Chapter 5 Flashcards
Neurotransmitter
chemical released by neuron onto target that has excitatory or inhibitory effect (or other more complex effects)
Hormone
chemical circulating in bloodstream (outside CNS)
Structures of Chemical Synapses (4)
1) Presynaptic membrane
2) Postsynaptic membrane
3) Synaptic Vesicle
4) Synaptic Cleft
Structure of Chemical Synapses
1) Presynaptic membrane
membrane on output side of synapse (axon terminal) that sends out NT
Structure of Chemical Synapses
2) Postsynaptic Membrane
membrane on input side of synapse (dendritic spine) that receives NT
Structure of Chemical Synapses
3) Synaptic Vesicle
membrane structure that contains neurotransmitters
- protects NT from breakdown
- provides measurement (NT in proper quantity)
Structure of Chemical Synapses
4) Synaptic Cleft
gap seperating presynaptic membrane from postsynaptic membrane
- where NT are released when stimulated by AP
Storage Granules
large compartments that hold several synaptic vesicles
(4) Steps of Neurotransmission
1) Synthesis & Storage
2) Release of NT
3) Receptor Activation
4) Deactivation of NT
Neurotransmission
1) Synthesis & Storage
NT derived in 2 ways
Vesicles stored in granules, attached to microfilaments or presynaptic membrane
1) Synthesis & Storage
- (2) ways in which neurotransmitters are derived
- which varieties of NT are synthesized via each process?
1) synthesized in axon terminal from chemical precursors in food/diet that are pumped into cell via transporter proteins
- Small-molecule transmitters
- Transmitter Gases
2) synthesized in soma using DNA code, packaged in vesicles on Golgi bodies & transported on microtubules to axon terminal
* neuropeptides
Storage of Neurotransmitters
- which are stored & which arent?
NO
STORED:
- Small-molecule Transmitters
- Neuropeptides
NOT STORED:
- Transmitter Gases
Neurotransmission
2) Release of NT
AP propagated on presynaptic membrane
- opens vs-Ca2+ channels on terminal
- Ca2+ influx → binds to protein calmodulin
- forms complex
-
complex binds to vesicles on …
- presynaptic membrane → empty contents into synaptic cleft via exocytosis
- microfilaments → replace vesicles ^
2) Release of NT
* Amount of NT released depends on?
1) availability (# of vesicles docked @ membrane waiting to be released)
2) amount of Ca2+ entering axon terminal in response to AP
3) Activation of Receptor Sites
NT released from vesicle diffuses across synaptic cleft to bind to transmitter-activated receptors embedded in postsynaptic membrane
- postsynaptic neuron can be affected in 3 ways (depending on type of NT & receptor)
- also can interact with presynaptic receptors (autoreceptors) to influence cell that released it
3) Activation of Receptor Sites
* (3) ways in which postsynaptic neuron is affected by binding of NT to transmitter-activated receptors
a) Depolarization of postsynaptic membrane causing EPSP (open Na+ ion channels)
b) Hyperpolarization of postsynaptic membrane causing IPSP (open K+ or Cl- channels)
c) Initiation of other chemical reactions:
→ that modulate excitatory or inhibitory effect
OR
→ influence functions of postsynaptic neuron
3) Activation of Receptor Site
-
Autoreceptors
- define
- functions (2)
NT may interact with presynaptic receptors (autoreceptors) that influence presynaptic neuron
Self-receptors in neural membrane that respond to NT released by neuron
- indicates that they received message from their own axon terminals
- monitor message & see how much NT is used
4) Deactivation of NT
- Once message has stopped & NT has done its work,* NT are removed from receptor sites & synaptic cleft in (4) ways
1) Diffusion away from synaptic cleft
2) Degradation via enzymes in cleft or terminal (after reuptake)
3) Reuptake into presynaptic neuron for subsequent re-use
4) Glial uptake
Deactivation of Neurotransmitters
1) Diffusion
NT diffuse away from synaptic cleft & are no longer available to bind to receptors
Deactivation of Neurotransmitters
2) Degradation
by enzymes in synaptic cleft OR in terminal (after reuptake)
Deactivation of Neurotransmitters
3) Reuptake
specific membrane transporter proteins bring NT or by-products of enzymatic degradation into axon terminal for reuse
Deactivation of Neurotransmitters
4) Glial Uptake
NT taken up by nearby glial cells
- can store for re-export to axon terminal
- enzymatic degradation
Although there are many different types of synapses, which (2) do we discuss?
Axodendritic: axon terminal ends on dendrite (or dendritic spine) of another
Axomuscular: axon synapses with muscle end plate
(2) Classifications of Chemical Synapses
Type I Synapse
Type II Synapse
Type I Synapse
- location
- characteristics/features (5)
excitatory
typically on dendrites
large active zone
wide cleft
round vesicles
denser material on pre/postsynaptic membrane
Type II Synapse
- location
- characteristics/features (5)
inhibitory
typically on soma
small active zones
narrow cleft
flat vesicles (fewer vesicles & receptors)
sparse material on pre/postsynaptic membranes
Which Type of Synapse (I or II) is more influential?
Type II Synapses are more influential since closer to axon hillock
Types of Neurotransmitters
- (4) points
- ~ 50 different kinds
- can be inhibitory at one location & excitatory at another (depending on receptor type)
- >1 can be active at 1 synapse
- NO 1-to-1 relationship between single NT & single behavior
(4) Criteria for Identifying Neurotransmitters
1) Must be synthesized or present in neuron
2) Must be released by active neuron & produce response in target cell
3) Same response must be obtained when chemical is experimentally placed on target
4) Existing mechanism for removal of chemical from site of action after its work is done
Types of Neurotransmitters (3)
1) Small-molecule NT
2) Neuropeptides
3) Transmitter Gases
1) Small-molecule NT
- fast-acting NT
- synthesized from chemical precursors in diet & packaged in axon terminal
- can produce all 3 types of effects
1) Small Molecule Transmitters
* Examples? (3)
Acetylcholine
Amines
Amino Acids
1) Small Molecule Transmitters
* Examples → a) Acetylcholine
acetate (vinegar)
+
choline (fatty foods → egg yolk)
1) Small Molecule Transmitters
* Examples → Amines (4)
Tyrosine = precursor (in diet) for:
→ dopamine
→ norepinephrine
→ epinephrine (adrenaline)
Tryptophan = precursor for:
→ seratonin >>> melatonin
1) Small Molecule Transmitters
* Examples → Amino Acids
Glutamate → GABA
2) Neuropeptides
chains of AAs synthesized in soma from mRNA based on DNA code
- shipped to axon terminal
- often act as hormones
- slower-acting
- replaced slower
- only work at metabotropic receptors*
- activate synaptic receptors that indirectly influence cell structure/function
2) Neuropeptides
* examples (2)
Oxytocin
Endorphins
3) Transmitter Gases
NOT stored in vesicles
synthesized in cell as needed
easily diffuse across cell membrane
3) Transmitter Gases
* examples (2)
Nitric Oxide (NO)
- control intestinal wall muscles, BV dilation in active brain regions & sexual organs (erectioN)
Carbon Monoxide (CO)
→ activate metabolic (E-expending) processes in cells
(2) Classes of Receptors
1) Ionotropic - direct & fast
2) Metabotropic - indirect & slow
1) Ionotropic Receptors
- define
- function
embedded membrane protein with binding site for neurotransmitter & pore (similar to gated channel)
- regulates ion flow to directly & rapidly change membrane voltage
2) Metabotropic Receptors
- define
- general function
embedded membrane protein with binding site for NT
- linked to G protein
→ indirectly produce changes in nearby ion channels OR in cell’s metabolic activity
Metabotropic Receptors → Indirect Effects (2)
NT binds to receptor → triggers G protein activation
→ α subunit detaches
a) binds to ion channel
b) binds to enzyme
Metabotropic Receptors → Indirect Effects
Detached α subunit…
a) binds to ion channel
b) binds to enzyme
binding of α subunit to nearby ion channel causes structural change in channel
→ modifies flow of ions through it
Metabotropic Receptors → Indirect Effects
When detached α subunit…
a) binds to ion channel
b) binds to enzyme
enzyme activates second messenger that carries instructions to other intracellular structures
Metabotropic Receptors → Indirect Effects
When detached α subunit…
b) binds to enzyme
- (3) possible effects
Enzyme activates second messenger, which can…
a) bind to membrane channel → structural change to alter ion flow
b) initiate reaction → causes proteins in cell to become incorporated into membrane (i.e. form new ion channel)
c) instruct DNA to start/stop production of a protein
Neurotransmitter Systems: ANS → SNS
Axons of motor neurons in CNS project to skeletal muscles
- aka cholinergic → ACh = main NT
ACh binds to ionotropic nicotinic receptors (nAChr) on muscle fibers
- opens channels → K+ outflow & Na+ influx
- depolarizes membrane → AP → muscle contraction
Neurotransmitter Systems: PNS → ANS
Both divisions controlled by ACh neurons emanating from CNS
These CNS neurons synapse with…
- Parasympathetic neurons that contain ACh
- Sympathetic neurons that contain NE
metabotropic receptors
Neurotransmitter Systems: CNS
many neuropeptides have specific & localized functions
many small-molecule transmitters have general functions & larger # of targets
Neurotransmitter Systems: CNS
- many neuropeptides have specific & localized functions
- example?
Oxytocin
- as a hormone → role in labor contractions, breastfeeding (milk-drop)
- as a NT → role in bonding between parent/offspring & mates
Neurotransmitter Systems: CNS
- many small-molecule transmitters have general functions
- examples? (3)
GABA → regulates neural inhibition
Glutamate → regulates neural excitation
Activating Systems
Neurotransmitter Systems: CNS
- Many Small Molecule Transmitters have general functions
→ Activating Systems
- define
neural pathways that coordinate brain activity through a single NT
- cell bodies are in nucleus
- axons distributed through wide region of brain
Activating Systems (4)
1) Noradrenergic
2) Serotenergic
3) Cholinergic
4) Dopaminergic
a. nigrostriatial pathways
b. mesolimbic pathways
1) Noradrenergic System
projections from locus coeruleus
- related to attention & arousal
- decreases related to depression & ADHD
- increases related to mania
2) Serotenergic System
- projections?
- general function
- increases/decreases related to?
projections from raphe nucleus in brainstem
related to arousal (wakefulness)
- increases related to schizophrenia
- decreases related to depression
2) Serotenergic System
* targeted by?
antidepressants
extacy
cocaine
3) Cholinergic System
- projections?
- related to?
- role in?
- decreases…
projects from midbrain & basal forebrain nuclei
- related to arousal
- role in memory & attention
-
decreases in ACh related to Alzheimer’s
- loss of cholinergic neurons
4) Dopaminergic System
* operates in (2) distinct pathways
a) Mesolimbic Dopaminergic System
b) NIgrostriatal Dopaminergic System
4) Dopaminergic System → 2 distinct pathways
a) Mesolimbic Dopaminergic System
- projections
- functions (2)
- increases related to?
projects from ventral tegmental area
- role in pleasure & reward
- stimulating this system enhances responses to stimuli → more attractive & rewarding
- mediates drug addiction
- DA in this system is most affected in addiction
- ↑ increases related to schizophrenia (↑mental/motor agitation)
4) Dopaminergic System → 2 distinct pathways
b) Nigrostriatal Dopaminergic System
- projections
- function
- decreases related to?
projects from substantia nigra to striatum (caudate & putamen)
- role in normal motor behavior
- coordinating movement, force/exertion
-
↓ DA decrease related to Parkinson’s
- muscular rigidity & movement release (dyskinesia)
Dopaminergic System → Drugs
Drugs cannot selectively target one pathway of Dopaminergic system
→ causes side-effects as a result
- ex) Drugs to treat Schizophrenia may cause Parkinson’s-like symptoms & vice versa
