Module 1: Synapses, plasticity and circuits The synapse: transfer of - - PowerPoint PPT Presentation

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Module 1: Synapses, plasticity and circuits The synapse: transfer of - - PowerPoint PPT Presentation

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Module 1: Synapses, plasticity and circuits The synapse: transfer of information 1 ms The synapse: transfer of information The synapse The miniature postsynaptic response (or mini) Fatt and Katz, 1952 - Remain in the presence of TTX -

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Module 1: Synapses, plasticity and circuits

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The synapse: transfer of information

1 ms

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The synapse: transfer of information

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The synapse

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Fatt and Katz, 1952

The miniature postsynaptic response (or ‘mini’)

  • Remain in the presence of TTX
  • Prolonged by blockers of acetylcholine esterase
  • Blocked by AChR antagonists
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Del Castillo and Katz, 1954

Quantal nature of neurotransmitter release

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Quantal nature of neurotransmitter release

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Quantal nature of neurotransmitter release

Heuser and Reese, 1981

Freeze fracture: vesicles caught in the act

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Distinct vesicle pools Rapidly releasable pool Reserve Pool Resting Pool

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The presynaptic vesicle cycle

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Calcium Dependence of Neurotransmitter release

4- No calcium 1- No calcium 2- A little calcium 3- A little more calcium Katz

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Caged-calcium experiments

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Schneggenberger and Neher, nature 2000

Dependence of Neurotransmitter release on [Ca2+]int

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Calcium nanodomains

Neher, CONB, 1998

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Postsynaptic structures

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Why spines?

1- Increase surface area to optimize packing of many synapses 2- Serve as a separate electrical unit that modulates synaptic signals 3- Provide a biochemical compartment that restricts mobility of molecules

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Postsynaptic structure

Spines: occur at around 1-10 per um of dendrite

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Synapse diversity: postsynaptic spine

Matsuzaki et al., 2001 Arellano et al., 2007

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Postsynaptic structure: spines

Nimchinsky et al., ARN, 2002

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Postsynaptic spine shape

Rneck = ⁄ "# $, where L is length of neck and A is cross-sectional area and " is resistivity of cytoplasm

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Spine neck can filter synaptic events

Araya et al., PNAS, 2006

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Noguchi et al., Neuron, 2005

Postsynaptic spine shape: calcium diffusion

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Molecular architecture of excitatory synapses

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Glutamate-gated channels

AMPAR NMDAR mGluRs

GluR1-4: Tetramers mostly of GluR2 and two others. Flip/flop: alternative splice variants Q/R editing: calcium permeability Almost all GluR2 subunits are in the R form, which is Ca2+ impermeable. GluN1-2: Tetramers of GluN1 (obligatory) and GluN2 A-D. Calcium permeable. Co-agonist: glycine. Blocked by Mg2+ at rest. 3 groups based on pharmacology Sequence and signalling. Group 1: mGlu1 and 5. Group 2: mGlu2 and 3. Group 3: mGlu4, 6, 7 and 8.

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AMPA and NMDA currents

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Na+ in K+ out

Normal situation recording Vm Inject current to depolarise to -20mV

Less Na+ in No ion movement

Inject more current

Na+ no mvt K+ out

Inject even more current ! No ion movement at the EPSP’s reversal potential

The EPSP: carried mainly by AMPA receptors

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Glutamate postsynaptic currents

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GABAA receptors

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Cl- in

Normal situation recording Vm

No ion movement

Inject hyperpolarising current

Cl- Out

Inject more negative current

The IPSP

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GABAB receptors

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Plasticity of synapses and transmission: mechanisms

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Short Term Plasticity: heterogeneous responses to spike trains

Same presynaptic neuron, different targets

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Different presynaptic neurons, same target

Short Term Plasticity: heterogeneous responses to spike trains

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Mechanisms: Possible Sites for Modulation

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Width of an Action Potential

Geiger and Jonas, Neuron, 2000

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Types of short-term plasticity

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Facilitation at Granule to Purkinje Synapse

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Facilitation and Residual Calcium

Could use slow buffer (eg: EGTA) to ‘mop up’ residual calcium

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Facilitation and Residual Calcium

Alturi and Regehr, J. Neurosci., 1996

Process: high affinity, slow off rate

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Plasticity of synapses and transmission: mechanisms and functional relevance

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Carew and Kandel, 1973

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Carew and Kandel, 1973

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Bliss and Lomo, 1973

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The Organisation of Behaviour (1949) When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.[3] This is often paraphrased as "Neurons that fire together wire together." It is commonly referred to as Hebb's Law.

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The Organisation of Behaviour (1949) When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.[3] This is often paraphrased as "Neurons that fire together wire together." It is commonly referred to as Hebb's Law.

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