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Lecture 19

BIO304H5 Lecture Notes - Lecture 19: Glycinergic, Function Type, Ligand-Gated Ion Channel

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Adriano Senatore

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April 3rd 2019
BIO304 Lecture 19
Neurotransmitters & Synaptic Transmission
Nervous system - basically coherent connection of cells integrated
Cells coordinate and give rise to properties to allow communication
Rapid communication - action potentials - needed for communication with mdiff
parts of body
Cells can’t only talk in fast ways because the consequences would be lost
because communication is lost
Cells communicate through different temporal scales - there are slower forms of
cellular communication that can last from minutes to hours - need of food, need
to hunt, etc.
Faster communication is for immediate body function
Neurotransmitters: a useful framework for reducing anatomical complexity in the CNS
Neurons use transmitters based on function - type of transmitters helps
understand where what is happening
We described how "marker" genes can be used to delineate neuron types
“Marker” genes are only expressed in cells of interest
These genes show where the neurotransmitter is expressed
Detecting mRNAs in tissues = in situ hybridization
Detecting proteins in situ = immuno-labelling
Pre-synaptic marker genes for neurotransmitter biosynthesis, degradation &
Postsynaptic marker genes for ionotropic & metabotropic receptors
provide deeper information, beyond strictly anatomical connectivity
e.g. Mapping glutamatergic (L-glutamate) and cholinergic (ACh) neurons
tells us about excitatory circuits in the nervous system
e.g. Mapping GABAergic (GABA) and glycinergic(glycine) neurons tells us
about inhibitory circuits in the nervous system
The Allan Mouse Brain Atlas
Took mice, sectioned their brains and used in situ hybridization to see
where gene is expressed
Sectioned the mice brain cross section
Comprehensive in situ hybridization of mRNAs in the sectioned mouse
e.g. vesicular glutamate transporter (Slc17) delineates
glutamatergic neurons
You know where gene will be expressed
Marker of glutamatergic neurons - regions of mouse brain and you can
see where the gene is expressed
Can pull up website where you can see cross section of brain and find

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April 3rd 2019
Major Transmitter Systems of the Brain - look at where the neurons on based on the mouse
brain atlas and see what each neurotransmitter does in brain
Acetylcholine-based synaptic transmission
In vertebrate neuromuscular junctions, acetylcholine (ACh) generates
post-synaptic depolarization in muscle fibers
Tells us where and when muscles contract
Activates pentameric ionotropic cys-loop channels
Dubbed nicotinic AChR’s (nAChRs) because they can be
activated by nicotine
Compound nicotine indirectly activates these channels
Non-selective with slight preference for Na+over K+
Equally roughly selective for Na and K
Slightly selective of Na at RMP
In the CNS, ACh also activates Cys-loop channels, but these are made up of only
α and β subunits (no γ or δ subunits)
Also very abundant in the brain - in muscles it is only alpha and beta
Various genes encode for neuronal nAChR α and β subunits
α2 to α7, β2 to β4 → do not need to memorize*
Varying α-β stoichiometry causes differences in ACh sensitivity and ion
Neurons that synthesize and secrete acetylcholine (i.e. cholinergic neurons) are
abundant throughout the vertebrate brain
Cholinergic neuron gene marker → choline acetyltransferase or ChAT
Abundant throughout the brain
2 little lips - expressions which are conserved in the human brain
The marker gene is enzyme called choline acetyltransferase that
synthesizes ACh - very important
Acetyl coA is taken and coupled with choline acetyltransferase
which synthesizes ACh
Septal nucleus that contain ACh - sends axons throughout the
hippocampus and rest of brain
Most cholinergic axon terminals in the CNS do not secrete ACh into
synaptic clefts
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