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Elements
•Substance that cannot be broken down into another substance •Oxygen, Carbon, Hydrogen, Sodium, etc.
atom
•A single unit of an element •Electrically neutral (usually) •Made of electrons (-), which orbit a nucleus –Nucleus: contains neutrons (no charge) and protons (+)
Ions
: an atom with slight change due to gaining or losing electrons (Examples: Na+, K+, Ca++, Cl-)
Ion Formation
:when atoms lose or gain an electron •Each ring (orbit) wants 2 or 8 electrons to be stable •A ring that is mostly complete is likely to take an electron •Cl- •A ring that is mostly incomplete is likely to lose an electron •Na+ •K+ •Ca++
Polarity
H electrons spend more time orbiting the Oxygen atom than each Hydrogen atom, This gives the oxygen region of the water molecule a slight negative charge, and the hydrogen regions with a slight positive charge. This difference in charges on opposite ends is referred to as a polar molecule…
Saltwater in the brain
žThe polar water molecules break down salts ž žNaCl, KCl, CaCl ž žNa+, K+, Ca++, Cl- ž žThese ions move in water
Ions Critical to Cell Function
žNa+ (Sodium) žK+ (Potassium) žCa++ (Calcium) žCl- (Chloride) ž žSalts (KCl, NaCl, CaCl2) break down in water to form ions žSaltwater is inside and outside neurons žCharged ions make up electrical activity in the brain
Cell Membrane: Barrier and Gatekeeper
Polar H20 molecules are attracted to the membrane, but cannot pass due to the non-polar (hydrophobic) fatty acid lipid layer Phospholipid bilayer
žDifferent concentrations of ions inside the cell vs. outside the cell
(Na+, Cl-, Ca++, K+) •Cannot cross the membrane •Neuron at rest: more negative inside than outside •Neuron when “firing”: more positive inside than outside
What can cross the membrane? (into/out of the neuron)
•Small molecules: –Oxygen, Carbon dioxide, Glucose •Lipids (hydrophobic, non-polar): –Endocannabinoids, THC •Steroids –Examples: Cortisol, Testosterone, Estrogen
Products made in the nucleus
žProteins: to be used in neuron functioning •Ion channels/pumps •Receptors for neurotransmitters •Enzymes for neurotransmitter formation ž žGenes/intracellular proteins that affect neuron activity (think 2nd messenger cascades) ž žNeurotransmitters or building blocks for NTs, Vesic…
What does the DNA code for?
žPortions of the DNA helix code for: •Specific receptor types •Enzymes •Specific neurotransmitters •Cellular behavior •Susceptibility to specific disease states
Chromosomes (23 pairs)1.8meters long
•Double helix structures •Contain entire DNA sequence •Always moving/changing shape By changing shape, chromosomes expose different genes to the surrounding fluid to allow for specific proteins to be formed
Genes
•Segments of DNA •Blueprints for proteins •Receptors, ion channels, etc •Estimated 20,000+ genes in human DNA •Specific cells use specific genes****
Cfos
Cfos is a type of transcription factor, and can increase or decrease synthesis of other genes. Genes for dopamine synthesis enzymes are increased by activity in dopamine neurons, Genes for certain receptors used in memory formation are increased after stimulation that leads to LTP. Cfos u…
Process of protein synthesis
RNA= single strand of DNA with slight differences mRNA=messenger RNA Ribosomes are proteins that act as catalysts for translation of mRNA into amino acids 20 kinds of Amino acids make up proteins the way the 26 letters of the alphabet make up an almost infinite # of words Poly…
Process of protein synthesis
Part of DNA strand unwinds/splits •Gene serves as a template •A copy is made (mRNA) “transcription”-in the nucleus •The mRNA leaves the nucleus •In the Endoplasmic Reticulum (ER), ribosomes (catalysts) transform the mRNA into amino acids “translation” •Amino acids (20 in humans) make…
Allele
: variation of a gene/matching copy of a gene Alleles are not always expressed. Can be dominant or recessive
orbitofrontal cortex inhibition
during creativity-fMRI study of freestyle rappers, inhibition of the OFC when they enter “flow state”, OFC(In pre-frontal cortex) involvement in self-consciousness, Psychedelics
Huntington’s disease
Symptoms most often start mid-life, eventually an early death. Changes to personality, total loss of normal behavioral, emotional, and intellectual functioning •Genetic disorder •Buildup of abnormal type of protein called huntingtin*** •Development, memory •Cell death in brain •Cor…
Inflammation in the brain causes...
neuro-excitation**
Epilepsy
•The most common neurological disorder (1 in 20 people**(not necessarily have epilepsy) will have a seizure at some point) •Abnormal electrical activity, which can spread in the brain to initiate a seizure (over-excitation)** •Excitotoxicity**, Glutamate(main excitatory protein in brain…
Treatments for epilepsy
• typically inhibitory drugs such as benzodiazepines (gaba simulating)or barbituates(gaba simulating), “anticonvulsants”, cannabinoids(anti-inflammatory, inhibitory in a different way than gaba simulating drugs) ?
Electrical current applied to a dissected nerve...
= muscle contraction (electrical stimulation)
Electricity
•Electricity is the flow of electrons from a body that contains a higher charge (more electrons) to a body that contains a lower charge (fewer electrons) • •More electrons = more negative • •This flow of electrons is capable of doing work***
Microelectrodes and neural activity
•Touching neurons with the tip of a charged electrode can cause a current flow through a neuron **(electrons) •Stimulation of the nucleus accumbens, amygdala •Electrodes can be used to measure cellular or structural activity** •Electrode is not be charged •“electrophysiology”** resear…
Electrophysiology
: very precise method of measuring individual neuron activity
Two important influences for electrical activity in neurons
•Concentration gradient/diffusion •Molecules passively diffuse until equilibrium is reached OR •Electrical/voltage gradient •Like charges repel, flow down electrical gradient until electrical equilibrium is reached •Each ion behaves based on it’s own concentration, and the collective…
A neuron at rest is like a battery
•The separation of charges takes energy •Charge is relative* to the inside of a neuron and outside-compare the two together •Neuron is more negative inside than outside** (-70mV typically, -40 to -90mV) •This provides the “potential” for activity** •This potential gives rise to the “f…
The neuron at rest Aka “resting potential
Outside the neuron •Very few negatively charged proteins (A-) •Low amount of potassium (K+) •High amount of sodium (Na+) •High amount of chloride (Cl-) Inside the neuron •Lots of negatively charged proteins (A-) •High amount of potassium (K+)-ion channels are open for it •Low amoun…
Driving forces during resting potential
•K+: moderate/mild chemical force to leave the neuron •Chem pressure to leave due to concentration of K+ inside neuron •Electrical pressure to enter •These pressures are opposing!! •Na+: strong chemical and electrical force to enter the neuron (chem and electrical) •Cl-: very weak ch…
Ion channels and pumps contributing to the resting potential-three points
•1.Leaky K+ channel (and Cl-), 2.gated Na+ channel, •3.Sodium/potassium pump: 3 Na+ out/2 K+ in
•Localized to the part of the neuron signaled. Where?
Anywhere its getting signals from another neuron****
Graded potentials
•Excitatory and Inhibitory effects of signaling from other neurons •Result in Minor alterations in membrane potential of neuron, transient •Depolarization(less negative) and Hyperpolarization(more negative)
Graded potentials cont.
The dendrites of neurons are signaled by the axon terminals of other neurons. This signal can be excitatory or inhibitory. Signal is typically a neurotransmitter. Excitatory signals make the inside of the neuron less negative “Depolarization” due to influx of positive ions—Na+is the ion m…
•Excitatory post-synaptic potential (EPSP)
•The result of an excitatory neurotransmitter signaling the post-synaptic neuron •Depolarization (inside less negative than usual) •Example: Glutamate (excitatory neurotransmitter)
•Inhibitory post-synaptic potential (IPSP)
•The result of an inhibitory neurotransmitter signaling the post-synaptic neuron •Hyperpolarization (inside more negative than usual) •Example: GABA (inhibitory neurotransmitter)
The Action Potential
žSmall amount of stimulation results in localized, graded potentials žAction potential refers to an electrical event in neurons that travels down the axon and it releases neurotransmitters** •lasts about 1 millisecond •Neuron can have many action potentials in a small amount of time •…
The Action Potential cont.
žLarge, rapid influx of Na+(driving force of an action potential**), resulting in depolarization žThen, K+ channels open, K+ rushes out, repolarizes the neuronal membrane* •to the point of hyperpolarizaton (more neg than usual -70mV, briefly) ** This electrical pattern depends on the o…
Relative Refractory
-red part, less likely to fire another action potential , requires more stimulation than usual
Absolute Refractory period
: neuron cannot fire another action potential, Green and Yellow parts
•Mechanisms contributing to the absolute refractory period are complicated, but include
• 1) Na+ channels already being open as part depolarizing way of another AP, • 2) NA+ channels closing, voltage gated • 3) K+ channels being open, repolarizes
absolute refractory period
, in which a neuron cannot generate another AP.
Rate law
-size of action potential is always the same; - only rate varies with stimulus intensity.
Absolute refractory period-
another AP cannot be generated
Relatively refractory-
can generate AP but takes more stimulation
-Voltage gated Na+ and K+ channels
Na+ into neuron depolarization. Na+ channel closes during repolarization. K+ is out during repolarization and hyperpolarization. Not sure when the K+ channels close.
Voltage-Sensitive Ion Channels
•AKA: voltage-gated ion channels • •Open due to a specific change in the membrane potential of a neuron (“threshold potential, -50mV) • •Location/channels of importance: –Voltage sensitive Na+ and K+ channels: axon hillock and along the axon –Voltage sensitive Ca++ channels: axon te…
Myelin
–Produced by oligodendroglia in the CNS and Schwann cells in the PNS –Speeds up neural impulse –*Most neurons are myelinated –Myelinated axons make up white matter in brain and spinal cord –Rem that the brain is mostly fat
•Node of Ranvier
–Part of an axon that is not covered by myelin –Tiny gaps in the myelin sheath –Enables saltatory conduction
Saltatory Conduction
AP flows down axon, regenerating between myelinated sections, based on presence of voltage-gated Na+ and K+ channels AP regenerated at the nodes of ranvier Unmyelinated nuerons have the same Na+ and K+ mechanism, but it’s not as efficient because the signal cant just skate by the my…
Multiple Sclerosis
•Disease state involving deterioration of myelin sheaths on axons in brain, optic nerves, spinal cord. “Autoimmune”•Different than dietary Omega-3 deficiency•Frequent/occasional flare-ups of symptoms and/or worsening over time Symptoms: Vary depending on the location of demyelination. …
Oxidative stress and inflammation with MS
Transmission of information is disrupted as well as slowed due to myelination damage -Axons are eventually damaged, neurons can die off -Treatment strategies are anti-inflammatory** - Often cortisol based
Cannabinoids: treatment for MS
. bind at CB2 receptors on immune cells and decrease the damaging over-activity of the immune cells -This results in decreasing inflammation and oxidative stress -Symptom relief is reported by many -Medical marijuana is already legal, who cares? (many!) -CBD: type of cannabinoid non…
Fish oil treatment for MS
: likely this repairs myelin, but is also anti-inflammatory (omega 3s for everything!) Fish oil: salmon, mackerel, sardines **Decreased inflammation and oxidative stress levels** Cytokines: specific inflammatory molecule being studied
Electrical Synapses
(few) contain “gap junctions” which allow for ions to flow from the presynaptic neuron to the postsynaptic neuron Connect: neuron to neuron, Glia to neuron **Allows: Ions (electrical communication), glucose(makes energy), oxygen(energy), amino acids(make neurotransmitters)
Presynaptic vs. Postsynaptic synaptic vesicles
-contain neurotransmitters postsynaptic membrane-receptors for neurotransmitters
any part of neurons that touch can form a synapse
**based on the ability of neurotransmitters to be in flux
4 general steps of neurotransmission
•Synthesis and Storage: •Release: typically in response to an action potential in presynaptic neuron. •Binding: neurotransmitter binds at receptor on target tissue (usually on the postsynaptic neuron membrane. But usually don’t go into the postsynaptic neuron). Specific receptors that r…
•Synthesis and Storage
: in nucleus and/or presynaptic terminal. In vesicles, synthesized in nucleus or shipped out and the synthesized.
•Release:
typically in response to an action potential in presynaptic neuron.
•Binding:
neurotransmitter binds at receptor on target tissue (usually on the postsynaptic neuron membrane. But usually don’t go into the postsynaptic neuron). Specific receptors that recognize certain ones.
•Deactivation:
the neurotransmitter is removed from the synapse so it does not signal forever.
Step 1: Synthesis and Storage
•Synthesized in the Axon Terminal –Building blocks from food are pumped into cell via transporters: protein molecules embedded within the cell membrane – •Synthesized in the Cell Body –According to instructions contained in the DNA –Transported on microtubules to axon terminal • •S…
Step 2: Neurotransmitter Release
•At the terminal, the action potential opens voltage-sensitive calcium (Ca2+) channels • •Ca2+ enters the terminal and binds to the protein calmodulin forming a complex • •Complex causes some vesicles to empty their contents into the synapse, and others to get ready to empty their con…
Step 3: Receptor-Site Activation
•After being released, the neurotransmitter diffuses across the synaptic cleft to activate receptors on the postsynaptic membrane-chemical attraction • •Neurotransmitter Receptors –Protein embedded in the membrane of a cell that has a binding site for a specific neurotransmitter
Effects of the neurotransmitter…(depend on the receptor)
Ionotropic-, metabotropic-causes cascade of chemical events, autoreceptor-presynaptic terminal
Step 4: Deactivation of the Neurotransmitter
Accomplished in at Least Four Ways 1. Diffusion away from synaptic cleft 2. Degradation by enzymes in the synaptic cleft 3. Reuptake into the presynaptic neuron for subsequent reuse 4. Taken up by neighboring glial cells e.g. astrocytes(mediate between neurons and blood brain barrie…
Ionotropic receptor:
-excitatory -inhibitory Open and closes ion channels Affect membrane potential
Metabotropic receptor:
-excitatory -inhibitory -Actions based on “second messenger” systems** -“G-Protein” coupled -Can affect ion channels -Can affect gene transcription
•Excitatory–Ionotropic:
allow positive ions to flow into neuron •Na+, Ca++ •Depolarizing effect on neuron/membrane
–Metabotropic: •Excitatory
•Stimulate activity of nucleus (gene transcription), second messenger systems (chemical cascades) •Can interact with ion channels (effect would be excitatory) - increase depolarizing influence or inhibit hyperpolarizing influence)
•Inhibitory –Ionotropic
: allow negative ions to flow into neuron •Cl- •hyperpolarizing effect on neuron/membrane
–Metabotropic: •Inhibitory
•inhibit activity of nucleus (gene transcription), second messenger systems (chemical cascades) •Can interact with ion channels (effect would be inhibitory) - increase hyperpolarizing influence or inhibit depolarizing influence)
Metabotropic receptors:
- slower to have effects - can indirectly affect ion channels - initiate second messenger systems (cascades of activity) - increase/decrease activity in nucleus - ultimately affecting gene transcription, protein - synthesis, ion channel production, NT receptor …
•Agonists:
Drugs that increase the 1) release, 2) availability of, 3) actions of, or 4) mimic (by binding at the receptor) a specific neurotransmitter.
•Antagonists:
Drugs that decrease the release, availability or, actions of, or block the receptor of a specific neurotransmitter.
Upregulation
increased receptor expression, sensitivity to binding, downstream actions –Overall effect is to increase activity of that receptor and NT system –Sensitization(more rare) or response to deficiency of the NT
•Downregulation:
decreased receptor expression, sensitivity to binding, downstream actions –Overall effect is to decrease activity of that receptor and NT system –Desensitization (tolerance) due to overstimulation
Acetylcholine (ACh)
•Excitatory (mostly) –muscle activity, Autonomic nervous system (body) •Excitatory for muscles, except heart(inhibitory on heart) –Attention functions (brain) –Wakefulness (brain) –Memory (brain) •Agonists: Nicotine, Alzheimer’s Disease –Schizophrenia? Higher rate of cigarette smok…
Dopamine (DA)
•Mostly excitatory •motor behavior*, Parkinson’s Disease-die off,movement difficulties , L-DOPA-amino acid in diet, increase amount for Parkinson’s patients, but can lead to a tolerance. •Rewarding process, attention, wakefulness, addiction •Agonists:–Amphetamine (ADHD meds, recreation…
Serotonin (5-HT)
•Mostly excitatory –Mood regulation(anxiety-goes with depression lots of times, yet over activity of serotonin can stimulate anxiety, depression-not enough serotonin activity) –Wakefulness (tryptophan?) •Agonists: antidepressants (SSRIs, MAOIs), LSD, psilocybin, MDMA-ecstasy (dat Molly…
Norepinephrine (NE)
•Similar to Epinephrine (aka adrenaline) •Excitatory (mostly) •Stress stimulates NE release in the forebrain, which increases vigilence (arousal/awareness) •Hypervigilence (PTSD, anxiety) •Agonists: SNRIs, ADHD meds •Antagonists: ADHD meds, beta blockers, PTSD
Glutamate (Glu)
•Main excitatory NT in brain •LTP in memory •Magnesium •Hypoxia/hypoglycemia • •Agonists: D-cycloserine •Antagonists: DXM, PCP, Ketamine –GABA agonist over Glu antag
GABA
•gamma-Aminobutyric acid •Main inhibitory NT in brain •Withdrawal • •Agonists: Benzodiazepines, alcohol, barbituates •Antagonists: uncommon, reversal drugs
Endorphins
•Endogenous opioids •Pain, mood, pleasure, sleep •Runner’s high • •Agonists: pain medications, heroin •Antagonists: Naloxone •Partial agonist: Buprenorphine

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