Lecture 10-11 — Synaptic Transmission

EPSP

• Depolarizing synaptic potential

• Excitatory postsynaptic potential

IPSP

• Hyperpolarizing synaptic potential

• Inhibitory postsynaptic potential

EPSP + IPSP

• @ axon hillock

• Determines if the threshold potential is exceeded and an AP is stimulated

Classic neurotransmitters

• We’ve known for years

  • Acetylcholine

  • Amino Acids

  • Amines

Novel neurotransmitters

• Recognized in the past 25+ years

  • Peptides

  • Purines

  • Gasses

  • Lipids

Acetylcholine

• Neurotransmitter at cholinergic synapse

• Used by spinal motorneurons

• Every pathway of the autonomic nervous system

• Used diffusely throughout CNS as neuromodulator

ACh receptors

• Receptor channels (nicotinic receptor)

• GPCR (muscarinic receptor)

Nicotinic receptor

• Ligand gated ion channels

• Neurotransmitter binds and activates

• Permeable to Na+ — little to K+

• Causes depolarization of MP in postsynaptic cell

• ~2ms synaptic delay

• EPSP

Muscarinic receptor

• GPCR

• Protein kinase

• K+ leakage channels close when phosphorylated

  • Increase in MP

• ~20 second synaptic delay

Neuromodulation

• Ligand gated

• Drive or inhibit electrical activity

• Directly stimulates AP in cells

• GPCR — not ligand gated

• Effects are more subtle

Binding of ACh to receptor channel causes

• Opening of ion channels

• Entry of Na+, Exit of K+

• Movement of +ve charge into cell — depolarization

• EPSP

• FAST

Binding of ACh to GPCR causes

• Generation of second messengers

• Activation of kinases

• Phosphorylation of proteins in the postsynaptic membrane

• Some of the proteins that get phosphorylated are phosphorylation gated ion channels

• Phosphorylation gates K+ leakage channels closed

• SLOW

• Lasts minutes to hours

• EPSP

Glutamate

• Main excitatory neurotransmitter used throughout the CNS

• Receptor channels:

  • NMDA receptor

  • AMPA receptor

• GPCR

AMPA

• Will bind glutamate

• Receptor channels close opens

• Na+ ions pass into cell — EPSP — depolarization

NMDA

• Allows Na+ and Ca++ to pass

• Don’t open at RMP

• Blocked by Mg++ ions

• If MP gets depolarized then channel will open

GABA A

• Ionotropic

• Cl- ions pass into the cell

• ~2ms synaptic delay

• IPSP

• inhibitory in adult neurons

GABA B

• GPCR

• Varies in effect, depends on channels phosphorylated

• metabotropic

Binding of GABA or GABA(A) receptor channels close causes

• Opening of channel

• Cl- allows to enter the cells

• Hyperpoalrization

• IPSP — inhibitory

• FAST

Electrical synapses

• Fast and simple architecture

Chemical synapses

• Relatively complex, slower

• Electrical signal from one neuron is converted to a chemical signal

• Chemical signal crosses synaptic cleft, then causes an electrical signal in postsynaptic cell

• Allows excitatory → inhibitory

• Allows modulation

• Efficient

• Wide variety of receptors

How do Chemical synapses allow modulation of signals?

• A train of pre-syn action potentials does not necessarily result in a train of post-syn AP

• Complex information processing

How do chemical synapses become efficient?

• A few molecules of neurotransmitter can have a large electrical effect

Factors the play important roles in how synaptic information will add up in a network of neurons

• AP frequency

• Divergence and convergence

• Temporal and spatial summation

• Location of synapses on postsynaptic cell

Axodendritic

• On the dendrites

Axosomatic

• Closer than the synapse on dendrite

• Larger impact on threshold for AP

• A junction where the axon of one neuron connects directly to the cell body

Axoaxonic

• Usually on the axon hillock

• MOST powerful

• Decides whether or not there is AP

Axoaxonic (on a synaptic terminal)

• Occurs on the presynaptic terminals

• Can cause pre-synaptic facilitation or inhibition

• Facilitates more neurotransmitters

• Does not influence AP

• Only influences how many neurotransmitters

Divergent pathway of neurons

• One synaptic neuron branches to affect a larger number of postsynaptic neurons

Convergent pathway of neurons

• Many pre-synaptic neurons provide input to influence a smaller number of postsynaptic neurons

Temporal summation

• Occurs when two graded potentials form one presynaptic neurons occur close together in time

Spatial summation

• Occurs when the currents from nearly simultaneous graded potentials combine

Potentiation

• Synapses can get stronger

Long-term potentiation (LTP)

• Long lasting increase in amplitude of depolarization caused by a single presynaptic AP

• Requires NMDA & AMPA

• Metabotropic glutamate receptors also play a role

• Rise in intracellular Ca++ in crucial

• Pre and post synaptic changes