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Why is the resting potential NEGATIVE?
- Higher Potassium INSIDE (K+)
- Higher Sodium OUTSIDE (Na+)
- 1. Selective Permiability: at rest, K+ channels are OPEN, Na+ CLOSED
- 2. Diffusion along Concentration Gradient: High to Low concentration. K+ flows OUT of cell.
- Inside becomes MORE NEGATIVE
- K+ stops flowing when outside becomes too negative
- 3. Sodium/Potassium pump restores charge
- Active transport: Na+ leaks INTO cell (Uses lots of energy)
- NOW Pumps Na+ out & K+ in
- Na+:K+ = 3:2
Neuron membrane AT REST
- SALTY BANANA CHIP:
- Higher Potassium INSIDE (K+)
- Higher Sodium OUTSIDE (Na+)
- Voltage-gated sodium channel CLOSED
- Inside NEGATIVELY charged =POLARIZED
- Neurons get signals & change state - Proportional to stimulus.
- Transient (ends when stim ends)
- Dissipates with time/space
- NEGATIVE current = Hyperpolarizing
- Larger negative response, goes back to resting.
- POSITIVE current = Depolarizing
Action Potential STEPS
(After voltage reaches threshold)
- Depolarization above threshold
- Initially graded potential
- Above threshold = Action potential
- Threshold ~ (-50)
- 1. Voltage-gated sodium channel: Opens at Threshold
- 2. Sodium rushes in, makes cell MORE POSITIVE
- 3. Stays open only .5 to 1 msec, slams shut
- 4. K+ more permiable, so K+ rushes back in & Repolarizes
- Messages sent by axons
- Nerve Impulse
- Information unit
- Always same size/shape
- More stimulus = more rapid impulses, NOT larger impulse
- DEPOLARIZATION (More +)
Undershoot Phase following Action Potential
- Occurs because most voltage-gated Potassium channels are still open
- Total Potassium of neuron is greater than when neuron is at resting state
- A protein-mediated process that expends energy to enable a molecule to cross a membrane
- Sodium-Potassium pump transports Sodium OUT of cell and Potassium IN to maintain Negative charge
- examples in the brain:
- Amino Acids
- Some Vitamins
- Some Hormones
- Axon that brings information INTO a structure.
- Every sensory neuron is an afferent TO the rest of the nervous system
- (every motor neuron is an efferent FROM the nervous system)
- Turn ON or MIMIC effects of Neurotransmitters
- ex Drugs that cause neurons to RELEASE dopamine
- ex Alcohol, benzodiazapines - INCREASE activity of GABA
- Post-Synaptic Agonist
- Ethanol binds to MANY RECEPTORS:
- AC h R(Acetylocholine)
- GABA R (main actions)
- 5-HT (Serotonin)
- NMDA R (glutamate receptors)
- Alters DA (dopamine) - Increases at receptors in the nucleus accumbens
Binds to GABA receptor (brains's main inhibitory site)
- Increases GABA activity
- ex like benzodiazepines
- Blocks activity at the Glutamate receptors (brain's main excitatory site)
- These both lead to DECREASE IN BRAIN ACTIVITY, especially in areas of the brain responsible for inhibiting risky behaviors.
- Turn OFF or BLOCK neurotransmitter effects
- ex Meloxone (for Heroin overdose)
- Stimulant that increases excitement, alertness, activity.
- Blocks reuptake of dopamine and other NTs
- Stimulates dopamine synapses in the nucleus accumbens & elsewhere by increasing the presence of dopamine in the presynaptic terminal.
- Similar effects on serotonin & norepinephrine transporters
- Increase accumulation of dopamine in the synaptic cleft
- Part of brain associated with fear, anxiety, emotions.
- Enhances startle reflex
- Important in learning what to fear
- Ananda = "Bliss"
- Endogenous cannibinoids
- Other chemical: (2-AG)
- Brain Chemical that binds to cannabinoid receptors
- Post-synaptic neuron responds to stimulation by releasing it, to travel back to the presynaptic terminal, where it inhibits further release of neurotransmitter.
- Receptors on PREsynaptic neuron. 2-AG tells cell that the POST cell got the message, don't need to send it again
- (THC or plant-derived cannibinoids attach to these same receptors & do the same thing)
- Anterior: Front/ In front of
- Posterior: Back/ Behind
- Transporters: Move neurotransmitters (NT) in and out of cell, bring back into PRE-synaptic cell so action stopped & recycled through use
- Anterograde Transporters: occurring or performed in the normal or forward direction of conduction or flow
- Post-Synaptic Agonist
- Activates D2 (dopamine2) receptor – it binds & acts like DA
- Heroin stimulates mu (opioid receptros) R for analgesia, results in euphoria
- It has been tried for a variety of uses including psychiatric treatment of homosexuality in the early 20th century, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Parkinson's disease. It is a potent emetic (i.e., it induces vomiting)
- PROGRAMMED Cell death.
- Period where neurons die
- ex Spinal Motorneurons
- Cell in spinal chord → muscles in chicks & humans count how many motorneurons in each development stage
- Chicks: MANY
- in incubation, goes way down after hatching (20k -12k)
- Humans: 175k at birth to 125k at 30 weeks
- Make lots of motorneurons – live when they make it to target
- Other chemicals which are secreted by other neurons/types of cells.
- They keep neurons alive
- ONE type of glial cell
- Star shaped (Astro - star)
- Holds blood vessels in place & structures
- Wrap around PREsynaptic terminals. Take up ions realeased by axons, releasing them back to axons
- Help synchronize activity of the axon, enabling them to send messages in WAVES
- Also remove waste material created when neurons die
Autonomic Nervous System
- Part of the Peripheral Nervous System (PNS) that controls the heart, intestines, & other organs
- Includes Sympathetic nervous system (expends energy) and Parasympathetic nervous system (conserves energy)
- Some cell bodies in brain & spinal cord & some clusters along sides of spinal cord
- On PRE-synaptic cell
- (receptors for yourself)
- Gives cell feedback
- NT released – also feeds back on it – tells it to WAIT & not fire
- (Negative feedback)
- Long structure coming out.
- Neuron's information sender.
- SENDS NEURAL IMPULSE FOR AP (action
- potential/nerve impulse)
- Firing/info goes one direction, while chemicals go back & forth throughout the cell, JUST NOT INFO OR ELECTRICAL FIRING but BOTH
- "Small hill”.
- Structure between axon & cell body (soma)
- WHERE AP STARTS
- aka terminal bouton, button.
- Ends of axons
- After AP comes down, it releases its own chemical/neurotransmitter that affects the next neuron (dendrites of another neuron)
- Neuron 1 CLOSE to neuron 2. Not connected.
(Brain -> Forebrain -> Cerebral Hemispheres -> Basal Ganglia)
- A group of subcortical forebrain structures lateral to the thalamus
- In Central Nervous System (CNS)
- Tail-like nucleus = Caudate
- Involved in motor control/function
- Parkinstons, Huntington's disease affects
- Learning and remembering HOW to do something, for attention, language, planning & other cognitive functions.
- Subdivisions exchange info w/other parts of cerebral cortex
- The concept that the entering dorsal roots (axon bundles) carry sensory information (AFFERENT neurons TO CNS)
- Exiting ventral roots carry motor information. (EFFERENT neurons FROM CNS)
- Axons to and from the skin & muscles are the PNS (peripheral nervous system)
- Anti-anxiety drugs
- ex Diazepam/ Valium, chlordiazepoxide/ Librium, alprazolam/ Xanax.
- They bind to the GABA A receptor, which includes a site that binds to GABA & sites that modify the sensitivity of the GABA site
How do Benzodiazapines work?
- At center of GABA A receptor is a chloride channel.
- When open, it permits Cl- to cross the membrane into the neuron, hyperpolarizing the cell
- Around the chloride channel are 4 units, containing sites sensitive to GABA
- Benzos bind to additional sites on 3 / 4 of those units
- When they bind, they TWIST the receptor the GABA binds more easily
- Effects seen in amygdala, hypothalamus, midbrain & other areas
Blood brain barrier (BBB)
- Mechanism that excludes most chemicals from the brain
- Good: Poisons/toxins less likely to get through
- Bad: Presents challenge for ppl to get drugs to brain (ex dopamine for Parkinsons, cant get through barrier, cancer drugs).
How the Blood Brain Barrier works
- Barrier depends on endothelial cells that form walls of the capillaries
- Body: Endothelial cells have small gaps
- Brain: Endothelial cells TIGHT so few things able to pass
What passes through Blood Brain Barrier?
- 1.Small uncharged molecules - oxygen & carbon dioxide - pass
- through. Water passes through special protein channels in wall of
- endothelial cells
- 2.Molecules that dissolve the fats of the membrane cross. ex vit A & D and antidepressants & psychiatric drugs
- 3. Active transport: Protein-mediated process expands energy to pump chemicals from BLOOD INTO BRAIN. Pumps glucose & some amino acids
- The portion of the brain associated with LANGUAGE PRODUCTION
- Broca's Aphasia = Deficit of language production
- Frontal Lobe
- Left Hemisphere
- Maps of cortical areas
- Areas 1, 2 and 3 are the primary somatosensory cortex
- Area 4 is the primary motor cortex
- Area 17 is the primary visual cortex
- Areas 41 and 42 correspond closely to primary auditory cortex.
- Among most abundant receptors in mammalian brain (scarce in the medulla, which controls breathing & heartbeat. This is why pot doesn't kill people)
- Two brain chemicals that bind: Anandamide (AN) & 2-AG
- They are located on PREsynaptic neuron
- When certain neurons are depolarized, they release AN or 2-AG as RETROGRADE transmitters that travel back to incoming axons & inhibit further release of GLUTAMATE or GABA
- Normal: AP comes down, NT released , then NT interacts w/ receptors – metabotrophic or ionotrophic (on POST-synaptic cell)
- THEN: marijuana like compounds are made & released from POST cell, go BACKAWARDS, interact w/receptor on PRE cell.
- Changes way OTHER synaptic process works
- The chemicals in marijuana decrease both excitatory & inhibitory messages from neurons
Cannabinoid Effects: What makes some of them pleasant?
- Cannabinoids increase dopamine in the nucleus accumbens INDIRECTLY.
- They inhibit GABA release in the ventral tegmental area of the midbrain; a major source of axons that release dopamine in the NA. By inhibiting GABA there, cannabinoids decrease inhibition (INCREASE ACTIVITY) of the neurons that release dopamine in the NA.
- Caudal = Posterior/ Tail plane/ farther from the head. Of, at, or near the tail or the posterior end of the body. In the human
- case, toward the bottom of the feet (also the "tail" of the spinal cord,
- and body)
- Rostral = Front of the face. Situated toward the oral or nasal region, or in the case of the brain, toward the tip of the frontal lobe.
- Cannabinoid Receptor type 1
- Located in Central & Peripheral Nervous Systems (CNS) & (PNS)
- Located on PRE-SYNAPTIC neuron
- Activated by AN & 2-AG, and THC & synthetic forms
- G-Protein coupled receptor (large protein family of receptors that sense molecules outside the cell and activate inside signal transduction pathways then cellular responses. They are called seven-transmembrane receptors because they pass through the cell membrane seven times.)
Cell Adhesion Molecules (CAMs)
- Used for migration
- Neurons inch along using these, to move along pathways
- Sturcture containing the nucleus, robosomes,& mitochondria
- Metabolic work of the neuron
- Covered w/synapses on its surface, like the dendrites
- Glial cells important for this – support structures – non neurons neurons inch along these using cell adhesion molecules, move along pathways
- Problems along result in conditions: Kallmann's syndrome
- Found: women infertile Couldnt smell
- Why? Cells couldnt migrate
- Cells born in olfactory, migrate to hypothalamus, connect w/ reproductive system
- Found: Orphaned reproductive cells in wrong place
Central Nervous System (CNS)
- Brain and spinal cord
- Cerebral cortex & areas – BILLIONS of neurons (12-15 billion)
- Cerebellum (the little brain) (70 billion neurons)
- Spinal cord – 1 billion neurons
- aka "The Little Brain"
- Large hindbrain structure w/many deep folds
- Contributes to control of movement
- Important for balance & coordination
- Controls shifting attention b/w auditory & visual stimuli, sensory timing
- Brain -> Forebrain - Cerebral Hemispheres
- Right Hemisphere, Left Hemisphere
- Include the 4 lobes
- Layers of cells on outer surface of the cerbral hemisphere of the forebrain
- Contains the 4 lobes
- Cells are gray matter
- Axons extending INWARD are white matter
Cerebrospinal Fluid (CSF)
- A clear fluid similar to blood plasma produced by choroid plexus (cells) in the brain ventricles (4 fluid-filled cavities in the brain)
- Produced by glial cells
- Cushions the brain (less susceptible to injury)
- Releases fluids & toxins
How the Cerebrospinal Fluid (CSF) works
- CSF fills ventricles
- FLows from lateral ventricles to third & forth ventricles
- From fourth ventricle, some flows into central canal of spinal cord
- More goes into narrow spaces b/w brain & meninges (membranes that surround brain & spinal cord. Swelling of these responsible for headaches/migraines. Have pain receptors)
- Here, the blood reabsorbs the CSF
Opening to allow IONS to move back/forth
Voltage-gated Sodium Channel
- 10+ versions
- Can have something wrong with 1 of them; if error, the protein for this wouldn't function. Mutation leads to kids having
- epilepsy since channel for neuron isn't working
Ligand-gated Chloride Channel
Open/close depends on whether something binds to it
- Part of Synaptogenesis (Neurons' need to connect)
- Chemical Signal to attract correct address. Chemical beacons tell cells where to go.
- Negatively charged
- Mainly outside cell
- If INSIDE, cell will become more NEGATIVE (IPSP)
- When membrane at rest, concentration & electrical gradient balance, opening chloride channels little effect, but have NET FLOW when membrane's polarization changes.
- Difference in distribution of ions across neuron's membrane
- High to low concentration ALWAYS
- Since SODIUM more concentrated OUTSIDE, they are more likely ENTER the cell. BUT since sodium channels closed, only Sodium gets out through Sodium-Potassium pump
- plane cuts top to bottom & left to right (vertical)
- - Guillotine
- - Crown, from ear to ear
- plane plane cuts front to back & top to bottom (vertical)
- - Along nose
- plane cuts from front to back & side to side (horizontal)
- Bundle of axons that connect the 2 hemipheres of the cerebral cortex
- Allow 2 sides to communicate
- Cortex arranged in layers throughout cortex. Many connection in columns. One neuron synapses along many other connections (1,000 to 1,000,000)
- a group of neurons in the cortex of the brain which can be successively penetrated by a probe inserted perpendicularly to the cortical surface, and which have nearly identical receptive fields
- The different cortical layers each contain a characteristic distribution of neuronal cell types and connections with other cortical and subcortical regions.
- One of the clearest examples of cortical layering s the Stria of Gennari in the primary visual cortex. This is a band of whiter tissue that can be observed with the naked eye.
- Nerves that control sensations from the head, muscle movements in the head, & much of the parasympathetic output to the organs
- 12 Total
- Some overlap
- 9 & 10 processing taste
- Tells you how much to eat
- Bring infointo brainstem
- Some of the cranial nerves include BOTH sensory & motor components
Branches from neuron that RECEIVE signals from other neurons
- Short outgrowths that increase the surface area available for synapses
- More surface area = More information it can receive
Less negative = Positive. More positive leads to action potential
View that "biology" means something is determined. But BIOLOGY IS NOT DETERMINISM. (It's not necessarily fixed)
- Cells different shapes, sizes,
- Cells different TYPES, functions
- Epigenesis = Genetic programming. Some genes expressed - turned on or off.
- ex Cells in spinal cord become motor neurons
- Remove notochrod early - no motor neurons
- Induction = Influenced by notochord
- Take ANOTHER and place next to, more cells will become motorneurons that werent supposed to
- Sonic Hedgehog = Chemical inductive stimulus
- The tendency of molecules to go from High concentrated state to Low concentrated state.
- Movement by concentration gradient.
- Related to REWARD
- Used to treat Parkinsons
- Monoamine (1 amino acid)
- Localized. Much less diffused, found in small regions of the brain.
- All dopamine is the same, but the receptors are different (5 FOUND) (D1-D5)
- allows for flexibility
Dorsal (sensory) root ganglion
- Clusters of sensory neurons outside the spinal cord
- Relationship b/w amount of dose and amount of effect.
- Usually an "S" shape, b/c reaches a ceiling
Down-regulation of receptors
- DESENSITIZATION OF RECEPTORS
- One of the reasons for withdrawal symptoms
- Cell decreases quantity of cellular component
- Most receptor agonists downregulate their respective receptor