Neurochemistry Flashcards
What did Roman y Cajal do?
Used the Golgi Technique that fills in some cells completely to allow to trace the entire shape of cells in our brain
What did Otto Loewi do?
Studied frog hears in vitro in 1920
Electrically stimulated 1 heart via the vagus nerve and noticed a decrease in heart rate
Transferred the liquid from first hear to the second and noticed a decrease in heart rate even through the second heart did not have stimulation
What is electrophysiology?
2 electrodes are placed
- One inside the cell
- Other is made of glass and placed into cell (intracellular)
What are voltage gated channels?
Transmembrane proteins
Amino acids twist depending on the charge of the membrane
Novocain binds and prevents Na channels opening, blocking APs
What do myelin sheaths do?
AP jumps to Nodes of Ranvier in 1mm intervals which contain Na channels
Prevents the loss of ions
Velocity of AP increases as the diameter of the sheath increases
Insulating fat material on axon found in vertebrates
Role of neurons
Receive information and transmit it to other cells
- 86 billion neurons and 85 billion glia
- 16 billion neurons in the cortex and 69 billion neurons in the cerebellum
Multipolar interneuron
Short/no axon
Integrate neural activity with one brain region and do not conduct information to other regions
Multipolar neuron
More than 2 processes
Most neurons are this type
Bipolar neuron
2 processes
Unipolar neuron
Contains 1 process extending from the cell body
What are the 4 major classes of neurons
Unipolar, Bipolar, multipolar, multipolar interneuron
How do neurons vary
- Morphology (determines its connections/plasticity)
- Function (releted to the shape)
- Transcriptone (genes expressed by cell)
What are local neurons?
Small neurons without axons
Exchange information only with close neighbours
Do not follow the all-or-none law
Incoming information has a graded potential:
- Varies in magnitude in proportion to the intensity of stimulus
- Gradually decays as it travels
Define interneuron/intrinsic neuron
Cell’s dendrites and axon are entirely contained within a single structure
Define efferent axon
Brings information away from the structure
What is a motor neuron?
Has its soma in the spinal cord
Receives excitation through its dendrites and conducts impulses along its axon to a muscle
What is a presynaptic terminal?
At the end of an axon branch releasing chemicals into synapse
What is an axon?
Thin fiber constant in diameter, only 1 per neuron but has branches
Transmit signals to other neruons, organs, muscles
AP generated at the axon hillock, presynaptic terminals at the end
What is an axon?
Thin fiber constant in diameter, only 1 per neuron but has branches
Transmit signals to other neruons, organs, muscles
Action potential is generated at the axon hillock
Presynaptic terminals at the end of an axon release chemicals
What are dendritic spines?
Short outgrowths that increase the surface area of synapse and show plasticity (change often)
- Schizophrenia may change the number of dendritic spines in the prefrontal cortex
What are dendrites
Branching fibers that get narrower near the ends, lined with synaptic receptors responsible for bringing information into the neuron
What is a sensory neuron?
Specialized at one end to be highly sensitive to a particular stimulation
What are glia?
Non-neuronal cells in CNS
Outnumber neurons in cortex
Types:
Astrocytes, Microglia, Oligodendrocytes + Schwann cells, Radial Glia
Radial glia
Guide the migration of neurons during embryotic development
Schwann cells
found in the PNS
Build myelin sheaths with with oligodendrocytes
Microglia
Part of the immune system, remove viruses and fungi from the brain
Proliferate after brain damage to remove dead/damaged neurons
Contribute to learning by removing the weakest synapses
Describe the blood-brain barrier
Endothelial cells in brain are packed so tightly that viruses and bacteria are blocked
Also keeps out chemotherapy and some therapeutic drugs
Glucose, amino acids, some hormones and vitamins enter the brain via active transport
Barrier is leaky in some areas (ex. by the hypothalamus)
Nourishment of neurons
Need Vitamin B1 to use glucose, therefore deficiency (common in alcoholism) leads to the death of neurons known as Korsakoff’s syndrome
Resting membrane potential
Membrane maintains electrical gradient (polarization) at rest
Electric potential is more negative on on the inside than the outside (-70 mV)
Resting potential is due to negative charged proteins inside the cell
Na 10x more concentrated on the outside
K 10x more concentrated on the inside
Na-K concentrations maintained by Sodium-Potassium Pump
Forces acting on ions
Sodium-Potassium pump, Na Channels, K Channels
Na channels
Closed at rest
With slight depolarization, channels open
Once threshold is reached, channels open wide and Na flows in
At AP peak, channels close and cannot be opened again for 1 ms
K Channels
Few open at rest
Once threshold is reached, channels open but K leaves slowly
Channels stay open after AP is reached and more ions exit
The cell becomes hyperpolarized and then returns back to resting membrane potential due to Sodium-Potassium pump
Membrane at rest
Sodium is pulled in due to electrical and concentration gradient
Potassium is pulled in due to electrical gradient, but pulled out due to concentration gradient
Chlorine ions mainly outside of the cell with concentration gradient equal at rest
The action potential
Means by which messages are sent by axons, electrical signal traveling down an axon
Non-decremental
Speed depends on the size of the axon and myelination
All or non law
Any depolarization that reaches the threshold will produce an action potential
All action potentials are equal in amplitude and velocity (varies in axons depending on axon width and myelination), and are independent of the stimulus
Stages of AP
- At the start, Sodium is on the outside, Potassium on the inside
- When depolarized, sodium and potassium channels open
- At first, potassium channels produces little effect
- Sodium ions rush into axon
- Positive charge flows down the axon and opens voltage-gated sodium channels at the next point
- At peak of the action potentials, sodium channels close but potassium channels are slower to change
- Potassium flows out, allowing for the membrane to reach its original depolarization
- When depolarized, sodium and potassium channels open
AP propogation
The positive charge of the sodium slightly depolarizes the adjacent area causing it to reach threshold and open its voltage-gated channels
Back propagation, Saltatory conduction
Saltatory conduction
Jumping of action potentials from node to node on myelin sheath
Back propagation
Cell bodies and dendrites passively register an electrical event at a nearby axon
The dendrite becomes more susceptible to structural changes responsible for learning
The refractory period
Cell resists production of another action potential
- Absolute refactory period +Relative refactory period
Refactory period depends on:
- Sodium channels being closed
- Potassium flowing out of the membrane at a faster rate than usual
Absolute refractory period
Happens immediatley after an action potential
Membrane cannot produce another action potential regardless of stimulation
Relative refractory period
Stronger than usual stimulus is necessary to initiate an action potential
Excitatory postsynaptic potential (EPSP)
Graded depolarization from flow of Na entering neuron
If it does not cause the cell to reach threshold, depolarization decays quickly
A quick sequence of EPSPs produces temporal summation
Spacial summation
Synaptic inputs from separate locations combine their effects on a neuron
Critical to brain functioning
Inhibitory postsynaptic potential (IPSP)
Temporary hyperpolarization of a membrane
Can regulate the timing of an activity
Synaptic input selectively opens gats for K to exit the cell or Cl to enter
Spontaneous firing rate
Periodic production of action potentials even without synaptic input
EPSPs increase the frequency of action potentials above the spontaneous rate
IPSPs decrease the frequency of action potentials below the spontaneous rate
Neurotransmitter categories
Amino acid: Glutamate, GABA, Aspartate, Glycine
Monoamines:
-Catecholamines: Dopamine, epinephrine, norepinephrine
Contain a catechol group + amine group
- Indolamines: Serotonin
Soluble gases: Nitric oxide
Modified A.A: Acetylcholine
Neuropeptides: NPY, AVP, OT
Synthesized in the cell body
Released by dendrites, cell bodies, and the side of the axon, diffuse widely
Release from dendrites primes other nearby dendrites to release the same neuropeptide
Release requires repeated stimulation, so they do not release often, but when they do, they release a lot
Chemical events @ synapse
- Neuron synthesizes chemicals that serve as neurotransmitters.
- Smaller neurotransmitters synthesized in the axon terminals and neuropeptides in the cell body
- Action potentials travel down the axon, enabling Ca to enter cell at presynaptic terminal. Ca releases neurotransmitters from the terminals into the synaptic cleft.
- Ca entering the presynaptic terminal causes exocytosis; a burst of neurotransmitter release
- Released molecules diffuse across the cleft, attach to receptors and alter the activity of the postsynaptic neuron
- Neurotransmitter molecules separate from their receptors
- Neurotransmitter molecules are either taken back to the presynaptic terminal for recycling or diffuse away
- Some postsynaptic cells send reverse messages to control further release of neurotransmitters by presynaptic cells
NT synthesis
Acetyl CoA (from metabolism) + Choline (metabolism or diet) → Acetylcholine
Phenylalanine → Tyrosine → Dopa → Dopamine → Norepinephrine → Epinephrine
Tryptophan → 5-hydroxytryptophan → Serotonin
Ionotropic receptors
When a neurotransmitter binds to an ionotropic receptor, it twists and opens its central channel to let specific ions pass Immediately opens the channel in > 1ms, short lasting Ligand gated (ligand: chemical that binds another molecule, typically a protein)
Non-NMDA: uses glutamate for Na to come in and K to go out
NMDA: uses glutamate and glycine for Ca to come in and K to go out
GABA, Glutamate, Acetylcholine
- Glutamate is most used in the brain’s excitatory ionotropic synapses
- Inhibitory ionotropic synapses use GABA
- Opens Cl gates and crosses into the cell more rapidly
Cholinergic pathway
Uses acetylcholine (generally excitatory), ionotropic
- Acetylcholine receptor: outer portion is embedded in the membrane and inner portion surrounds Na channel
- 2 acetylcholine molecules bind to the receptor at the alpha subunit and opens the channel
Metabotropic receptor
Neurotransmitter initiates a sequence of metabolic reactions that start slow but last longer than ionotropic effects (several seconds) that uses much or all of the cell and many neurotransmitters
- Neurotransmitter binds to receptor to change its shape
- The other side of the receptor is attached to a G protein (guanosine triphosphate - GTP)
- Bending the receptor detaches the G protein
- This increases the concentration of a second messenger inside the cell that communicates to areas within the cell to open or close channels
- Intracellular portion of the receptor affects other proteins (2nd messenger)
- Dopamine, norepinephrine, serotonin, glutamate, GABA
Dopaminergic receptors
Metabotropic
- Cyclic AMP is a common 2nd messenger — turns on a gene in the nucleus and can open or close ion channels
Breakdown of NT
Acetylcholinesterase (AChe)
Breaks acetylcholine → Acetate + choline
Choline can go back into the neuron to form ACh again
Monoamine oxidase (MAO)
Contained in neurons releasing serotonin, dopamine, or norepinephrine
Breaks down neurotransmitters into inactive chemicals, detaching from receptor and prevents the accumulation of harmful levels
COMT
Enzyme that breaks down any neurotransmitter not taken up by transporters
Autoreceptors
Pre synaptic receptors detect the amount of neurotransmitter released and inhibit further synthesis and release
- Provides negative feedback
Reuptake
Presynaptic neuron takes up released neurotransmitter and reuses them using transporters
Electrical synapse
Faster than chemical synapses + synchronous
Gap junction: direct contact of membrane of 1 neuron with another
Agonist
- Mimics activity of neurotransmitters, can block reuptake and prolong neurotransmitter in the synapse
- L-Dopa: agonist used for Parkinson’s
Antagonist
Blocks the activity of neurotransmitters
Mixed agonist-antagonist
Agonist for some effects and an antagonist for others or an agonist for some dosages and antagonist for others
Drug affinity vs efficacy
Affinity: Tendency for a drug to bind to a receptor
Efficacy: Tendency for a drug to activate a receptor
Contingency management
Therapy that includes rewards for remaining drug free
Opiate abuse treatment
Methadone:
Activates the same brain receptors and has the sam effects as heroin and morphine
Taken orally and gradually breaks down to avoid the “rush” and minimizes withdrawal
Buprenophrine + Levemethadyl acetate (LAAM):
Similar to methadone
LAAM has long lasting effects
Alcohol Abuse treatment
Antabuse:
Antagonizes the enzyme that metabolizes acetaldehyde
User becomes nauseated after drinking
Naloxone and naltrexone:
Blocks opiate receptors and therefore decreases the pleasure from alcohol
Hallucinogenic drugs
Many resemble serotonin and stimulate at inappropriate times or for a longer time
Nicotine
Stimulates acetyl choline receptors — nicotinic receptors
Increase dopamine release
Stimulants
Inhibit transporters for dopamine, serotonin, and norepinephrine which decreases reuptake at prolongs effects
Leads COMT to break down dopamine faster than the presynaptic cell can replace it — user feels low hours after taking the stimulant
Oligodendrocytes
In CNS
Make myelin sheaths with Schwann cells
Na-K pump
3 Sodium out, 2 Potassium in
Uses active transport
Closed when the membrane is at rest
