Bio Basis Test 1 Flashcards
I. Background A. Cell Types 1. Neurons B. Subtypes C. Relative distribution D. Functional significance
I. Background
A. Cell Types 1. Neurons
2. Glia
B. Subtypes
1. Differ based on their structure, chemistry and function
C. Relative distribution
1. 100 billion neurons (give or take 100 million)
2. 10 times as many glia as neurons
D. Functional significance
1. Neurons confer the unique functions of the nervous system
II. Cellular Structure of Neurons A. Neurons contain the same basic structures as most other cells B. Structure of animal cells 1. Cell body (soma) 2. Cellular contents 3. Nucleus 4. Ribosomes 5. Endoplasmic reticulum 5. Mitochondria 6. Golgi apparatus 7. Neuronal membrane
- Cell body (soma)
a. 20 um in diameter
b. Surrounded by a membrane that separates the inside of the cell from the outside i. 5 nm thick - Cellular contents
a. Everything within the cell membrane other than the nucleus is the considered cytoplasm - Nucleus
a. Contain the chromosomes that confer the heritable material—DNA b. Gene expression
i. DNA to Protein
ii. DNA (transcription) mRNA (translation) Protein 3. Ribosomes
a. Site where protein is made 4. Endoplasmic reticulum
a. Rough
i. Have ribosomes
b. Smooth
i. Transport completed protein to other cellular sites - Mitochondria
a. Site where metabolic functions are performed - Golgi apparatus
a. Post-translational modification of proteins - Neuronal membrane
a. Cannot understand the function of the brain without understanding the structure and function of the membrane and its associated proteins
II. Cellular Structure of Neurons C. Unique features of neurons 1. Morphological regions 2. Types of neurites 3. Axons 4. Dendrites
- Morphological regions
a. Cell body (soma or perikaryon)
b. Neurites - Types of neurites
a. Axons
b. Dendrites - Axons
a. Cell body usually gives rise to a single axon
i. Conducts nerve impulse from one neuron to the next
ii. Up to 1 meter in length
iii. Speed of the nerve impulse is a function of the diameter of the axon - Dendrites
a. Small
i. Rarely more than 2mm
b. Organized symmetrically
i. Antennae c. Dendritic tree
i. Collective term for all neurites of a given neuron
II. Cellular Structure of Neurons
D. Neural signals
1. Efferent
2. Afferent
- Efferent
a. Away from the cell body - Afferent
b. Towards the cell body
II. Cellular Structure of Neurons E. Synapse 1. Site of neurotransduction 2. Structural elements a. Axon terminal b. Presynaptic terminal c. Postsynaptic terminal d. Cleft 3. Synaptic transmission 4. Neurotransmitter 5. Receptor
E. Synapse
- Site of neurotransduction
a. Electrical to chemical signal - Structural elements
a. Axon terminal
i. Site where axon comes in contact with another neuron b. Presynaptic terminal
c. Postsynaptic terminal
i. Usually found on dendrite
d. Cleft
i. Space between the two sides of a synapse - Synaptic transmission
a. Process by which information is transferred from one side of the synapse to the other b. Most adult vertebrate synapses are chemical
c. Electrical impulse that travels down the axon is converted to a chemical message - Neurotransmitter
a. Chemical signal
b. Different neurons use different types of neurotransmitters 5. Receptor
a. Specialized proteins responsible for detecting neurotransmitters b. Involved in transduction of signal
III. Non-Neuronal Cells
A. Glia
1. Support neuronal function
2. Types
a. Astrocytes
b. Oligodendrocytes (Schwann Cells)A. Glia
- Support neuronal function
- Types
a. Astrocytes
i. Regulate extracellular space
ii. Remove neurotransmitters, restrict movement of neurotransmitter from synapse, etc.
b. Oligodendrocytes (Schwann Cells)
i. Myelinating glia
ii. Wrap around the axons
iii. Insulation
iv. Myelin sheath (what holds a sword)
v. Node of Ranvier: where the myelin sheath is interrupted
IV. Functional Activity of Neurons
A. Electrical current created by the movement
B. Properties of action potentials
C. Action potentials occur because of the properties of the neuronal membrane 1. Neuronal membrane is excitable
IV. Functional Activity of Neurons
A. Electrical current created by the movement of ions
- Properties of ions differ from those of electrons
a. Free electrons and more nearly at the speed of light
b. Electrons are good conductors and the air surrounding a wire is not
c. Ions in the cytosol of the nerve cell are less conductive than electrons
d. Fluid around neurons is also a conductor - Membranes are leaky
a. Current moving down an axon leaves passively
i. Like water in a leaky hose - Active process is needed to overcome passive current flow from neuron
a. Action potential
B. Properties of action potentials
- Do not diminish
- Fixed in size and duration (independent of the amount of current that evokes it) 3. All or nothing
C. Action potentials occur because of the properties of the neuronal membrane 1. Neuronal membrane is excitable
IV. Functional Activity of Neurons D. Functional states of a neuron 1. Rest 2. Resting membrane potential 3. Action potential 4. Current plot (look at chart)
- Rest
a. Neurons do not fire continuously
b. When not generating action potentials, neurons are at rest
c. Cytosol along the inside of the membrane has a negative charge relative to the outside - Resting membrane potential
a. Difference in the electrical charge across the membrane
i. Difference is always negative
ii. Can be measured using an intracellular microelectrode - Action potential
a. Brief reversal of the resting membrane potential
b. Electrical signal created during action potential generation is the basic information unit of the nervous system
i. Binary code (actually analogue)
c. Result from the flow of current across the membrane
i. Current is supplied by other neurons - Current plot (look at chart)
a. Potential x time
i. Hyperpolarization
ii. Depolarization
iii. Threshold
V. Properties that Make Action Potentials Possible
A. Three questions B. Resting membrane potential C. Cytosol and extracellular fluid D. Phospholipid membrane E. Proteins associated with the membrane F. Diffusion (One of two primary forces that create resting membrane potentials) G. Electric field (One of two primary forces that create resting membrane potentials) H. Equilibrium state I. Sodium-potassium pump J. Control of ionic movement
V. Properties that Make Action Potentials Possible
A. Three questions
- How does the neuronal membrane at rest separate electrical charge?
- How is this charge rapidly redistributed across the membrane during an action potential?
- How does the impulse (action potential) travel reliably down the axon?
V. Properties that Make Action Potentials Possible
B. Resting membrane potential
- Important considerations
a. Nature of the fluids on the two sides of the membrane b. Structure of the neuronal membrane
c. Proteins that span the membrane
V. Properties that Make Action Potentials Possible
C. Cytosol and extracellular fluid
Fluids are aqueous
Ions
Ionic bond
Charge
- Fluids are aqueous
a. Water distribute charges unevenly
i. Oxygen attracts more negative charge than hydrogen
b. Water is held together by polar covalent bonds
i. An effective solvent for charged molecules - Ions
a. An atom or molecule with a net electrical charge b. Types
i. Cation (+)
ii. Anion (-) - Ionic bond
a. Molecule held together by the electrical attraction of oppositely charged atoms - Charged portion of water has a greater attraction for the ions than they have for each other
a. Ionic bond is broken
V. Properties that Make Action Potentials Possible
D. Phospholipid membrane
Hydrophilic Hydrophobic Lipids Phospholipid bilayer Functional consequence
- Terms
a. Hydrophilic: water loving
i. Polar compounds and ions - Hydrophobic: water fearing
a. Nonpolar covalent bonds
i. Do not interact with water - Lipids
a. Water insoluble biological molecule - Phospholipid bilayer
a. Tail
i. Long chain of carbons
ii. Nonpolar b. Head
i. Polar end
ii. Comprised of P plus 3 O’s - Functional consequence
a. Tails arrange themselves in a bilayer
i. Tails do not like water
ii. Tails are inside
iii. Heads are outside
V. Properties that Make Action Potentials Possible
E. Proteins associated with the membrane
- Background
Protein.type
Primary, Secondary, Tertiary, Quaternary structure - Ion channels (see pic)
a. Number of individual protein molecules organized to create a pore in the membrane
b. Diameter
c. Selectivity
d. Gating
e. Function
- Background
a. Proteins are the product of gene expression
b. Type and distribution of protein molecule distinguish neurons from other cells
c. Resting and action potentials depend on the special proteins that span the lipid bilayer d. Protein chemistry
i. Primary structure: aa chain
ii. Secondary structure: certain types of organizations such as helices and sheets result when certain aa’s are combined in the primary structure
iii. Tertiary structure: individual protein molecules can fold and form a more highly organized structure (e.g. globule)
iv. Quaternary structure: when different polypeptides combine to for a larger molecule - Ion channels
a. Number of individual protein molecules organized to create a pore in the membrane i. Membrane spanning protein
b. Diameter of the pore limits what can pass through the channel
c. Selectivity is also conferred by the nature of the amino acids that line the inside of the pore
i. Positively charged amino acids will attract negatively charged ions
ii. Negatively charged amino acids will attract positively charged ions
d. Gating
i. Unique micro-environmental conditions that alter the selectivity of an ion channel changes (e.g., when voltage changes)
ii. Only when the membrane is within a particular voltage range does the channel open
e. Function
i. Permit and control movement of charged molecules across the neural membrane ii. Movement is selective: size, charge and environmental condition
V. Properties that Make Action Potentials Possible
F. Diffusion (One of two primary forces that create resting membrane potentials)
- Net movement of ions from a higher concentration to a lower concentration
- Ions will not pass through the membrane
a. Can diffuse through ion channels selective for that particular ion - Concentration gradient
a. Difference in concentration between one side and the other
b. Solute will move down its concentration gradient - Factors necessary for diffusion of ions across the neuronal membrane
a. Ion channel for that ion
b. Concentration gradient - Ions will flow down a concentration gradient
V. Properties that Make Action Potentials Possible
G. Electric field (One of two primary forces that create resting membrane potentials)
- Ions can also move as a result of an electric field
- Background
a. Opposite charges attract and like charges repel. (Na+ moves towards negative field and Cl- moves towards positive field)
b. Anode
i. Positive pole of a battery
ii. Negative flow to here c. Cathode
i. Negative pole of a battery
ii. Negative flow away d. Electric current
i. Movement of charges e. Electrical potential (voltage)
i. Difference in charge between the anode and the cathode
ii. Reflects the force exerted on a charged particle f. Electrical conductance
i. Ease with which a charged particle can move g. Resistance
i. Difficulty with which a charged particle can move - Factors necessary for charged particles to move across the neuronal membrane
a. Ion channel for that ion
b. A potential difference across the membrane
Example: K+ of differing concentration separated by a semi-permeable membrane. This difference generates an electrical potential. The side with the higher concentration is negative. If the ions were allowed to freely move, the movement will stop at some point, but not when the concentrations are equal. As positive charges accumulate on one side, the positivity makes it less attractive to positive ions-the potential charge across the membrane offsets the concentration gradient. The point at which this occurs is known as electrochemical equilibrium. This relationship is described by the Nernst equation.
In biological systems, there multiple ions involved, each governed by a separate permeability factor. This relationship is described by the Goldman equation.
two primary forces that create resting membrane potentials
1) Electric field
2) Diffusion
V. Properties that Make Action Potentials Possible
H. Equilibrium state
H. Equilibrium state
- Diffusional and electrical forces are equal and opposite
- For neurons, when these forces are balanced, the resting membrane potential is negative (see below)
V. Properties that Make Action Potentials Possible
Overview
- Neuronal membrane acts as a barrier to charges
a. Permits generation of concentration gradients
b. Permits generation of electric fields - Membrane has ion channels that are selective for ions of different ions
a. Specific ions can move under particular condition
V. Properties that Make Action Potentials Possible
I. Sodium-potassium pump
- Necessary for the inside of the neuron to become negative relative to the outside of the neuron 2. Membrane associated protein
a. Transfers ions across the membrane at the expense of metabolic energy i. 70% of all brain energy is consumed by this pump - Net movement of ions
a. 3 Na+’s from the inside to the outside
b. K+’s are moved into the neuron - Result
a. Both electrical and a concentration gradients are created
b. Na+ is greater outside
c. K+ is greater inside
d. More positive ions outside than inside
i. Inside of the neuron is negative relative to the outside
V. Properties that Make Action Potentials Possible
J. Control of ionic movement
- K+
- Na+
- K+
a. K+ wants to move out based on the difference in concentration b. K+ is attracted to the relative negative charge inside the neuron c. Balance of these forces creates the resting potential - Na+
a. Na+ wants to move in based on the difference in concentration b. Na+ is attracted to the relative negative charge inside the neuron c. Tightly gated Na+ channels prevent the movement of Na+
d. Channels will not open unless a certain voltage range exists
i. Threshold (see below)
VI. Action Potentials
A. Definition B. Voltage versus time plot C. Permeability changes underlie the action potential D. Refractory periods E. Initiation of an action potential F. Falling phase of the action potential G. Voltage gated Na+ channels H. Voltage gated K+ channels
VI. Action Potentials
A. Definition
A. Definition
- Rapid reversal of the resting potential
a. For an instant the inside of the neuron becomes positive relative to the outside
VI. Action Potentials
B. Voltage versus time plot
B. Voltage versus time plot
- Terms
a. Rising Phase
b. Overshoot
c. Falling Phase d. Undershoot
e. Depolarization
i. Less negative
f. Threshold
i. Critical level of depolarization needed for an AP
g. Hyperpolarization
i. More negative
VI. Action Potentials
C. Permeability changes underlie the action potential
See picture
- Selective increase in Na+ conductance coincident to the rising phase a. Na+ is responsible to AP initiation
b. Positive feedback loop causes increased Na+ conductance
c. Na+ conductance slowly activates K+ conductance
d. Na+ conductance inactivates (see below) - Selective increase in K+ conductance coincident to the falling phase
VI. Action Potentials
D. Refractory periods
D. Refractory periods
- Absolute refractory period
a. Time period during which it is not possible to generate an AP - Relative refractory period
a. Time period during which additional depolarizing current is necessary to generate an AP - Absolute and relative refractory periods are dependant on the properties of the ion channels that are involved in the AP (see below)
VI. Action Potentials
E. Initiation of an action potential
1. At rest:
2. Effect of opening Na+ channels
E. Initiation of an action potential
- At rest:
a. Na+ channels are closed
b. A concentration gradient and an electrical potential exist because of the Na+/K+ pump c. K+ channels are closed but leaky
i. Diffusional and electrical forces in balance (K+ wants to stay and leave at the same time) - Effect of opening Na+ channels
a. Na+ would move down its concentration gradient and towards the negative potential b. Inside of the neuron becomes positive relative to the outside
c. Na+ influx accounts for the rising phase of the action potential
VI. Action Potentials
F. Falling phase of the action potential
F. Falling phase of the action potential
- Leaky K+ channels open
a. K+ leaves by flowing down its concentration gradient, away from the now positive (inside) side of the membrane towards the more negative side of the membrane
VI. Action Potentials
G. Voltage gated Na+ channels
- Highly selective for Na+
- Opened and closed by changes in the electrical potential of the membrane
a. When the resting potential is changes from -65mV to -45mV i. Channels opens
b. Channels inactivate (close) spontaneously after approximately 1msec (inactivate) c. Cannot “de-inactivate” until the neuron returns to its resting membrane potential
i. Responsible for the absolute refractory period
VI. Action Potentials
H. Voltage gated K+ channels
- Opening is delayed
a. Coincides with the closing of the Na+ channels - K+ channels do not inactive
- K+ continues to flow out of the neuron until it reaches its ionic equilibrium 4. Voltage inside the neuron will briefly be hyperpolarized
a. Less negative than the resting potential b. Relative resting membrane potential
i. Additional current (more depolarizing current) would be required to reach threshold
Neurotransmission and Neurochemistry
I. Background
A. Sequence of events
1. Action potential generation
2. Propagation of action potential along axon 3. Intra-neuron communication
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
see pic
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
A. Active process is required
A. Active process is required
1. Current not sufficient to generate an action potential is passively conducted
- Current leaks across the axonal membrane
a. Magnitude of the voltage change decays i. Exponential decay
ii. Decay increasing distance from the site that the current was introduced - Leakiness of the axonal membrane prevents effective passive transmission (see pic)
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
B. Action potential occurs without decrement along the entire length of the axon
- Action potential propagation is not passive
- Action potentials have conduction velocity
a. Occurrence time differs as a function of distance from stimulation site
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
C. Mechanism involves the passive spread of current
- Current created by inward movement of Na+ associated with action potential
- Depolarizing stimuli (see below) locally depolarize the axon
a. Open voltage-gated Na+ channels
b. Cause the influx of Na+ - Current flows passively down the axon
a. Depolarizes adjacent areas of the axon
i. Opens Na+ channels in those areas
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
D. Action potential can only propagate away from the source of the depolarizing current
- Na+ channels inactivate
2. Do not “deinactivate” until the membrane returns to resting membrane potentials
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
E. Process
E. Process
- Na+ channels open in response to stimulus
a. Action potential at that site - Depolarizing current passively flows down the axon
- Local depolarization causes adjacent Na+ channels to open and generate an action potential
a. Upstream Na+ channels inactivate b. K+ channels open
i. Membrane repolarizes
ii. Membrane is refractory - Process is repeated in neighboring segment
a. Impulse is propagated
Neurotransmission and Neurochemistry
II. Propagation of Action Potential
F. Site of action potential in vivo
F. Site of action potential in vivo
- Axon
- Axon hillock
a. Small part of the soma where the axon originates - Function of the density of Na+ and K+ channels
Fuse Example:
- Strike a match and light the fuse, like reaching threshold
- As a fuse burns, it ignites the combustible material just ahead 3. It burns only in one direction
Neurotransmission and Neurochemistry
III. Conductance Velocity
A. Factors affecting velocity
B. Saltatory conduction
Neurotransmission and Neurochemistry
III. Conductance Velocity
A. Factors affecting velocity
- Axon diameter
a. Direct relationship
i. Increase diameter, increase velocity
b. Physiologically limiting - Saltatory conduction
Neurotransmission and Neurochemistry
III. Conductance Velocity
B. Saltatory conduction(see figure)
- Myelin
a. Function as insulation
i. Promotes movement of current down the axon
ii. Equivalent to increasing the thickness of the axonal membrane 100 fold
iii. Reduces membrane capacitance
iv. Rate of passive spread is inversely proportionate to membrane capacitance
v. Distance that the current spreads down the inside of the axon and causes an AP is enhanced by myelin
b. Produced by glia
i. Schwann cells in the periphery ii. Oligodendrocytes in the CNS
c. Nodes of Ranvier
i. Intermittent breaks in the myelin
ii. Site of action potential regeneration - Time for an action potential to occur is rate limiting a. Eliminate action potentials
b. Impulse travels faster
IV. Events at Synapse
A. Background (see image)
Types of synapses Neurotransmitter Active zone Postsynaptic density Neurotransmitter receptor Synaptic vesicle
- Types of synapses a. Electrical
i. Rare in adult mammalian NS
ii. Gap junction
iii. Current flows directly through a specialized protein molecule—connexon iv. Distance between the two sides of the membrane is very small (5nM)
b. Chemical
i. Predominant type - Terminology
a. Neurotransmitter
i. Chemical used to communicate with the postsynaptic membrane b. Active zone
i. Site of neurotransmitter release c. Postsynaptic density
i. Contain neurotransmitter receptors
ii. Intercellular chemical messages converted into intracellular signal iii. Occurs in the postsynaptic cell
d. Neurotransmitter receptor
i. Specialized protein molecules that bind the chemical signal ii. Transduces chemical signal into an intracellular message iii. Nature of response depends on receptor type
e. Synaptic vesicle
i. Membrane spheres containing neurotransmitter
IV. Events at Synapse
B. Events at chemical synapse (see image)
Neurotransmitters
Action Potential
Intracellular Ca2+
Neurotransmitter diffuses across the synaptic cleft
- Neurotransmitters are synthesized and stored in synaptic vesicles a. Takes place in the golgi apparatus
b. Transported via secretory granules - Action Potential arrives at the axon terminal a. Opens a voltage gated Ca2+ channel
- Intracellular Ca2+ concentrations signals the neurotransmitter to be released a. Exocytosis
i. Process by which vesicles release their contents b. Vesicles fuse with the active zone
c. Not known how Ca2+ acts as the signal - Neurotransmitter diffuses across the synaptic cleft
a. Binds to its receptor on the postsynaptic membrane
b. Postsynaptic action depends on the nature of the receptor
i. Events are summed over time and space (see below) 5. Neurotransmitter inactivation
a. Information in the brain is based primarily on the frequency of the signal (#/sec)
b. The magnitude of the postsynaptic response needs to be in proportion to the presynaptic signal
i. Preserves the integrity of the message
ii. Chemical message must be controlled
c. NT must be inactivated
i. Degradation
ii. Reuptake
iii. Diffusion
iv. Bioconversion
V. Neurochemistry
A. Background B. Information transfer occurs at synapses C. Chemical communication in the human brain depends on: D. Nature of chemical messages E. Classification F. Cholinergic neurons G. Catecholaminergic neurons H. Serotonergic (serotonin) neurons J. Amino acidergic neurons
V. Neurochemistry
A. Background
- Neurons in the human brain communicate primarily by the release of small quantities of chemical messenger
a. Neurotransmitters
i. Interact with receptors on neuronal surfaces
ii. Alter the electrical properties of neurons
V. Neurochemistry
B. Information transfer occurs at synapses
- Most synapses use chemical messages released from presynaptic axonic terminals
a. Released in response to depolarization of the terminal
b. Messages diffuse across the synaptic cleft
c. Bind with specialized receptors that span the postsynaptic membrane d. Receptor binding of the chemical messages alters neuronal function
i. Electrical
ii. Biochemical iii. Genetic
V. Neurochemistry
C. Chemical communication in the human brain depends on (see pic)
- Nature of the presynaptically released chemical message
- Type of postsynaptic receptor to which it binds
- Mechanism that couples receptors to effector systems in the target cell
V. Neurochemistry
D. Nature of chemical messages
Criteria for classification
- Criteria for classification as a neurotransmitter
a. Molecule must be synthesized and stored in the presynaptic neuron
b. Molecule must be released by the presynaptic neuron upon stimulation
c. Application of the neurotransmitter directly to the target cell must be shown to produce the same effects as the response produced by the release of the neurotransmitter from the presynaptic neuron - Few chemical substances meet these criteria
V. Neurochemistry
E. Classification - SEE PICTURES _ a few…
- Size
a. Neuropeptides: 3-30 aa’s (e.g., met-enkephalin; endorphin)
b. Small molecule neurotransmitters
i. Individual amino acids (glutamate, aspartate, GABA, glycine, acetycholine)
ii. Biogenic amines (dopamine, norepinephrine, epinephrine, serotonin, histamine) - Neurons that use particular neurotransmitters
a. Cholinergic
b. Catecholinergic
c. Serotonergic
d. Amino acidergic
e. Other (neuropeptides, NO, etc.) - Many neurons release more than a single neurotransmitter
a. Dufferential release is base on the conditions that exist
V. Neurochemistry
F. Cholinergic neurons
- Utilize acetylcholine (Ach-“vagus substance”) as their neurotransmitter.
a. ACh is the neurotransmitter for: i. Neuromuscular junction
ii. Preganglionic neurons of the sympathetic and parasympathetic PNS iii. Postganglionic neuron of the parasympathetic PNS
iv. Basal forebrain and brain stem complexes
b. ACh is synthesized from acetyl coenzyme A and choline
i. Reaction is catalyzed by CAT-choline acetyl transferase
c. ACh is degraded in the synaptic cleft by acetylcholinesterase
V. Neurochemistry
G. Catecholaminergic neurons
- Types
a. Dopamine
b. Norepinephrine c. Epinephrine - Synthesized from the amino acid tyrosine a. Each has a catechol group
- Inactivated by reuptake
a. Substances that block their reuptake, prolong their activity
i. Cocaine
ii. Amphetamine
V. Neurochemistry
H. Serotonergic (serotonin) neurons
H. Serotonergic (serotonin) neurons
- 5-hydroxytryptamine, commonly referred to as 5-HT
- Inactivated by reuptake
- 5-HTergic neurons appear to play a role in the brain systems that regulate mood, emotional behavior, and sleep
a. Compounds like Prozac (SSRI) i. Block reuptake
ii. Prolong activity in the synapse
V. Neurochemistry
I. Diffuse neuromodulatory system
- Catecholaminergic and serotonergic neurons
- Modulate large numbers of neurons
a. Spread diffusely throughout the nervous system - Use similar effector systems (see below)
- Commonalities
a. Cell bodies for these neurons are localized to small populations of cell in the brain stem
b. Each neuron can influence many others
i. Each axon makes a 100,000 or more synapses widely spread across the brain
c. Synapses are designed to release the neurotransmitter into the extracellular fluid
i. Allows the NT to spread and affect many neurons - Sites of dopamine action
a. System I
i. Cells bodies in the substantia nigra ii. Regulates movement
b. System II
i. Cell bodies in the ventral tegmental area (VTA) ii. Involved in reinforcement - Sites of serotonin action
a. Cell bodies are in the raphe nuclei
b. Involved in sleep, mood and emotional behavior 7. Sites of norepinephrine action
a. Cell bodies are in the locus coeruleus
b. Makes the most diffuse contacts of any neurons in the CNS
i. A single neuron can make 250,000 synaptic contacts in the cerebrum
ii. Have a second axon making another 250,000 contacts in the cerebellum c. Contacts are non-specific
i. General regulation of brain activity
ii. Activity is coincident to state of CNS 8. Site of acetylcholine action
a. Basal forebrain
b. Neuromuscular junction (PNS)
V. Neurochemistry
J. Amino acidergic neurons
- Types
a. Glutamate (Glu)
i. Bioconversion to glutamine in neighboring glia
b. Glycine (Gly)
c. Gamma-aminobutyric acid (GABA) - Serve as the neurotransmitters at most CNS synapses
a. Glutamate is the primary excitatory neurotransmitter b. GABA is the principle inhibitory neurotransmitter
VI. Transduction of Chemical Signals
A. Background B. Two major classes of receptors C. Classification based on speed of chemical synaptic transmission D. Ligand-gated ion channels E. G-Protein-coupled receptors
VI. Transduction of Chemical Signals
A. Background
See image 5.23
A. Background
1. Chemical messengers are released from the presynaptic terminal in response to an impulse traveling down the axon
a. Impulse is a unit of information
2. Information needs to be transferred to the postsynaptic neuron
3. Process of transferring information to the postsynaptic neuron is transduction
a. Neurotransmitter binds with a specific receptor protein in the postsynaptic membrane that uniquely
identifies the NT
4. A limited number of chemicals that serve as NT’s
a. NT’s have multiple receptors (sub-types) that bind them
VI. Transduction of Chemical Signals
B. Two major classes of receptors
- Ligand-Gated Ion Channels (Ionotropic)
2. G-Protein-Coupled Receptors (Metabotropic)
VI. Transduction of Chemical Signals
C. Classification based on speed of chemical synaptic transmission
- Types
a. Fast signal transduction
b. Slow signal transduction 2. Factors affecting speed
a. Diffusion of the chemical message across the synaptic cleft and bind with the receptor
b. The time it takes for the receptor to transduce the chemical signal into a functional change in the postsynaptic neuron - Fast neurotransmission
a. Postsynaptic receptor is a transmitter-gated ion channel
i. Ion channels function much more rapidly than G-proteins b. Rate limiting step is time of diffusion
i. Therefore rapid (2-5 msec) 4. Slow neurotransmission
b. Postsynaptic receptor is a G-protein-coupled receptor
i. Rate limiting step is time for G-proteins to elicit their effect ii. 100’s of msec to days
VI. Transduction of Chemical Signals
D. Ligand-gated ion channels
(See picture 5.21)
- Membrane spanning proteins that form a pore
a. Pore is closed
b. NT binds to the receptor
i. Receptor undergoes a conformational change
ii. Pores open
iii. Ions can now pass through (i.e., generate current) - Postsynaptic potentials
a. Excitatory postsynaptic potentials (EPSPs)
i. Bring the membrane potential toward threshold (depolarize)
ii. Cations in or anions out
b. Inhibitory postsynaptic potentials (IPSPs)
i. Move membrane potential away from threshold (hyperpolarize) ii. Anions in or cations out - Effects are transient
a. EPSP’s and IPSP’s can be summed temporally and/or spatially
i. Effects be additive or subtractive b. When enough EPSP’s are summed:
i. Threshold is reached
ii. Action potential results 4. NT has a direct effect on receptor
a. Binding of the NT opens an ion channel
b. Causes a direct change in the membrane potential
VI. Transduction of Chemical Signals
E. G-Protein-coupled receptors
- Process
a. NT is bound to a postsynaptic receptor
b. Receptor proteins activate small protein molecules, called G-Proteins
i. Found inside the postsynaptic neuron c. G-Protein activates an “effector” molecule - Types of effector proteins
a. Ion channels in the membrane
b. Enzymes that synthesize second messengers
i. 2nd messengers can activate other enzymes in the cytosol
ii. Enzymatic action regulates ion channel function and alter cellular metabolism 3. Receptors linked to G-Proteins are referred to as Metabotropic Receptors
a. Can have widespread metabolic effects
VII. Neurotransmitter Receptor Sub-Types
A. Ligand-gated ion channels
(see Image)
- Cholinergic receptors (ACh receptors)
- Glutamate receptors
- GABA receptors
- Cholinergic receptors (ACh receptors)
a. Nicotinic ACh receptor (nAChR)
i. Protein complex comprised of 5 subunits
ii. Subunits are either alpha or beta
iii. Receptors can be sub-typed based subunit type - Glutamate receptors
a. Types (3; 2 are ligand-gated)
i. NMDA-N-methyl-D-aspartate; Na+, K+ and Ca++ (v. Imp. 2nd messenger) ii. AMPA-alpha amino-3-hydroxyl-5-methyl-4-isoxazole-proprionate
iii. MgluR-metabotropic (see below) - GABA receptors
a. GABAA
i. Permeable to Cl-
b. GABAB
i. Metabotropic (see below)
VII. Neurotransmitter Receptor Sub-Types
B. Metabotropic receptors
a. Glutamate
i. mGluR Class 1 - 3 b. Epinephrine (EPI)
c. Norepinephrine (NE) i. NE1
ii. NE2
iii. NE1 iv. NE2 v. NE3
d. Acetylcholine
i. ACh: m1-m5
e. Dopamine
i. D1 – D4
ii. D1A and D1B
iii. D2 – D4 f. GABAB
i. R1 and R2 g. All neuropeptides
h. Serotonin
i. 5-HT1 - 5-HT7
i. Acetylcholine
VIII. Intracellular Effects of G-Proteins
A. Direct modulation of ion channels by G-Proteins
- ACh muscarinic receptors
a. Inhibitory
b. G-protein activates a K+ channel
i. Efflux of K+ ii. Depolarization
VIII. Intracellular Effects of G-Proteins
B. G-Protein induced production of intracellular effectors
a. Adenylate cyclases
b. Phosphatases
VIII. Intracellular Effects of G-Proteins
C. Adenylate cyclase sequence of events (see picture)
- NT bound by receptor
- G-protein activated
- G-protein is generally coupled to effector protein (Adenylate cyclase)
a. Generates a 2nd messenger (cAMP) 4. cAMP–2nd messenger:
a. Directly bind ion channels and open or close them
b. Activate a protein kinase (e.g., protein kinase A-PKA)
i. Phosphorylates target proteins such as ion channels c. Phosphorylation of ion channel:
i. Regulates opening or closing ii. Alters PSP’s
VIII. Intracellular Effects of G-Proteins
D. Phospholipase C sequence of events:
- NT bound by receptor
- G-protein activated
- G-protein is generally coupled to effector protein (Phospholipase C)
a. Generates two 2nd messengers i. Inositol triphosphate-IP3
ii. Diacylglygerol - IP3-can release Ca2+ from intracellular stores
a. Increases calcium alters particular ion channels 5. Diacylglygerol
a. Activates protein kinase C
i. Regulates gating of many different types of ion channels
VIII. Intracellular Effects of G-Proteins
A. Direct modulation of ion channels by G-Proteins
B. G-Protein induced production of intracellular effectors
C. Adenylate cyclase sequence of events (see picture)
D. Phospholipase C sequence of events:
IX. Neurotransmitters Can Alter Gene Expression (CREB)
See picture
Figure 7.11
