Chapter 5 Flashcards
Otto Loewi
Frog heart experiment: role of vagus nerve and neurotransmitter acetylcholine in slowing heart rate
↳ changed heartbeat = message passed through fluid
Acetylcholine
Activates skeletal muscles in the somatic nervous system
May excite or inhibit internal organs in the autonomic nervous system
↳ excitatory/innibitory action dependent upon the ion channel (not the molecule itself)
Acetylcholine in vagus nerve → inhibits heartbeat
Hormone vs. Neurotransmitter
Neurotransmitter: Chemical released by a Neuron onto a target → binds to postsynaptic cell and has an excitatory or inhibitory effect
Hormone: outside of central nervous system, same chemicals circulate in bloodstream → distant targets, action slower than NT
Otto loewi’s subsequent research
Epinephrine (EP, or adrenaline) → chemical messenger that acts as a hormone and mobilizes body for fight or flight funny stress: works as NT in the CNS
Norepinephrine (NE, or noradrenaline)→ NT found in brain and in sympathetic division of ANS: accelerates heart rate in mammals
Neurotransmitters→ today’s understanding
100 is maximum number of neurotransmitters
Confirmed is 60
Most work being done by 10 → largest influence on human behavior
Electron microscope
Projects beam of electrons through thin slice of tissue
Identify vesicles using these images *
Chemical Synapse
Junction where messenger molecules (NT) are released from one Neuron to excite or inhibit the next
Most synapses in NS are chemical
Pre-synaptic membrane → axon terminal
Where action potential terminates to release the chemical message
Postsynaptic membrane → dendritic spine
The receiving side of the chemical message, where EPSP’s or IPSP’s are generated
Gates and channels NT bind to
Tripartite Synapse
Functional integration and physical proximity of the presynaptic membrane and postsynaptic membrane and their association with surrounding astrocytes
Not a structure within a cell
Microtubule
Transport structure that brings substances to the axon terminal
Synaptic vesicle
Presynaptic
Small membrane-bound spheres that contain one or more neurotransmitters
Storage granule
Presynaptic
Membranous compartment that holds several vesicles → large storage compartment
Anterograde synaptic transmission: steps 1-5
Transmission between cell A and B → presynaptic to postsynaptic
1.) NT is synthesized inside Neuron
2.) packaged and stored within vesicles at axon terminal
3.) then transported to presynapticmembrane and released into cleft in response to action potential
4.) binds to and activates receptors on postsynaptic membrane
5.) then degraded or removed so it no longer will interact with receptor
Step 1: Neurotransmitter synthesis
Synthesized in axon terminal: small-molecule transmitters →made from food consumed → pumped into cell via transporters → protein molecules in cell membrane pump substances across membrane
Synthesized in cell body: peptide transmitters→ created according to DNA → transported on microtubules to axon terminal
Step 2: Neurotransmitter packaging
Regardless of origin: NT in vesicles can be found in 3 locations at axon terminal:
Some warehoused in granules
Some attached to microfilaments
Some attached to presynaptic membrane
Step 3: Neurotransmitter release
Synaptic vesicles loaded with NT dock near release sites on presynaptic membrane
Vesicles are primed to prepare them to fuse rapidly in response to calcium influx
At terminal, AP opens the voltage-sensitive Ca2+ channels
Ca2+ enters terminal and binds to protein complex
Complex causes some vesicles to empty contents into synapse
Step 4: Receptor-site activation
After release, NT diffuses across synaptic cleft to activate receptors on postsynaptic membrane
Transmitter-activated receptors: protein embedded in membrane of cell that has binding site for a specific NT
Properties of receptor determine effect on postsynaptic cell
Postsynaptic neurotransmitter responses
Depolarize the postsynaptic membrane → causing excitatory action on the postsynaptic Neuron (EPSP)
Hyperpolarize postsynaptic membrane → causing inhibitory action on postsynaptic Neuron (IPSP)
Initiate other chemical reactions that modulate excitatory or inhibitory effect or influence other functions on receiving Neuron
Autoreceptor
Self-receptor on presynaptic membrane that responds to the transmitter that the Neuron releases
Retrograde transmission → NT interact with presynaptic cell: feedback loop to regulate NT release
Step 5: Neurotransmitter inactivation
Diffusion: some NT simply diffuse away from synaptic cleft and are no longer available to bind to receptors
Degradation: enzymes in synaptic def break down NT
Reuptake: transmitter brought back into presynaptic axon terminal for reuse
Astrocyte uptake: nearby astrocytes take up NT
Flexibility in synaptic function
If terminal is very active → amount of NT made and stored increases
If terminal is not often used → enzymes in terminal buttons may breakdown excess transmitter
Axon terminals may even send messages to cell body requesting increased supplies of NT
Synapse types: 7 total
Dendrodendritic→ dendrites send messages to other dendrites
Axodendritic→ axon terminal of one Neuron synapses on dendritic spine of another
Axoextracellular→ terminal with no specific target: secretes transmitter into extracellular fluid
Axosomatic → Axon terminal ends on cell body
Axosynaptic → Axon terminal ends on another terminal
Axoaxonic → axon terminal ends on another axon
Axosecretory → axon terminal ends on tiny blood vessel and secretes transmitter directly into blood
Electrical synapses
Very fast → eliminate delays in info flow
Gap junction: fused pre and postsynaptic membrane that allows an action potential to pass directly from one Neuron to next
Excitatory Synapse characteristics
Located on dendrites
Round vesicles
Dense material on membranes
Wide cleft
Large active zone
Inhibitory Synapse characteristics
Located on cell body
Flat vesicles
Sparse material on membranes
Narrow cleft
Small active zone
Excitatory action within a Neuron
Location of excitatory synapse: dendritic tree closer to cell body
Excitation coming in over dendrites and spreading past axon hillock to trigger action potential at initial segment
Inhibitory action within Neuron
Location of inhibitory synapse: Close to initial segment
Best stopped by inhibiting cell body close to initial segment → inhibition blocks or cuts excitation from passing through postsynaptic cell
4 criteria for identifying neurotransmitters
1.) transmitter must be synthesized or present in the Neuron
2.) when active, chemical must be released and produce a response in some target
3.) same response must be obtained if done experimentally
4.) mechanism must exist for removing transmitter
Neurotransmitter may also
Carry message from one Neuron to another by influencing voltage on postsynaptic membrane
Change structure of a synapse
Communicate by sending messages in the opposite direction
Classes of neurotransmitters → 4
Small-molecule transmitters
Peptide transmitters
Lipid transmitters
Gaseous transmitters
Small-molecule transmitters
Class of quick-acting NT
Synthesized inside of cell from dietary nutrients and packaged in Axon terminals
Can be quickly replaced at presynaptic terminal
Some drugs designed to emulate the route of small molecule transmitters
Examples of small-molecule transmitters
Acetylcholine (ACh)→ present at junction of neurons and muscles and the CNS
Amines (common biochemical pathway/relatedness) → dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT)
Amino acids → glutamate: main excitatory transmitter, and GABA: Mann inhibitory transmitter (2 most abundant NT in brain)
Purines→ synthesized as nucleotides: regulate blood flow, sleep, arousal, etc.
Peptide transmitters
Neuropeptides → short, multifunctional amino acid chain that acts as a NT and can act as a hormone
Synthesized through translation of mRNA from instructions in neurons DNA
Most assembled in ribosomes, packaged in membrane by Golgi bodies, and transported by microtubules to axon terminals
Act slowly and not replaced quickly
Wide range of functions:
↳ act as hormones that respond to stress (cortisol)
↳ enable mother to bond with infant (oxytocin)
↳ regulate eating/drinking and pleasure/pain
Have NO direct effects on postsynaptic membrane voltage → activate receptors that indirectly influence cell
Peptic transmitter examples
Opioids → Met-enkephalin, beta-endorphin, dynorphin
Neurohypohyseals → vasopressin, oxytocin
Secretins → secretin, motility, glucagon, growth hormone-releasing factor
Insulins → insulin, insulin growth factors
Gastrins → Gastrin, cholecystokinin
Lipid transmitters
Can’t be stored in resides → created on demand at level of cell membrane
Affect appetite, pain, sleep, mood, memory, anxiety, stress response
Endocannabinoids → Lipid transmitter
Synthesized at postsynaptic membrane to act on receptors at the presynaptic membrane → postsynaptic Neuron reduces amount of incoming neural signal: Reduces amount of small-molecule transmitter being released
Hypothesized: synthesized on demand after a Neuron has depolarized and calcium has entered
CB1 receptor is target of all cannabinoids
Found at both glutamate and GABA synapses
↳ act as neuromodulators to inhibit release of glutamate and GABA
↳ thus dampen neuronal excitation and inhibition
Gaseous and ion transmitters
Gaseous → synthesized in cell as needed: not stored in synaptic vesicles; easily can cross cell membrane
↳ chemical messengers in body→ modulate NT production
Ion transmitters → zinc as transmitter: actively transported,packaged into vesicles (usually with another transmitter ie. Glutamate) and released into cleft
Ionotropic receptors
Embedded membrane protein with two parts:
- binding site for a NT and a PORE that regulates ion flow to directly and rapidly change membrane voltage
Allows movement of ions such as Na+, K+, and Ca2+ across a membrane
When neurotransmitter attaches to binding site, the pore opens or closes, changing flow of ions
Metabotropic receptor
Embedded membrane protein with a binding site for a NT but NO PORE
Indirectly produces changes in nearby ion channels or in the cells metabolic activity
Linked to a G protein that can affect other receptors or act with second messengers to affect other cellular processes
Amplification Cascade → metabotropic receptor
A single NT binding to a metabotropic receptor can activate an escalating sequence of events
Protiens can be activated or deactivated
Metabotropic receptor coupled to ion channel
Transmitter binds to receptor
Activates gene protein then ion channel is indirectly activated
The cx subunit of the G protein binds to a channel causing a structural change in the channel that allows ions to pass through it
Metabotropic receptor coupled to an enzyme
Transmitter binds to receptor
Binding of transmitter triggers the activation of a G protein in both reactions
The cx subunit binds to an enzyme which activates a second messenger
The second messenger can activate other cell processes
Receptor subtypes
Neurotransmitter → ionotropic → metabotropic
Acetylcholine → nicotinic→ 5 muscarinic
Dopamine → none → 5 dopamine
GABA → GABAa → GABAb
Serotonin → 5-HT3 → 12 5-HT
Neurotransmitter systems and behavior
A single Neuron may use one transmitter at one synapse and a different transmitter at another
Different transmitters may coexist in the some terminal or synapse or even vesicle
Caution against cause-and-effect assumptions regarding relationship between NT and behavior
Neurotransmission in Somatic nervous System
Cholinergic Neuron (motor neurons) → use acetylcholine as its main neurotransmitter: excites skeletal muscles to cause contractions
Nicotinic ACh receptor (nAChr)→ opens exclusively to ACh and depolarizes muscle fiber: when ACh or nicotine binds to this receptor, its pore opens to permit ion flow, depolarizing muscle fiber
The nicotinic receptor pore permits the simultaneous efflux of K+ and influx of Na+
Activating System of ANS → sympathetic
Sympathetic division: arouses body for action, producing fight-or-flight response
Controlled by acetylcholine neurons that emanate from CNS (spinal cord) → CNS neurons synapse with sympathetic neurons that contain norepinephrine
Cholinergic neurons in CNS synapse with NE neurons to produce fight or flight
During sympathetic arousal norepinephrine turns up heart rate and turns down digestive functions
↳NE receptors on heart = excitatory
↳NE on gut = inhibitory
Activating System of ANS → parasympathetic
Controlled by acetylcholine neutrons that emanate from 2 levels of spinal cord
Cholinergic neurons in CNS synapse with autonomic ACh neurons in parasympathetic division to prep body for rest-and-digest
Acetylcholine turns down heart rate and turns up digestive functions because receptors on these organs are reversed:
On heart = inhibitory
On gut = excitatory
Enteric nervous System
Can act without input from CNS
Uses all four classes of NT → more than 30: mainly serotonin and dopamine
Sensory ENS neurons detect mechanical and chemical conditions in the gastrointestinal system
Neurons attached to gut lining
4 activating systems in CNS
Cholinergic, dopaminergic, noradrenergic, and serotonergic→ one system for each small-molecule transmitter
Activating system: neural pathways that coordinate brain activity through a single NT
↳ cell bodies lie in a nucleus in the brainstem, and their axons are distributed throughout brain
Cholinergic System
Normal waking behavior → thought to function in attention and memory
Loss of cholinergic neurons associated with Alzheimer disease
Dopaminergic System
Involved with movement and motor behavior
Nigrostriatal pathways: active in maintaining normal motor behavior (coordination) → loss of DA is related to muscle rigidity and dyskinesia in Parkinson disease
Mesolimbic pathways: dopamine release causes repetition of behaviors → most affected in addiction behaviors: related to impulse control
Increases in DA may be related to schizophrenia
Decreases in DA activity may be related to deficits of attention
Noradrenergic System
Norepinephrine plays a role in learning by stimulating neurons to change structure
Also may facilitate normal development of the brain and organize movements
Imbalances associated with depression and mania
Decreased NE activity related to ADHD and hyperactivity
Serotonergic System
Plays a role in wakefulness and learning → maintaining waking EEG pattern
Imbalances associated with depression, schizophrenia, obsessive-compulsive disorder, sleep apnea, sudden infant death syndrome
Neuroplasticity
The nervous systems potential for change, which enhances its ability to adapt
Required for learning and memory → reconfigure synapses and tissues to maximize learning
Cells that fire together wire together
Hebb Synapse
Axon of cell A near enough to excite cell B and repeatedly takes part in firing it, some metabolic change or growth process takes place in one or both cells → A’s efficiency as one of the cells firing B is increased
2 neurons proximal to each other → I cell fires enough → firing rate influences other cell → strengthen neural connections
Cells that fire together wire together
Eric Kandel and Aplysia → habituation
Awarded 2000 Nobel prize for basis of learning experiment using Aplysia (snails)
Used enduring changes in simple defensive behaviors to study underlying changes in nervous system
Habituation: learning behavior in which a response to a stimulus weakens with repeated presentations of the stimulus → Gill withdrawal response to being sprayed with water: lessened
Neural basis of habituation
Habituation develops → excitatory postsynaptic potentials in motor neuron become smaller: motor neuron is receiving less NT from sensory neuron across synapse (limit action potentials)
Habituation must take place in axon terminal of sensory neuron
Less activity from a habituated Neuron relative to nonhabituated one → Ca2+ influx decreases in response to voltage changes
Less Ca2+ influx results in less NT being released → opposite of sensitization
Reduced sensitivity of Ca2+ channels and decreased release of NT
Sensitization response
Learning behavior where response to stimulus strengthens with repeated presentations BECAUSE stimulus is novel or stronger than normal
Present Stimulus once, wait a while, show more powerful stimulus
Neural basis of sensitization
Response to action potential on axon of sensory Neuron → K+ channels are SLOW to open
K+ ions cannot repolarize membrane quickly → AP last longer than normal: prolongs inflow of Ca2+ and more transmitter is released
More Ca2+ influx results in more transmitter being released → opposite of habituation at molecular and behavioral levels
Learning relative to 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 → can persist for MONTHS
Number and size of sensory synapses CHANGE
↳ habituated: less connections due to overstimulation
↳ sensitized: builds more connections
Transcription and translation of nuclear DNA initiates structural changes → formation of new synapses and spines
Second-messenger cAMP molecule plays important role in carrying instructions regarding structural changes to nuclear DNA
