Chapter 6: synaptic transmission II: neurotransmitter systems
Types of neurotransmitters
cholinergic: neurons and synapses that produce and release acetylcholine
noradrenergic: neurons that use norepinephrine
Criteria that define a neurotransmitter
molecule must be SYNTHESIZED/STORED in PRESYNAPTIC NEURON
molecule must be RELEASED by PRESYNAPTIC axon terminal
molecule, when experimentally applied, must mimic POSTSYNAPTIC EFFECT of PRESYNAPTIC stimulation
chAT: manufactured in soma, transported to terminal
vesicular ACh transporter: transports Ach into vesicle
AChE: manufactured by the cholinergic neuron, secreted into synaptic cleft
Choline transporter: transports choline into the terminal
glutamatergic receptors (inotropic): AMPA, NMDA, Kainate
coexistence of NMDA and AMPA receptors in postsynaptic membrane
AMPA: Na+, K+
NMDA: Na+, K+, Ca++
NMDA receptor is BOTH a ligand and voltage-gated ion channel
ligand gate: glutamate must be bound
Voltage gate: at resting Vm, channel is blocked by Mg++
Mg++ block is removed by DEPOLARIZATION
AMPA receptor channels mediate initial depolarization
that's why NMDA and AMPA receptors coexist
NMDA receptor is a coincidence detector
channels opens only when BOTH pre and post synaptic elements are active
presynaptic cell is active: it's releasing glutamate
postsynaptic cell is active: it's depolarized (by AMPA receptors) and Mg++ block is removed
Na+ and Ca++ enters postsynaptic cell
increased intracellular Ca++ initiates cascade of events
activates enzymes
regulates opening of ion channels
affect gene expression
increased synaptic strength for memory and learning
4 neurotransmitters use METABOTROPIC and IONOTROPIC receptors
ACh
amino acids: glutamate, GABA, Glycine
GPCR: longer lasting than inotropic receptors
a subunit binds GDP, complex stays together as an inactive trimer
When transmitter binds to GPCR, GTP replaces GDP, trimer splits apart into active a and By subunits
a and By subunits interact with ion channels or enzymes that activate 2nd messenger systems
hydrolysis of GTP by a subunits REASSEMBLES the inactive trimer
Direct action of G-protein - "shortcut pathway" (effector is an ion channel)
G proteins are activated by neurotransmitter binding to GPCR
activated By subunit DIRECTLY induces channel to open
Indirect action of G-protein (effector is enzyme)
neurotransmitter activates G-protein
2nd messenger starts cascades of events
activation of downstream enzyme - secondary chemical reactions
key downstream enzymes in many second messenger systems are protein kinases
protein kinases: phosphorylate proteins
protein phosphates: dephosphorylates proteins
Synaptic Integration
how do neurons operate in neuronal circuits?
sensory input --> CNS --> motor output
complicated input-output relationship
divergence: cells SEND inputs to a large number of other neurons
convergence: cells RECEIVE inputs from more than one cell
Central synapses
at the neuromuscular junction, an AP in presynaptic motor neuron leads to EPSP (end plate potential) in the muscle cells that is large enough for the muscle cell to reach threshold for an AP
In CNS, a single presynaptic neuron is UNLIKELY to excite postsynaptic cell
Summation
spatial summation: several SPATIALLY DISTINCT inputs fire SIMULTANEOUSLY
temporal summation: SEQUENTIAL firing
subthreshold signals DECAY with distance
Location of inhibitory inputs
presynaptic inhibition
decreases amount of depolarization in presynaptic terminal
specific, aimed at particular excitatory inputs
postsynaptic inhibition
affects all inputs (not specific)
Shunting inhibition
inhibitory synapse prevents current from reaching soma
depolarizing current LEAKS out before reaching soma