Module 5 Neurons' Electrochemical Signals to Communicate and Adapt Flashcards
A Chemical Message
- Discoveries about how neurons communicate stem from experiments designed to study what controls an animal’s heart rate
- Heartbeat quickens if you are excited or exercising; if you are resting, it slows
- Chemicals relay excitatory messages to say “speed up” and inhibitory messages to say “slow down”
A Chemical Message
-Otto Loewi (1921)
- Frog heart experiment
- Role of the VAGUS NERVE and the neurotransmitter ACETYLCHOLINE (ACh) in slowing heart rate
A Chemical Message
-Acetylcholine
-The first neurotransmitter discovered in the PNS and CNS; activates skeletal muscles in the somatic nervous system and may excite or inhibit internal organs in the autonomic nervous system
A Chemical Message
-Otto Loewi’s Subsequent research
~Epinephrine (EP, or adrenaline)
-Chemical messenger that acts as a hormone to mobilize the body for fight or flight during times of stress and as a neurotransmitter in the central nervous system
A Chemical Message
-Otto Loewi’s Subsequent research
~Norepinephrine (NE or noradrenaline)
-Neurotransmitter found in the brain and in the parasympathetic division of the autonomic nervous system; accelerates heart rate in mamals
A Chemical Message
-Neurotransmitter
-Chemical released by a neuron onto a target with an excitatory or inhibitory effect
-Outside the CNS, many of these chemicals circulate in the blood stream as hormones (have distant targets, action slower than neurotransmitter)
~ Hypothalamus -> Pituitary Gland -> Hormones -> Target Organs and Glands
Structure of Synapses
-Electron Microscope
- Projects a beam of electrons through a very thin slice of tissue
- Varying structure of the tissue scatters the beam onto a reflective surface where it leaves an image, or shadow, of the tissue
- Much better resolution than the light microscope
- 1950s: revealed the structure of a synapse for the first time
Structure of Chemical Synapses
-Chemical Synapse
- The junction where messenger molecules (neurotransmitters) are released from one neuron to excite or inhibit the next neuron
- Majority of synapse in the mammalian nervous system are chemical
Structure of Chemical Synapses
-Presynaptic Membrane (axon terminal)
-Where the action potential terminates to release the chemical message
Structure of Chemical Synapses
-Postsynaptic Membrane (dendritic spine)
-The receiving side of the chemical message; EPSPs or IPSPs are generated
Structure of Chemical Synapses
-Synaptic Cleft (space between)
-Small gap where the chemical travels from presynaptic to postsynaptic membrane
Structure of Chemical Synapses
-Synaptic Vesicle (presynaptic)
-Small membrane-bound spheres that contain the neurotransmitters(s)
Structure of Chemical Synapses
-Storage granule (presynaptic)
-Membrane compartment that holds several vesicles containing the neurotransmitter(s)
Structure of Chemical Synapses
-Postsynaptic Receptor (postsynaptic)
-Site to which a neurotransmitter molecule binds
Electrical Synapses
-Gap Junctions
- Fused presynaptic and postsynaptic membrane that allows an action potential to pass directly from one neuron to the next
- Electrical synapses are fast
- Chemical synapses are more flexible (amplify or diminish signal)
Neurotransmission in Four Steps
-The neurotransmitter must be
- Synthesized and stored in the axon terminal
- Transported to the presynaptic membrane and released in response to an action potential
- Able to activate receptors on the target-cell located on the postsynaptic membrane
- Inactivated, or it will continue to work indefinitely
Step 1: Synthesis and Storage
-Neurotransmitters are derived in two general ways
-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
Step 2: Neurotransmitter Release
- At the terminal, the action potential opens voltage-sensitive CALCIUM (Ca2+) channels
- Ca2+ enters the terminal and binds 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 contents
Step 3: Receptor-Site Activation
-After being released, the neurotransmitter diffuses across the synaptic cleft to activate receptors on the postsynaptic membrane
-Transmitter-Activated Receptors
~Protein embedded in the membrane of a cell that has a binding site for a specific neurotransmitter
Step3: Receptor-Site Activation
-On postsynaptic site, neurotransmitter may:
- Depolarize the postsynaptic membrane causing EXCITATORY action on the postsynaptic neuron (EPSP)
- Hyperpolarize the postsynaptic membrane causing INHIBITORY action on the postsynaptic neuron (IPSP)
- Initiate other chemical reactions that modulate either the excitatory or inhibitory effect, or influence other functions of the receiving neuron
Step 3: Receptor-Site Activation
-Neurotransmitter may interact with receptors on the PRESYNAPTIC membrane
-Autoreceptors
~”Self-receptors” on the presynaptic membrane that responds to the transmitter that the neuron releases
Step 4: Deactivation of the Neurotransmitter
-Accomplished in at Least Four Ways
~DIFFUSION away from synaptic cleft
~DEGRADATION by enzymes in the synaptic cleft
~REUPTAKE into the presynaptic neuron for subsequent reuse
~Taken up by neighboring GLIAL CELLS
Varieties of Synapses
- In the nervous system, synapses vary widely, and each type is specialized in location, structure, function, and target
- Wide variety of connections makes the synapse a versatile chemicals delivery system
- Through connections to the dendrites, cell body, or axon of a neuron in different ways
Excitatory and inhibitory Messages
-Type I Synapse
- Excitatory
- Typically located on dendrites
- Round vesicles
- Dense material on membranes
- Wide cleft
- Large active zone
- Found on the Spine
Excitatory and Inhibitory Messages
-Type II Synapse
- Inhibitory
- Typically located on the cell body
- Flat vesicles
- Sparse material on membranes
- Narrow Cleft
- Small active zone
- Found on the neuron cell body
Evolution of Complex Neurotransmission System
-Chemical transmission may have had its origins in the feeding behavior of single-celled creatures
~Digestive juices are secreted onto prey via EXOCUTOSIS (release of neurotransmitter)
~Prey is captured via ENDOCYTOSIS
-This process parallels the use of neurotransmitters for communication
Varieties of Neurotransmitters
- About 50 different kinds have been identified
- Some are inhibitory at one location and excitatory at another
- More than one neurotransmitter may be active at a single synapse
- No simple one-to-one relationship between a single neurotransmitter and a single behavior
Criteria for Identifying Neurotransmitter
- The chemical must be SYNTHESIZED in the neuron or otherwise be present in it
- When the neuron is active, the chemical must be RELEASED and PRODUCE A RESPONSE in some target
- The same response must be obtained when the chemical is EXPERIMENTALLY PLACES on the target
- A mechanism must exist for REMOVING the chemical from its site of action after its work is done
Acetylcholine and the Renshaw Loop
- Main axon projects to muscle; axon collateral remains in spinal cord and synapses with Renshaw inhibitory interneuron
- Motor axon and collateral contain acetylcholine
- When the motor neuron is highly excited, it can modulate its activity levels through the Renshaw loop (plus and minus signs)
Neurotransmitter May Also
-Carry a message from one neuron to another by influencing the voltage on the postsynaptic membrane
-Have a common message carrying function, such as changing the structure of a synapse
-Communicate by sending messages from postsynaptic to presynaptic membrane
~These reverse-direction messages influence the release or reuptake of transmitters
Three Classes of Neurotransmitters
- Small-molecule transmitters
- Peptide transmitters
- Transmitter gases
Small-Molecule Transmitters
-Class of quick-acting neurotransmitters
-Synthesized from dietary nutrients and packaged ready for use in axon terminals
-Examples
~Acetylcholine (ACh)
~Amines:
*Dopamine (DA)
*Norepinephrine (NE)
*Epinephrine (EP)
*Serotonin (5-HT)
~Amino Acids:
*Glutamate (Glu)
*Gamma aminobutyric acid (GABA)
*Glycine (Gly)
Small-Molecule Transmitters
-Acetylcholine Synthesis
-Choline
-Acetate
~Two important enzymes
*Acetyl coenzyme A
*Choline acetyltransferase (ChAT)
-Breakdown of Acetylcholine
~Enzyme
*Acetylcholinesterase (AChE)
Small-Molecule Transmitters
-Sequential Synthesis of Three Amines
-Tyrosine -> L-Dopa -> Dopamine -> Norepinephrine -> Epinephrine
Small-Molecule Transmitters
-Rate-Limiting Factor
-Any enzyme that is in limited supply, thus restricting the pace at which a chemical can be synthesized
-Example:
~Tyrosine hydroxylase in amine synthesis
Small-Molecule Transmitters
-Amino Acid Transmitters
-Glutamate ~Main excitatory transmitter -GABA ~Main inhibitory transmitter *GABA is formed by a simple modification of the glutamate molecule
Peptide Transmitter
-Neuropeptide
~A multifunctional chain of amino acids that act as a neurotransmitter
~Synthesized from mRNA on instructions from the cell’s DNA
~Do not bind to ion channels; do not have direct effects on the voltage of the postsynaptic membrane
-Indirectly influence cell structure and function
-Act as hormones that respond to stress
-Enable a mother or father to bond with her infant
-Regulate eating and drinking and pleasure and pain
-Contribute to learning
-Opiates such as morphine and heroin mimic the actions of natural brain peptides
Transmitter Gases
-Neither stored in synaptic vesicles nor released from them
-Synthesized in call as needed
-Easily crosses cell membrane
-Example
~Nitric Oxide (NO)
~Carbon Monoxide (CO)
Two Classes of Receptors
-Ionotropic Receptor
-Metabotropic Receptor
~No one neurotransmitter is associated with a single receptor type
~A neurotransmitter may
*Bind to an ionotropic receptor and have an excitatory effect on the target cell or
*Bind to a metabotropic receptor and have an inhibitory effect
*Example
**Acetylcholine activates inotropic receptors on muscles for excitation; activates metabotropic receptors on heart to inhibit
Ionotropic Receptor
-Embedded membrane protein with two parts
~A binding site for a neurotransmitter
~A pore that regulates ion flow to directly and rapidly change membrane voltage
~Allows the movement of ions such as Na+, K+ and Ca2+, across a membrane
~When neurotransmitter attaches to binding site, the pore opens or closes changing the flow of ions
Metabotropic Receptor
- Embedded membrane protein with a binding site for a neurotransmitter but NO PORE
- Indirectly produce changes in nearby ion channels or in the cell’s metabolic activity
- Linked to a G-protein that can affect other receptors or act with second messengers to affect other cellular processes
Metabotropic Receptor
-G Protein
-Consists of three subunits
~Alpha
~Beta
~Gamma
-Alpha subunit detaches when a neurotransmitter binds to the G protein’s associated metabotropic receptor
-Detached alpha subunit binds to other proteins within the cell membrane or within the cytoplasm of the cell
Metabotropic receptors
-Second Messenger
-A chemical that carries a message to initiate a biochemical process
-Activated by a neurotransmitter (the first messenger)
-Example
~Alter ion flow in a membrane channel
-Formation of new ion channels
-Production of new proteins through DNA
Neurotransmitter Systems and Behavior
- A single neuron may use one transmitter at one synapse and a different transmitter at another synapse
- Different transmitters may coexist in the same terminal or synapse
- Caution against the assumption of a simple cause-and-effect relation between a neurotransmitter and a behavior
The Somatic Nervous System
-Cholinergic Neuron
~Neuron that uses acetylcholine (ACh) as its main neurotransmitter
-Nicotinic ACh Receptor
~When ACh (or nicotine) binds to this receptor, its pore opens to permit ion flow, thus depolarizing the muscle fiber
The Autonomic Nervous System
-Cholinergic neurons from the CNS control both divisions
~Sympathetic (fight-or-flight- response)
~Parasympathetic (rest-and-digest response)
-Norepinephrine is also involved in the fight-or-flight response
Systems in the Central Nervous System
-Activating System ~Neural pathways that coordinate brain activity through a single neurotransmitter ~Cell bodies are located in a nucleus in the brainstem and their axons are distributed through a wide region of the brain ~Four Systems *Cholinergic *Dopaminergic *Noradrenergic *Serotonergic
Systems in the Central Nervous System
-Cholinergic System
- Normal waking behavior and is thought to function in attention and memory
- Loss of cholinergic neurons associated with Alzheimer’s disease
Systems in the Central Nervous System
-Dopaminergic System
-Nigrostriatal path
~Involved in coordinating movement; degenerates in Parkinson’s disease
-Mesolimbic Path
~Enhances responses to environmental stimuli; implicated in addiction and schizophrenia
Systems in the Central Nervous System
-Noradrenergic System
- Plays a role in learning by stimulating neurons to change their structure; may also facilitate normal development of the brain and organize movements
- Imbalances associated with depression or mania
Systems in the Central Nervous System
-Serotonergic System
- Plays a role in wakefulness and learning
- Imbalances associated with depression, schizophrenia, obsessive-compulsive disorder, sleep apnea
Role of Synapses in Learning and Memory
-Learning
-Relatively permanent change in behavior that results from experience
Role of Synapses in Learning and Memory
-Neuroplasticity
- The nervous system’s potential for change that enhances its ability to adapt
- Required for learning and memory
Role of Synapses in Learning and Memory
-Hebb Synapse
-“When the axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased”
Role of Synapses in Learning and Memory
- Eric Kandel was awarded a Nobel Prize in 2000 for his descriptions of the synaptic basis of learning using APLYSIA
- Used enduring changes in simple defensive behaviors to study underlying changes in the snail’s nervous system
Habituation Response
-Learning behavior in which a response to stimulus weakens with repeated stimulus presentations
-Example
~Gill withdrawal response in the marine snail APLYSIA CALIFORNICA
Neural Basis of Habituation
- As habituation develops, the excitatory postsynaptic potentials in the motor neuron become smaller
- Motor neuron is receiving less neurotransmitter from the sensory neuron across the synapse
- Habituation must take place in the axon terminal of the sensory neuron
- Less neurotransmitter is released from a habituated neuron than from a nonhabituated one
- As habituation takes place Ca2+ influx decreases in response to voltage changes associated with an action potential
- Reduced sensitivity of Ca2+ channels and decreased release of neurotransmitter
Sensitization Response
-Learning behavior in which the response to a stimulus strengthens with repeated presentations of that stimulus because the stimulus is novel or stronger than normal
Neural Basis of Sensitization
- In response to an action potential on axon of sensory neuron, K+ channels are slow to open
- K+ ions cannot repolarize the membrane quickly, so action potential lasts longer than normal
- Prolongs the inflow of Ca2+ and more transmitter is released
- Sensitization is the opposite of habituation at the molecular and behavioral levels
- In sensitization, more Ca2+ influx results in more transmitter being released
- In habituation, less Ca2+ influx results in less neurotransmitter being released
Learning as a Change in Synapse Number
- Neural changes associated with learning must last long enough to account for a relatively permanent change in an organism’s behavior
- Repeated stimulation produces habituation and sensitization that can persist for months
- The number and size of sensory synapses change in well-trained, habituated, and sensitized APLYSIA
- Transcription and translation of nuclear DNA initiate structural changes (formation of new synapses and spines)
- Second messenger cAMP plays an important role in carrying instructions regarding structural changes to nuclear DNA
Bradycardia (Brady “slow” cardia “heart”)
- Conserves the body’s oxygen when you are not breathing is a useful survival strategy
- This energy -conserving response under water is common to many animals
The heart adjusts it’s rate in response to at least two different messages
- Excitatory message
- Inhibitory message
Excitatory Message
-That says speed up
Inhibitory Message
-Says to slow down
Acetylcholine (ACh)
-The same transmitter that activates skeletal muscles
~Loewi’s experiment ACh acts to inhibit heartbeat, to slow it down
-It turns out that ACh excites skeletal muscles in the somatic nervous system, causing them to contract, and may either excite or inhibit various internal organs in the automatic system
~It turns out that the ion channel and it’s associated receptor, not the molecule itself, determine whether the messenger will be excitatory or inhibitory
-ACh is the chemical messenger associated with the slowed heartbeat in diving bradycardia
-First neurotransmitter discovered in the PNS and CNS; activates skeletal muscles in the SNS; either excites or inhibits internal organs in the ANS
Epinephrine (epi “above” nephron “kidney”)(Greek)
Adrenaline (Latin)
- Stimulated a nerve to the heart, the accelerator nerve, and heart rate increased
- Both are the same substance, produced by the adrenal glands located atop the kidneys
- Adrenaline is the name more people know, in part because a drug company used it as a trade name, but epinephrine is common parlance in the science community
- Chemical messenger that acts as a neurotransmitter in the CNS and as a hormone to mobilize the body for fight or flight during times of stress; also know as adrenaline
Norepinephrine (NE)
- A chemical closely related to epinephrine (EP)
- ACh from the vagus nerve inhibits heartbeat, and EP from the accelerator nerve excited it
- Neurotrantmitter that accelerates heart rate in mammals; found in the brain and in the sympathetic division of the ANS; also known as noradrenaline
Neurotransmitters
-Chemical messengers released by a neuron onto a target to cause an excitatory or inhibitory effect
-Outside the CNS, many of the same chemicals, epinephrine among them, circulate in the bloodstream as hormones
~Under control of the hypothalamus, the pituitary gland releases hormones into the bloodstream to excite or inhibit targets, such as organs and glands in the autonomic and enteric nervous systems
-Travel throughout the body to distant targets, their actions are slower than those of CNS neurotransmitters prodded by the lightning-quick nerve impulse
-Chemical with an excitatory or inhibitory effect when released by a neuron onto a target
-The real difference between neurotransmitters and hormones is the distance they travel, within the same body, before they encounter their receptors
Hormones
- Travel throughout the body to distant targets, their actions are slower than those of CNS neurotransmitters prodded by the lightning-quick nerve impulse
- The real difference between neurotransmitters and hormones is the distance they travel, within the same body, before they encounter their receptors
Parkinson’s Disease
-Three findings have helped researchers understand it’s neural basis
~In 1919 Tréatikoff (1974) studied the brains of nine Parkinson patients on autopsy and found that the substantia nigra, a small midbrain nucleus, had degenerated; in the brain of one patient who had Parkinsonlike symptoms on only one side of the body, the substantia nigra had degenerated on the side opposite that of the symptoms
~Chemical examination of the brains of Parkinson patients showed that disease symptoms appear when the level of dopamine (DA), then a proposed neurotransmitter, was reduced to less than 10 percent of normal in the basal ganglia
~Confirming the role of dopamine in a neural pathway connecting the substantia nigra to the basal ganglia, Urban Ungerstedt found in 1971 that injecting a neurotoxin called 6-hydroxydopamine into rats selectively destroyed these dopamine-containing neurons and produced symptoms of Parkinson disease
-Loss of dopamine-containing substantia nigra neurons has been linked to environmental factors such as insecticide, herbicide, fungicides, flu virus, and toxin drugs; about 10% of people with Parkinson disease have a mutation in one of several specific genes, and it may also be the case that people who are susceptible to environmental influences also have a genetic predisposition
-Treatments for neurological diseases are usually much more effective the earlier they are started, so early detection is important
-Motor system disorder correlated with dopamine loss in the substantia nigra; and reduction in voluntary movement
Dopamine (DA)
- Itself in other brain areas has been linked not only to motor behavior but also to some forms of learning and to neural structures that mediate reward and addiction
- Amine neurotransmitter involved in coordinating movement, attention, learning, and reinforcing behaviors
