CNS Synases And Neurotransmitters Flashcards
NT across a synaptic cleft
Apposition of axon terminal to a postsynaptic structure
Chemical synapses
Gap junctions
Direct passage of current
Electrical synapses
Presynaptic and post synaptic membranes contain theses which are critical to synapse formation and activity-induced structural plasticity
Cell adhesion molecules (transmembrane proteins) that bridge the synapse
Do all dendrites have spines
No
What is critical to synapse formation and plasticity?
Cell adhesion molecules span the synapse
Through these protein-protein interactions, synaptic NT can lead to structural and functional changes to the synapses
Postsynaptic receptors are coupled to scaffolding proteins which then link to cytoskeletal proteins
Overview of the path of NT
-neurotransmitter synthesis (precursor entering the cell)
-vesicular transport (NT packed into synaptic vesicles and made outside and brough into vesicle)
-postsynaptic receptor
-NT binds to specific receptor and has excitatory or inhibitory response
-release-modulating autoreceptor (regulate terminal that have inhibitory effect on release of NT)
-NT can leak out of cleft
-clearance by astrocytes transporter
(Cleans up left over NT)
Enzymatic synthesis of NT
Enzymes (and empty synaptic vesicles) must be axonally transported from soma to terminal
Local synthesis of NT in axon terminals by enzyme located either…..
In cytoplasm or inside synaptic vesicles
If NT synthesized in cytoplasm, needs tranlocated unto synaptic vesicle by what
Selective transporter protein in vesicular membrane
Where are neuropeptides transcribes and translated?
In soma and modified in the Golgi
Axonal transport of neuropeptides
Transport of neuropeptide-containing vesicle to terminals
NT synthesis Is followed by sequestration into vesicles how?
Protein pump: ATP-dependent
Flow down EC gradient
The H+ going down the gradient supplies the energy
Exceptions to NT sequestration into vesicles
- some NT synthesized by enzymes located inside synaptic vesicles from precursor molecules that must be sequestered by the vesicular membrane transporter
- neuropeptides transmitters are synthesized and sequestered in the soma, then vesicles undergo anterograde axonal transport to terminal
Vesicles at rest
Few are already docked at active zone, most vesicles are tethered by actin and not yet docked
Vesicles after AP and Ca++ influx
- Ca influx allows NT release by pre-docked vesicles
- Ca influx causes actin filament to de-polymerize, dis-associate from vesicles dock, fuse, and release, vesicles are recycled
Ionotropic post synaptic receptor
Ion channel
Metabotropic post synaptic receptor
Coupled to 2nd messengers, usually G protein
Classical small molecule NT
- Ach
- amino acid NT
- biogenic amines
- indolamines
Examples of amino acid NTs
- glutamate
- GABA
- histamine
Major excitatory NT in CNS
Glutamate
Y-aminobutryic acid, major inhibitory NT in CNS
GABA
Some neurons in hypothalamus, involved in wakefulness
Histamine
What are some biogenic amines
Cathecholamines
- dopamine
- norepi
- epi
Example of indolamine
Serotonin
What are monoamines?
All biogenic amines and indolamines
- dopamine
- norepi
- epi
- serotonin
Neuropeptidess in CNS
-substance P (peripheral nerves, spinal cord, pain related)
-endogenous opiates (enkephalins, dynorphins, B-endorphin)
-orexin aka hypocretin (hypothalamus, regulates hunger and sleep)
Hypothalamic peptide hormones (function elsewhere in CNS as NT
Neuropeptides of the CNS distribution
Have limited neuroanatomical distributions and specific functions (sleep/wake cycle, hunger, stress response, emotional/cognitive role, social behavior)
Released from postsynaptic neuron and acts on PREsynaptic neuron to regulate NT release
Retrograde messengers
Some neuro chemicals mediate retrograde transmission this way
- synthesized and released by post neuron (non vesicular)
- bind specific receptors or other targets in PRE neuron
- regulate NT release, usually SUPPRESS release
Examples of retrograde messengers
- endocannabinoids (brains own marijuana)
- NO
- CO
What are the two precursor molecules for Ach?
Choline
Acetyl Co-A
Where do you get choline
Both dietary and recycled
Where do you get acetyl Co-A
Mitochondria
What breaks down Ach
Acetylcholinesterase
ChAT
Choline acetyltransferase
Choline deficiency
If poor nutrition, critical to brain development especially for mother and fetus
What all pathways in the brain use Ach?
A LOT
-Cranial motor nuclei III and X
In CNS, neurons located in
Forebrain and midbrain regions
Functional significant of neurons located in forebrain and midbrain regions
- regulates cognitive functions
- reward seeking behavior
- arousal/alertness/consciousness
- sleep cycle
Major excitatory NT in the CNS, especially in projection neurons. Ubiquitous (potent)
L-glutamate
Functional significance of L-glutamate
- involved in virtually all functions
- neuronal plasticity
- learning/memory
Glutamate excitotoxcicity
Mechanism implicated in a range of neurodegenerative disorders, stroke, traumatic brain injury
What are the primary sources of glutamate
2 from mitochondria
1 from astrocytes
What kind of receptors does L-glutamate use
Ionotropic
- AMPA or kainate
- NMDA
What kind of receptors are AMPA, kainate, and NMD?
Ionotropic
AMPA
- ionotropic
- ligand gated
- Na+, K+
- L glutamate
Kainate
- ionotropic receptor
- ligand gated
- Na+ K+
- L-glutamate
NMDA
- ionotropic
- ligand gates
- Na+, K+, Ca2+
- L glutamate
Key role in regulating neuronal excitability, morphological plasticity, and learning/memory
AMPA glutamate receptors
Key mechanism for regulating neuronal excitability and synaptic plasticity-critical for learning and memory
Receptor trafficking to and from post synaptic membrane
________ influx promote insertion of MORE AMPA receptors
EPSPs and Ca++
_______ can induce removal AMPA receptors, creating silent synapses
Lack of stimulation or IPSPs
Changes to neuronal excitability
Tend to be long lasting and slow to reverse
Role of NMDA receptor
Amplifier of excitation
Roles of NMDA as Ca++ channel
Amplifies depolarization
Key for synaptic plasticity
Receptor mechanism of NMDA receptor
- voltage gated and ligand gated
- at resting potential: Mg++ block
- depolarization releases Mg++ block and allows Ca++ influx as well as Na+/K+
Abused drugs that are NMDA antagonists
PCP
Ketamine
Over activation of NMDA receptor
Can be toxic!
Too much intracellular Ca++
Overactive glutamate and calcium can lead to what
Deficient synaptic clearance, necrosis, apoptosis
