Exam 2 (Lecture 12/13) Flashcards
Sympathetic
Fight or flight
Thoracolumbar
Parasympathetic
Rest and Digest
Craniosacral
Neuron
fundamental units of the nervous system for transforming and relaying the electrical signals
Astrocyte
provides biochemical support of endothelial cells that form the blood–brain barrier (BBB),
supplies nutrients to the nervous tissue
Oligodendrocyte
provides he axon of long-range projection neurons insulation by a myelin sheath
Vasculature
supplies oxygen and nutrients, the brain would quickly suffer damage from any stoppage
in blood supply
Myelin Sheath
insulates the projections of neurons and increases conductivities.
Schwann Cells found in
PNS
Oligodendrocytes found in
CNS
Blood Brain Barrier
functions as a border that prevents solutes in the circulating blood from non-selectively to avoid toxic substance coming in.
Soma
cell body; perikaryon
contains nucleus and most of cytoplasm
features of active secretory cell (large nucleus, lots of endoplasmic reticulum, prominent Golgi)
Dendrites
information “receiving” elements
fine processes extending from soma in tree-like arrangement;
can be many along with soma comprises receptive field of neuron
Axon
information “transmitting” element
a thin process extending from axon hillock (initial segment of axon as it leaves soma) along which action potential is conducted
one per neuron: can be long or short, single or branched, myelinated or not myelinated
Axon Terminal
(terminal boutons; presynaptic terminals)
swelling of axon at its terminal end, enriched with vesicles containing neurotransmitter
forms “synaptic contact” with receptive region of
a second neuron (i.e. a postsynaptic neuron)
swellings filled with vesicles can also occur along length of axon giving rise to a beaded appearance (these swellings are called varicosities); may form synapses
Basic Elements of chemical neurotransmission
- Arrival of action potential at axon terminal
- Depolarization of axon terminal membrane
- Influx of Ca++ into terminal via voltage-gated Ca++ channels
- Fusion of vesicles with terminal membrane
- Extrusion of vesicle contents into synapse: exocytosis
- Binding of transmitter to postsynaptic receptors
- Opening of chemically-gated ion channel
- Change in membrane potential
EPSP if Na+ Channels open (depolarization)
IPSP if K+ or Cl- channels open (hyperpolarization) - Termination of transmitter action by re-uptake into presynaptic terminal, or by enzymatic degradation, or both
Criteria for Neurotransmitter
- Substance must be present in presynaptic neuron and its terminals (precursors and synthetic enzymes should also be present)
- Substance must be released from presynaptic terminals with neuronal activity
- Effects of the applied substance on a target neuron (postsynaptic cell) must be same as effects of stimulating the presynaptic neuron
- antagonist of the substance should also block both - Mechanism for the transmitter candidate’s inactivation must be present in the synapse
SNARE Cycle
- Synaptobrevin interacts with two plasma membrane target proteins, the transmembrane protein syntaxin and the peripheral membrane protein SNAP-25.
- The three proteins form a tight complex bringing the vesicle and presynaptic membranes in close apposition (see part B). Munc18 binds to the SNARE complex.
- Calcium influx triggers rapid fusion of the vesicle and plasma membranes; the SNARE complex now resides in the plasma membrane.
- Two proteins, NSF and SNAP (unrelated to SNAP-25), bind to the SNARE complex and cause it to dissociate in an ATP-dependent reaction.
Neurotransmitter structures
Amines Purines Monoamines Amino Acids Endocannabinoids Peptides
Linked to cationic channels (excitatory)
Glutamate
Aspartate
Linked to anionic channels (inhibitory)
GABA
Glycine
Glycine
• Receptor antagonist: strychnine
• Mechanism of action: similar to GABA (i.e.
increases Cl- conductance)
• Major inhibitory transmitter in spinal cord
γ-Aminobutryic acid (GABA) cycle
- Reuptake (GAT1)
- Transport into glial cells (GAT3)
- Conversion to glutamine (GS)
- Transport into GABAergic neuron (SAT)
- Package into vesicles (VGAT)
Glutamic acid (glutamate) cycle
- Reuptake (GLT)
- Transport into glial cells (GLT/GLAST)
- Conversion to glutamine (GS)
- Transport into GABAergic neuron (SAT)
- Package into vesicles (VGLUT)
Glutamate synthesis
a dietary amino acid, also synthesized in neurons from precursor glutamine
Glutamate receptor subtypes
NMDA, AMPA, Kainate = ligand-gated
mGLuR 1-8 = metabotropic
Glutamate receptor angonists
monosodium glutamate (MSG, food additive, flavor enhancer) Kainic acid (potent neurotoxin, excites neurons to death)
Glutamate mechanism of action
increases in membrane cation (Na+ and Ca++) permeability thereby depolarizing neuronal membrane
LTP
Long Term potentiation
Increase AMPA
Synaptic strengthening
Post synaptic end senses Glutamate, increases receptors to adjust, they stay for a period
LTD
Long term depression
Synaptic weakening
decreasing AMPA
receptors get internalized, fewer at surface
Acetylcholine (ACh) synthesis
Choline + Acetyl Coenzyme A = Acetylcholine + Coenzyme A via Choline acetyltransferase
ACh inactivation
Acetyle Choline = Choline + Acetate via acetylcholinesterase
2 Classes Cholinesterase enzymes
acetylcholinesterase “true” - neural tissue, in synaptic cleft
Butyrlcholinesterase “pseudo” - plasma, liver
ACh receptors
Nicotinic = ligand-gated ion channel, agonist is nicotine
Muscarinic = g-protein coupled M1-M5 subtypes, agonist is muscarine
ACh cycle
- Degradation (AChE)
- Transport into presynaptic site (CHT)
- Conversion to ACh (ChAT)
- Package into vesicles (VAChT)
Catecholamine synthesis
Tyrosine -> Dopa via Tyrosine Hydroxylase (TH)
Dopa -> Dopamine via AADC (or DOPA decarboxylase)
Dopamine -> Norepinephrine vis DBH
Norepinephrine -> Epinephrine via PNMT
Catecholamine inactivation
- Re-uptake = Rapid (blocked by cocaine and tricyclic antidepressants
- Enzymatic Degradation = slower 2 enzymes
MAO and COMT
MAO
Monoamine oxidase
blocked by drugs known as MAO inhibitors
primarily intraneuronal, cytoplasm of nerve terminal
COMT
Catechol-o-methyltransferase
Extraneuronal metabolism
Catecholamine Cycle
Reuptake (DAT/NET)
Package into vesicles (VMAT2)
dopamine receptors
All G-protein coupled, D1-D5
Norepinephrine receptors
two families, designated α and β, all G- protein coupled
Serotonin (5-HT) synthesis
Tryptophan -> 5-hydroxytryptophan via TPH
5-hydroxytryptophan - > Serotonin via AADC
Serotonin cycle
Reuptake (SERT)
Package into vesicles (VMAT2)
Serotonin receptors
5HT3 - ligand-gated ion
All others are G-protein
Histamine Synthesis
Histidine -> Histamine via Histidine Decarboxylase
Histamine Metabolism
histamine N-methyltransferase
Glutamate apoptosis (Excitotoxicity
All signaling activated by calcium, leading to cell death
Ultra Short neurons
retina and olfactory bulb neurons
Intermediate length neurons
Hypothalamus to pituitary (mediate endocrine functions)
dopaminergic pathways
A9, motor functions, substantia nigra pars compact to striatum
A10, mediate pleasure and reward, Ventral Tegmental area to limbic areas of brain
Norepinephrine pathways
A1,A2,A5,A7
Serotonergic pathway
begins Raphe nuclei
H1 receptor
antihistamine target
H2 receptor
Gastric acid secretion target
Peptide transmitters
mRNA -> rough ER to make -> Golgi to pack -> move to synapse via large dense-core vesicles -> no reuptake, catabolic peptidases turn into inactive metabolite once released in synapse.
Need more control/ high frequency for release not CA like other neurotransmitters.
GABA A/C
ionotropic receptor - fast
GABA B
G protein receptor
Cholinergic Pathways
Originate in Nucleus Basalis of Meynert
Where do Norepinephrine neurons originate?
Locus Ceruleus
