels

- closing calcium channels

Where does norepinephrine and epinephrine come from?

-Norepinephrine is synthesized from dopamine by dopamine beta-hydroxylase

-Norepinephrine is converted into epinephrine (adrenalin) by an additional chemical synthesis step

Where is Norepinephrine released from?

-made and released by neurons whose cell bodies reside in locus coeruleus and lateral tegmental areas, which send axons to many other brain regions

- also released from adrenal glands into bloodstream to regulate automatic nervous system

How does norepinephrine effect the body?

Participates in controlling arousal and attention

- low NE levels are associated with sleep

- medium NE levels are associated with waking and vigilance

- high NE levels are associated with anxiety and distractibility

What are the two families of Adrenoreceptors?

1. Alpha family: g-proteins coupled to 2nd messenger to produce inhibition of post synaptic cell or trigger release of calcium from intracellular stores

- alpha-adrenergic antagonist drugs used to lower BP in hypertension patients

-alpha-adrenergic agonist drugs used as decongestants, pupil dilators, and to increase BP

2. Beta family: g proteins excite postsynaptic cell

- Beta adrenergic antagonist drugs "beta-blockers" can be anxiolytic

- Beta adrenergic agonist drugs used in inhalers but have side effects such as hyperactivity, attention deficit, and panic attacks

What do transporters do?

-A transporter is a protein complex that pushes molecules from one side of cell to another through active transport

How do drugs create their effect on people?

amphetamine, ritalin, and cocaine act on membrane transporters for catecholamine neurotransmitters

-increase availability of dopamine, noradrenalin, and adrenalin by blocking reuptake

What are the three ways that catecholamine reuptake inhibitors work?

1. competitive antagonism - transporter sucks up drug not NT, preventing NT from reuptake

2. noncompetitve antagonism - causes transporter to be internalized into presynaptic cell membrane so it is not longer removing NT from synapse

3. Reversal - causes transporter to reverse direction and push NT in in opposite direction across membrane

How is serotonin (5-HT) made?

synthesized from amino acid tryptophan

-produced in neurons located in raphe nuclei and sends axons to diff areas of brain

What are some of the features of 5-HT receptors?

- 7 families of receptors

- all are metabotropic excite 5-HT3 which is a ligand gated cation channel permeable to sodium and potassium

-Some are selective serotonin agonists which bind very specifically to 1 receptor (Busiprone is a 5HT1A agonist used for anxiety & depression)

-Nonselective serotonin agonists (LSD)

- Selective Serotonin Reuptake inhibitor (SSRI) ex. Prozac as antidepressant

-Nonselective serotonin reuptake inhibitor (NSRI) - ex MDMA, ecstasy

How is acetylcholine made & where is it released?

Synthesized by combining choline with acetate (acetyl-coA) which is done by choline acetyltransferase

- released by neurons with cell bodies in basal forebrain (nucleus basalis & medial septum)

What are the two types of Acetycholine Receptors?

1. Nicotinic receptors: ligand gated cation channels

2. muscarinic receptors: metabotropic receptors linked to voltage gated-potassium channels

How do nicotinic Acetylcholine receptors?

Peripheral nervous system acetylcholine ex excitatory neurotransmitter release by motor neurons to activate muscle fibers at the neuromuscular junction

-Nicotinic Agonists: nicotine

-Nicotinic antagonists: curare, various muscle relaxants

How do muscarinic Acetylcholine Receptors?

-distributed throughout CNS and PNS

-Muscarinic agonists: muscarine nerve toxin found in poisonous mushroon

-Muscarinic antagonists: atropine used surgical anesthesia and to treat bradycardia (slow heart rate); scopalamine is used in low doses to treat motion sickness

What are endogenous Opiates?

peptides (small proteins) manufactured by presynaptic neurons

What are the 3 types of opioid receptors?

1. Mu - causes analgesia, euphoria, addiction

- Endo Ag: endorphins, enkaphalins

-Exo Ag: morphine, fentanyl

-Exo Anta: naloxone, naltrexone, oxycodone, hydrocodone

2. Kappa - analgesia, sedation, dysphora

- Endo Ag: dynorphins

- Exo Anta: oxycodone, nealtrexone

3. Delta - analgesia

- Endo Ago: endorphins, enkaphalins

- Exo Ag: morphine, codeine, hydrocodone

What are some of the characteristics of endocannabinoids?

- Exogenous ligand: THC

- Endogenous ligand: AEA & 2-AG

- lipid molecules

- retrograde transmitters (post --> pre)

- not "true" NT but paracrines

What are the two types of endocannabinoid receptors?

Both g-protein, found on presynaptic terminal, bidn to AEA & 2-AG from post-synaptic

1. CB1 - activation inhibits calcium influx & inhibits release of NT

2. CB2

Why are proteins described as molecular machines?

- every cell body makes thousands of different protein which are assigned to specific jobs

- some work inside cell & others secreted from cell to rest of body

Ex. of proteins

immunoglobulin G - binds pathogens protect infection

Hemoglobin - store oxygen in RBC

Insulin -metabolize sugar in pancreas

Adenylate cyclase -catalyze ATP into cAMP

Glutamine Synthetase -deactivates glutamate to form glutamine

What do neuronal proteins do and what are some examples of them?

-neuronal proteins are elements of neuronal phenotype

Examples:

- synapsin: docking & fusion of NT vesicles in bouton

-Voltage Gated sodium channels: generate AP by allowing sodium into cell

-Dopamine transporter: push dopamine NT into cell after released

-Glutamate decarboxylase: catalyzes conversion of glutamate into GABA

Who is responsible for making proteins?

Ribosomes translate RNA into proteins

- assembles peptide chain in sequential order specified by messenger RNA

1. Nuclear DNA translated to make mRNA

2. mRNA leaves nucleus to moves to ribosome to be translated into chain of AA

What is a transcription factor and what does it do?

- They are little marking stickers that bind to promoter sequence so cell will read it

-Bind to DNA promotor sequence

What determines a neuron phenotype?

the proteins it transcribes, which is determined by which mRNA is translates, which is determined by which gene it expresses

What is the SCN9A gene encode for? and How is it an example of naturally occurring mutations?

-encodes for protein NAv1.7 which makes up voltage gated sodium channel in the dorsal root ganglion

-a family if pakistan carries a heritable mutation which causes sodium channels with Nav1.7 to become non-functional therefore they don't experience pain

What is genetic engineering?

deliberately introducing mutations into an organism

which can happen through forward or reverse genetics

What are the steps to forward genetics?

1. introduce organisms to mutagen

2.screen to look for mutagenic phenotypes

3. perform additional studies to determine which specific mutations are responsible for interesting phenotype

What are the different Reverse Genetics?

Producing targeted and deliberate mutations of a specific gene

1. Gene knockout - remove gene from organism

2. Gene knock in -add gene to organism

3. Gene editing - modify nucleotide sequence of gene to change AA

What is pronuclear injection of a transgene?

transgene: gene that is artificially transferred from one species to another

-inject transgene into fertilized egg and implant egg into uterus of mouse

How is GFP used for determining gene expression

Knock in Green Flourescent protein into mice to see which genes cause it to glow in the dark

How can promotors be used to determine gene expression?

link promoter of certain cell types to a transgene of GFP to see which ones light up

What is neuron-specific expression?

When you control which cells a gene is expressed in and attach it to a cell-specific promoter sequence

(ie excitatory neurons attached to GFP & inhibitory neurons attached to red flourescent protein)

What are DREADDs?

Design Receptor Activated by Designer Drugs

- "designer drug" clozapine-N-oxide doesn't bind with any receptors but created designer receptor, which allows us to control CNO to excite or inhibit

What was channelrhodopsin used for?

Since it is ionotropic light receptor (optically gated channel), inject into mammalian neuron to optically control neural activity

- YFP-tagged channelrhodopsin: blue light open channel excite, green light makes channel glow

-ectopic expression of channel rhodopsin-2

What are the three types of optogenetic transgenes?

1. channelrhodopsin- sodium channel sensitive to blue light causing depolarization

2. Halorhodopsin - chloride pump sensitive to yellow light causing hyperpolarization

3. Archaerhodopsin - proton pump sensitive to green light causing H+ ions pumped out hyperpolarizing cell

What are the six stages of neural development?

1. Neurogenesis

2. Cell Migration

3. Differentiation

4. Synaptogenesis

5. Neuronal Cell Death

6. Synapse Rearrangement

What are the three layers of the embryo? What do each of them eventually grow into?

Endoderm - stomach, colon, liver, pancreas, bladder, trachea, lungs, intestines

Mesoderm - muscle, bone, cartilage, fat tissue, blood vessels

Ectoderm - nervous system and skin

What are the steps to neurogenesis?

Birth of cells that become neurons

1.Ectoderm cells are pluripotent & have many fates (skin or nerve)

2. Neural plate are multipotent could become neuron or glial in nervous system

3. Neural plate divides into precursor cells: glial and neuronal

4. Glial precursor cells divide to become glia and neuronal precursor cells divide to become neurons

What are the three subdivisions of the neural tube that it eventually develops in to?

Forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon)

Forebrain later develops into telencephalon and diencephalon

What do the terms ipsilateral, contralateral, dorsal, ventral, posterior, anterior, sagittal, coronal, rostral, caudal, medial, lateral?

Ipsilateral - on the same side as

Contralateral - on the opposite side from

dorsal - back and top of head

ventral - stomach and face

Anterior - front when walking

Posterior - back when walking

Sagittal - cuts left from right

Coronal - cuts front from back

Rostral - toward nose

Caudal - toward back

Medial - toward middle

Lateral - away from middle

What happens in stage 2 of neural development?

Cell Migration

-central canal becomes ventricles

-surrounding canal is ventricular zone

-outer region on neural tube = marginal zone

-ventricular zone divide to create new cells

- once chosen fate, migrate from ventricular zone to marginal zone to form brain and spinal cord

-radial glia provides railway for migrating cells

-neurons travel from ventricular zone to marginal zone

What are the major factors that determine neuronal cell fate in stage 3?

1. time of birth - brain develops inside out (early becomes deep layers, later becomes surface layers)

2. cell to cell signaling - send neurotrophic factors, cell adhesion molecules, hormones, NT to influence other cells fate

What happens during stage 4 of neuronal development?

Neurons extend growth cones which become axons & dendrites (synaptogenesis)

How do chemical signaling influence synaptogenesis?

Outgrowth of neurites excited or inhibited by neurotrophic factors

1. Nerve growth factor - produced by target taken up by axons on innervating neurons keeping them alive

2. Brain-derived neurotrophic factor

What happens during stage 5 of neural development and what causes this?

Neuronal cell death (except in olfactory, epithelium, and dentate gyrus)

- neurons compete for neurotrophic factors and without enough they die

What happens in the 6th and final stage of neural development?

Pruning of synapses

What are all the roles of neurotrophic factors in neuron development?

- stimulate growth of dendrites and axons

- influence cell fate (differentiation)

- influence cell death

-influence pruning