Chapter 3 - Neurotransmission Flashcards
Neurotransmission
Transmission of info between neurons; involves a release of chemical(s) from pre synaptic neuron into a synapse following an action potential; action of a chemical on adjacent post synaptic neuron
Electric potential
Local difference between the electrical charge inside and outside of a neuron (across cell membrane)
Depolarization
Reduction in the electric potential; brings neuron closer to firing threshold
Hyperpolarization
Increase in the electric potential; moves neuron away from firing threshold
When is a neuron polarized?
At rest (-70mV)
Resting potential
The electrical potential when neuron is not firing (-70mV); remains relatively stable
Action potential
Rapid depolarization of an axon; becomes positive inside
What happens during an action potential?
Begins at axon hillock; happens when another neuron depolarizes cell; firing threshold (-55mV) must be reached; Na+ channels open; Na+ rapidly enters cell; inside of cell reverses polarity locally (+30mV); Na+ channels close and K+ exits
Refractory period
Time during which resting potential is being restored
“All or none” law
Neuron never partially fires; if firing threshold is not reached it will not fire
Firing rate
Depends on the amount of stimulation by other neurons; is limited by the refractory period (cell needs to reset)
Propagation
Conduction of an action potential down an axon; begins at axon hillock; Na+ channels open in succession down axon; speed along axon depends on diameter of neuron
Saltatory conduction
Occurs in axons that are myelinated; results in “skipping” action down neuron (increases speed of propagation)
Neurotransmitters
Signalling molecules for neuronal communication; synthesized by neurons; released from nerve terminals; have effects on other neurons or glands/muscles in periphery; main site of action for most psychoactive drugs
Synthesis (neurotransmitter lifecycle)
Usually made from precursor molecules (ex. Amino acids); either in nerve terminals or in somas
Storage (neurotransmitter lifecycle)
If not used immediately, contained within vesicles that protect from degradation enzymes
Release (neurotransmitter lifecycle)
In response to action potentials; voltage dependent Ca++ channels to open; vesicles bind to presynaptic membrane and released into synapse
Binding to receptors (neurotransmitter lifecycle)
Ligands bind to protein receptors on post-synaptic neurons
Termination of action (neurotransmitter lifecycle)
Several methods to stop action of neurotransmitter (ex. Catabolism by enzymes, re-uptake)
Receptors
Specialized proteins embedded in neuronal membranes to which neurotransmitters bind and activate; binding depends on location and type of receptor; can have immediate (change local potentials) or long term effects (alter gene expression/protein synthesis); a given NT may have several types of receptors (different effects)
Post synaptic receptors
Located on post-synaptic neuron
Pre synaptic neuron
Located on pre synaptic neuron
Auto-receptors
Stimulated by NT released from pre synaptic neuron; inhibit pre synaptic neuron
Heteroreceptors
Stimulated by other NTs (not released from pre synaptic neuron); not same class of NT released by pre synaptic neuron; may increase or decrease pre synaptic neuron
Ionotropic (classes of receptors)
Receptor is coupled to an ion channel embedded in the neuron membrane; when NT binds to the receptor, ion channels open; ions (Na+ Cl-) enter the cell; local membrane potential is either depolarized or hyperpolarized; effect ends when NT is no longer bound to receptor
Metabotropic (types of receptors)
Receptor is coupled to a G protein (not an ion channel) embedded in the neuron membrane; when NT binds to the receptor, G protein is activated in the cell; initiates intracellular signalling
Amino acids (types of NT)
Glutamate, gamma aminobutyric acid (GABA)
Monoamines (type of NT)
Catecholamines (dopamine, norepinephrine, epinephrine); indoleamines (serotonin, melatonin)
Neuropeptides (type of NT)
Endorphines (beta-endorphin, met-enkephalin)
Gases (type of NT)
Nitric oxide
Most NTs are synthesized from ____
amino acids
Glutamate
Synthesized from glutamine (AA in diet) in neurons; converting enzyme (glutaminase); transported into vesicles within producing neuron; released in high quantities in cortex
Glutamate termination
Transported back into releasing cells and restored OR broken down into glutamine (glutamine synthetase)
Glutamate receptors
3 ionotropic (post-synaptic) receptors: NMDA, APMA, kainate receptors
Astrocytes
Play an important role in regulating glutamate neurotransmission; have glutamate receptors and transporters; may break down glutamate into glutamine
GABA (gamma amino butyric acid)
Derived from glutamate by an enzyme (glutamic acid decarboxylase); most abundant inhibitor; receptors: GABAA, GABAB
GABAA Receptor
ionotropic; coupled to Cl- ion channel; hyperpolarizes post synaptic neurons; widespread distribution in brain; site of action of depressants
GABAB Receptor
Matabotropic; coupled to G protein; inhibitory effects
Astrocytes (GABA)
Termination of GABA neurotransmission; GABA taken up by transporters on astrocytes; metabolize GABA into glutamate/glutamine
Monoamines
Single amine group (NH2) in chem structure; target of many psychoactive drugs ex. Dopamine (reward/addiction, movement), norepinephrine (mood, arousal, attention), serotonin (mood)
two classes: catecholamines, indoleamines
Dopamine synthesis
First NT in catecholamine synthesis pathway; tyrosine first converted to L-DOPA via the enzyme tyrosine hydroxylase
Dopamine receptor families
D1 (D1 & D5): excitatory on post synaptic neurons
D2 (D2, D3, D4): inhibitory on post synaptic neurons
All metabotropic
Dopamine termination of action
- Catabolism by enzymes monoamine oxidase (degrade all monoamines) and catecol-O-methyl transferase (only break down catecholamines) 2. Reuptake
Mesolimbic dopamine pathway
From VTA (midbrain) to limbic areas, notably nucleus accumbens, amygdala, hippocampus
Mesocortical dopamine pathway
From VTA to neocortex incl. pre frontal cortex; over-activation associated with schizophrenia; target of anti-psychotic drugs
Nigrostriatal dopamine pathway
From substantia nigra (midbrain) to basal ganglia; degradation = Parkinson’s
Tubero-infundibular dopamine pathway
From PVN of hypothalamus to posterior pituitary; controls release of prolactin
Norepinephrine synthesis
Next NT in catecholamine synthesis in pathway after DA; DA is converted by an enzyme into NE
Norepinephrine receptors
All metabotropic
Two families: alpha and beta
a1 (excitatory), a2 (inhibitory, pre synaptic auto receptors), b1/2/3 (excitatory)
NE termination
Catabolic enzymes or reuptake
Norepinephrine pathway
locus coeruleus (hindbrain) projects to cerebral cortex/amygdala/hippocampus
Serotonin synthesis
In serotonergic neurons; synthesized from essential AA tryptophan; stored in vesicles; also produced in gut cells
Serotonin receptors
Seven major types: 5-HT1 to 7
Subtype 5-HT1A
Most are excitatory
Serotonin termination
- monoamine oxidase
- reuptake: serotonin transporters on pre synaptic neurons (SSRIs block these receptors)
Serotonin pathways
Raphe nuclei in midbrain projects to several regions of brain (forebrain); also to spinal cord to regulate pain; regulates pain and food intake
Acetylcholine (ACH) synthesis
In cholinergic neurons; synthesized from choline (diet) and acetyl coenzyme A
nicotinic (ACH cholinergic receptors)
named for nicotine; ionotropic (excitatory); coupled to pos ion channels Na+ K+ Ca++
muscarinic (ACH cholinergic receptors)
named for muscarine; facilitates ACH neurotransmission; metabotropic (mostly inhibitory)
Acetylcholinesterase (ACH termination)
breaks down ACH into choline and acetic acid
Nucleus basalis of Meynert (ACH pathways
major source of ACH in basal forebrain; supplies ACH to cortex and limbic areas; very important for memory
note: early treatment for Alzheimer’s attempts to boost ACH levels
Neuropeptides
sequence of amino acids; often produced in somas; sometimes co released with other NTs
Neurotrophins
growth factors
Hormones
signaling molecules that communicate over larger distances carried by blood to distant targets (ex. prolactin, oxytocin, melatonin)
