Exam I Flashcards
Who used the silver stain to study the nervous system, developed the neuron doctrine, and is known as a pioneer in neurobiology?
Ramon y Cajal
Neurons are the elementary signaling elements of the nervous system
Neuron doctrine
The oldest part of the brain, beginning where the spinal cord swells and enters the skull.
The brainstem
What is the brain stem responsible for?
Automatic survival functions
What are the three major regions of the brain stem?
Medulla oblongata, pons, and midbrain
Which parts of the brain stem serve important functions in motor movement, particularly movements of the eye, and auditory/visual processing?
Midbrain and pons
-functions are involuntary or done without thought (autonomic nervous system)
- we would not be able to live without this
- helps regulate blood pressure and breathing
- brain surgeons are extremely cautious around this area
Medulla oblongata
-part of the hindbrain (ancient rear part of the brain)
-acts as a bridge and has nerve fibers connecting the cerebellum to the medulla
-main function is to carry relay signals from the cerebrum down to the cerebellum and medulla
-takes sensory signals up to the thalamus
-mostly involved in motor movement
Pons
Consists of the medulla oblongata, the pons and the cerebellum, which control respiration and movement among other things
The hind brain
-brains sensory switchboard located on top of the brain stem
-directs messages to the sensory areas in the cortex and transmits replies to the cerebellum and medulla
- relays all senses to the cerebral cortex, except olfactory senses
-consists of white matter
Thalamus
-nerve network in the brainstem that plays an important role in controlling arousal
-“traffic cops of the brain”
-thought to be associated with narcolepsy
Reticular formation
What happens when you yawn?
Jaw muscles contract, stimulating the reticular formation and encourage wakefulness
-the “little brain” attached to the rear of the brainstem
-helps coordinate voluntary movement and balance
Cerebellum
Disease that is characterized by muscle weakness and ataxia (loss of balance and coordination)
Primarily targets the cerebellum and does not involve parts of the brain involved with thinking.
Hereditary disease
Friedreichs ataxia
-regulates levels of iron inside mitochondria
- acts like a storage depot for iron, releasing it only when it is needed
Frataxin protein
What is the cause of FA?
-when frataxin is missing or defective, free iron accumulates in the mitochondria and oxidative stress damages the mitochondria. This leads to a death of the cerebellar neurons that control movement
The buildup of harmful oxygen based free radicals
Oxidative stress
Neurons are post mitotic
Meaning we are born with a set of neurons and do not make more.
What is a typical treatment for FA?
An iron kelater (binds free iron)
The wrinkled gray matter covering the cerebral hemispheres
Cerebral cortex
Lobe involved in judgement and planning future action
Frontal
Lobe involved with somatic sensations
Parietal
Lobe that’s primary function is processing visual information
The occipital lobe
Primary function is involved in hearing and memory
Temporal lobe
What percent of neurons are in the cortex?
80%
What is the cortex plus the white matter?
Cerebrum
Where the cell bodies are
Gray matter
Where the axons are
White matter
Each hemisphere controls sensory and motor processes on the opposite side of the body
Contralateral
Are the hemispheres symmetrical in structure and function?
No
The left and right hemispheres communicate with each other by a mass of connections called the..
Corpus callosum
Impairment of language, usually caused by left hemisphere damage either to Broca’s area or wernickes area
Aphasia
What would damage to Broca’s area do?
Impair speech
What would damage to wernickes are do?
Impair understanding
Receives written words as visual stimulation
Visual cortex
Transforms visual representations into an auditory code
Angular gyrus
Interprets auditory code
Wernickes area
Controls speech muscles via the motor cortex
Broca’s area
Word pronunciation
Motor cortex
Disease where the fibers connecting Broca’s and wernickes area are damaged
Conduction aphasia
An amplified recording of the electrical waves sweeping across the brains surface
Electroencephalogram (EEG)
Visual display of brain activity that detects a radioactive form of glucose while the brain performs a given task
Positron emission tomography (PET) scan
Uses magnetic fields and radio waves to produce computer generated images that distinguish among different types of brain tissue
MRI (magnetic resonance imaging)
Magnetizes certain molecules in the brain and makes them resonate, allowing us to measure and map brain activity in real time
fMRI (functional MRI)
Phagocytes that are mobilized after injury, infection, or disease
Microglia
What are the three types of microglia?
Oligodendrocytes, Schwann cells, astrocytes
What microglia are found in the CNS
astrocytes and oligodendrocytes
What microglia are found in the peripheral nervous system
Schwann cells
What microglia form myelin to insulate nerve cell axons
Oligos and Schwann cells
Most numerous type of microglia in the CNS
Characterized by star like shape and the end-feet that form the BBB
Astrocytes
What microglia help maintain the right potassium ion concentration by buffering excess k+ in the extracellular space
Astrocytes
-formed by tight junctions made by the end feet of astrocytes wrapping around blood vessels
Blood brain barrier
What are the three main functions of the BBB
- protects brain from foreign substances in the blood (charged and polar things cannot cross)
- protects brain from hormones and neurotransmitters in the rest of the body
- maintains a constant environment for the brain
What are the four defined regions of a neuron?
- Cell body (soma)
- Dendrites (input region)
- Axon (output region)
- Presynaptic terminal
Part of the neuron that is the metabolic center of the cell
Cell body
-shorter in length than axons
-tend to branch out in a tree like fashion
-main apparatus for receiving incoming signals
Dendrites
-long and tubular in nature
-always extend away from the soma
-main conducting unit
Axon
Near the end of the neuron the axon divides into fine branches that form the…
Presynaptic terminal
Small protruding membranous organelles found on the dendritic processes of neurons where the majority of excitatory synaptic signaling occurs in the brain
Dendritic spines
Someone who is born with less dendritic spines may have what diseases
Rubella, fetal alcohol syndrome, Down syndrome
What nerve cell is responsible for transmitting a signal
Presynaptic cell
What nerve cell is responsible for receiving the signal
Post synaptic cell
The Presynaptic cell transmits signals from the swollen ends of its axon branches called
Presynaptic terminals
Rapid, transient, all or none nerve impulses
Action potential
Action potentials typically have an amplitude of ___ and a duration of ___
100 mV and 1 msc
What is the range for the distance that and action potential can convey an electrical signal
0.1 mm to 3 meters
Action potentials are initiated at a specialized region called the…
Axon hillock
The size and the shape ____ as it travels down the axon
Remains the same
How is information conveyed by APs interpreted and analyzed by the brain if they all have the same shape and size
The frequency of the AP varies
To increase the speed by which action potentials are conducted, axons are wrapped in a fatty insulated sheath called
Myelin
The knee jerk response is ___, meaning it does not have to have any influence from the brain
Self contained
The knee jerk response is an example of a ____ system where you have a direct connection between sensory and motor neurons
Monosynaptic reflex
Explain the steps of the knee jerk response
- Tapping the knee pulls on the tendon of one of the quadriceps
- The muscle stretches and is then sensed by afferent neurons
- In the spinal cord sensory neurons act directly on extensor motor neurons that contract the quadriceps and the muscle is stretched
- At the same time the sensory neurons act indirectly via an inhibitor interneuron that inhibits the flexor motor neurons
Neurons entering the spinal cord
Afferent
Neurons exiting the spinal cord
Efferent
What are the four different sites that signals are generated at in a neuron?
- A local input signal
- A trigger signal
- A long range signal
- An output signal
A neuron that has the cell body in the middle
Bipolar neuron
At rest all cells maintain a difference in
Electrical potential
What is the resting membrane potential
-65 mV
Two factors contributing to the differential in membrane potential:
- Unequal distribution of charged ions on either side of the membrane
- The selective permeability to potassium (k+)
At rest, these channels are open and potassium ions tend to leak out, Leaving behind negative charges making the inside of the membrane
more negative than the outside
- reflex that keeps knees from buckling when you stand up
-causes muscle contraction in response to increased muscle length
-initiated by stretched muscle spindles
-contraction of stretched muscle and inhibition of its antagonist
Stretch reflex
The input component produces
Graded local signals
Ionic current disturbs the testing membrane potential, driving the potential to a new level called the
Receptor potential
A signal that spreads passively along the axon
A local signal
The receptor potential spreads passively to the ____ where it triggers an action potential
Trigger zone
An action potential is only generated if
The input signal is greater than a certain threshold
After the threshold is met only the ____ in which the APs are generated changes
Frequency
-Results in severe impairment of cognitive function in children
-children have two abnormal copies of the gene that codes for phenylalanine hydroxylase
-therefore they build up high blood levels of phenylalanine
-autosomal recessive
Phenylketonuria
What does phenylalanine hydroxylase do?
Converts phenylalanine to tyrosine
PKU is an example in which ____ can modify the phenotype
Environmental factors
Leads to the production of a toxic metabolite that interferes with the normal maturation of the brain
High blood levels of PHE
What treatment is easy and effective for PKU
Restrict protein intake
Who proposed that individuals with high mental skills were more likely to have children who were very smart and introduced the idea of twin studies
Francis Galton (1869)
What is the single gene found on chromosome 6 that influences eating behavior?
The ob gene
What does the ob gene code for?
A protein called leptin, that is selectively expressed in adipose tissue and released in the blood stream
In a normal mouse what happens when adipose tissue decreases
Leptin levels decrease and the animal eats more
Mice with homozygous mutations in the ob gene lack
Leptin
Where is the leptin receptor expressed at high levels?
The hypothalamus
Type of protease whose role is to chew up proteins like the leptin receptor
MMP2
What dopamine receptor gene is thought to be associated with being more promiscuous
DRD4
What does DRD4 code for
The dopamine receptor D4
What variant of DRD4 is linked to lower dopamine sensitivity
DRD4-7R
The 7R+ version does not bind dopamine as effectively, therefore people with this version need
Higher levels of dopamine to feel pleasure
What neuropeptide receptor stimulates pair bonding and parental bonding
Vasopressin
Monogamous voles show high expression (more activity) of a vasopressin receptor in an area of the brain called
Ventral palladium
One of the first complex human behavioral abnormalities to be traced to a single gene
Huntingtons disease
HD is a neurodegenerative disorder characterized by four features:
- Heritability
- Chorea
- Cognitive impairment
- Death
When does HD typically onset
Fourth to fifth decade of life
HD involves death of neurons in the
Caudate nucleus, a part of the basal ganglia involved in regulating voluntary movement
HD is ___ and the mutation is highly penetrating
Autosomal dominant
Where is the mutant gene found for HD
on chromosome 4
What is different about the mutated form of Huntington protein
A long stretch of the amino acid glutamine (positively charged)
What codon repeat causes the long stretch of glutamine for HD
CAG
Each successive generation of a family the harbors the mutant gene manifests the disease with greater severity at an earlier age
Genetic anticipation
What kind of mutation causes a poly glutamine structure
Gain-of-function
Q is
Glutamine
An Exon is
The coding section
Who discovered the HD gene in 1993?
Nancy wexler
What treatment for HD did they bring to human trials and ended up causing worsening symptoms for elderly people
Tominersen (antisense oligonucleotide)
Ions are strongly attracted to water because water molecules are
Dipolar
Water molecules interact with ions via
Electrostatic forces
Which ions interact more strongly with water
Smaller ions
Energy gained by transferring an ion from a vacuum into aqueous solution
Hydration energy
Electrostatic force is proportional to the inverse square of the distance between charges, therefore water molecules can approach closer to the center of smaller ions and the force will be larger
Coulomb’s law
Which ions can shed water molecules more easily
Larger ions
A carrier that specifically increases the permeability of membranes to potassium
The antibiotic valinomycin
Forms a relatively stable pore across the membrane through which small cations but not anions pass
Gramicidin
Which method (pores or carriers) has a higher maximum speed of ion flow
Pores
The rate of ion flow through pores depends on
The highest energy barrier
Pores act similar to enzymes, in that they
Reduce the height of the energy barrier
What do most ions do to enter a channel
Partially dehydrate and form weak bonds with chemical groups inside the pore
At high levels of substrates, ion flow through a pore
Saturates
What is one of the most important features of channels in excitable cells?
Ion specificity
Smaller ions attract water more strongly, causing them to have
A larger water shell
Which is bigger sodium or potassium
Potassium
Which is bigger including the water shell (sodium or potassium)
Sodium
What makes the sodium channel specific to sodium other than pore size
Selectivity filter
Narrow region that acts as a molecular sieve. Ion sheds it’s water molecules and forms weak chemical bonds with the polar aa lining the wall of the channel
Selectivity filter
What is more easily stabilized at the selectivity filter
Sodium
It is thought that ion channels are selective both because of
Specific chemical interactions and molecular sieving based on pore diameter.
You would expect the binding site for an ion in the aqueous pore of a cation channel that allows the ion to shed its water molecules to have
Negatively charged amino acid residues
Ohms law
I=V/R
The more open ion channels you have, the higher the…
Conductance
A glass micropipette is brought into close contact with the surface of a cell and gentle suction is applied to isolate individual channels
The patch clamp technique
What blocks sodium channels
Tetrodotoxin
The more channels involved in a patch, the more closely the patch current resembles the
Whole cell current
Ion channels exist in three different conformational states
- Closed state
- Open state
- Inactivated state (open but not conducting)
The transition of a channel between the conformational states
Gating
Neurotransmitters regulate the opening and closing of an ion pore by binding to a site on the channel protein
Ligand gated channels
What is the main ligand channel in the post synaptic membrane at the neuromuscular junction?
Nicotine ach receptor
The response of the receptor to ach can be separated into two steps:
- Ligand-receptor complex
- Conformational change of protein to an open state
What are the five polypeptide subunits of the ach receptor
Two alpha, beta, gamma, and delta
The binding surface of the ach receptor appears to be primarily on the
Alpha subunits (near the outer surface)
The ach receptor subunits have recognition sites for
Agonists, reversible antagonists and alpha-toxins
The membrane spanning regions of the receptor are
Alpha helical
The N terminal and C terminal of the ach receptor are
Extracellular
The transmembrane segments are
M1,M2,M3, long cytoplasmic loop, M4
What is the most highly conserved segment of the subunits
The transmembrane region
What is the hallmark of excitable cells
Voltage gated ion channels
Voltage gated ion channels in the closed state are opened by
Membrane depolarization
Channel responsible for the rapid membrane depolarization made from a single subunit. Voltage dependent and very fast
Sodium channels
During the inactivation state, the sodium channel is in a
Refractory period
What channels are important drug targets
Sodium channels
Binding of drugs to the sodium channel maintains the channel in
An inactivated state
Since drugs only bind to open sodium channels, their inhibitory effect is
Use and voltage dependent
What drugs act as sodium channel blockers
Anti-arrhythmias, anticonvulsants, and local anesthetic (lidocaine)
A single pass integral membrane glycoprotein composed of three separate membrane spanning regions)
Tripartite
What will always be Extracellular for cell identification
Glycoproteins
The large sub unit of sodium and calcium channels have how many homologous domains
4
Wishing each domain for sodium pumps how many membrane spanning regions are there
6
Which domain has an amphipathic structure and is thought to act as a voltage sensor
S4
The region between what two domains forms the pore for the sodium channel
S5 and S6
The region between S5 and S6 is known as
The P domain
Much of what we know about potassium channels comes from the study of
Shaker flys
What is characteristic about shaker flies
Prolonged AP
The shaker gene codes for a protein that is _____ than that of other voltage gated channels
Much shorter
The shaker protein has ___ hydrophobic segments that are membrane spanning
6
Four of the membrane spanning sections in the shaker protein form a
Tetramer
Why does this channel lead to prolonged AP
Does not properly inactivate
For normal ion channel functioning what is the molecular mechanism by which ion channels inactivate
An intracellular loop acts as a blocking particle
What enzyme would cleave the ball and chain
Pronase
Applying positive charge into a system for artificial polarization
Step up
The ball on the ball and chain inhibitor is likely a
Negatively charged protein
Channel formed by two homodimers, voltage independent and contributes to the resting potential
Leak potassium channels
Work that have opposite polarities
Negative work
Work that has the same polarities
Positive work
What is a measure of the work required to separate ions
Voltage
The greater the concentration gradient, the ___ the voltage
Larger
The resulting movement of charges between areas of potential difference is
- defined as the net movement of positive charge per unit time
Current flow
Any object through which electrical charges can flow is a
Conductor
Current (I) equation
Current= potential difference x conductance
Equation for conductance (g)
Conductivity x (area/length)
If the length of an axon increases or the diameter decreases the conductance
Is reduced
The reciprocal of conductance and is a measure of the resistance provided by an object to flow
Electrical resistance
Insulators have ___ conductivity
Low
The more open channels you have, the ___ the resistance
Lower
Consists of two conducting plates separated by an insulating layer (ability to store charges of opposite signs)
Capacitor
Normally are open and are not influenced by extrinsic factors such as potential across the membrane (important for maintaining the resting membrane potential)
Resting channels
Closed when the membrane is at rest and can be regulated by three factors:
1. Changes in membrane potential
2. Ligand binding
3. Membrane stretch
Gated channels
Positive charge on the outside, negative charge on the inside (-60- -70 mV)
Resting membrane potential
A reduction of charge separation leading to a less negative membrane potential
Depolarization
An increase in charge separation leading to a more negative membrane potential is
Hyper-polarization
__ is more concentrated inside the cell and ___ is more concentrated outside the cell at rest
K+ and Na+
When the electric force driving potassium into the cell is equal and opposite to the chemical force driving potassium out of the cell
Ek
For most cells at rest, the membrane is most permeable to
Potassium
When Vm is closer to Ek (-75 mV) it means
The membrane is most permeable to potassium at that time