Nens220 lecture 6 interneuronal communication
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Nens220, Lecture 6 Interneuronal communication. John Huguenard. Electrochemical signaling. Synaptic Mechanisms. Ca 2+ dependent release of neurotransmitter Normally dependent on AP invasion of synaptic terminal Probabilistic. Probabilistic release. Synaptic release is unreliable

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Nens220, Lecture 6 Interneuronal communication

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Nens220 lecture 6 interneuronal communication

Nens220, Lecture 6 Interneuronal communication

John Huguenard


Electrochemical signaling

Electrochemical signaling


Synaptic mechanisms

Synaptic Mechanisms

  • Ca2+ dependent release of neurotransmitter

    • Normally dependent on AP invasion of synaptic terminal

  • Probabilistic


Probabilistic release

Probabilistic release

  • Synaptic release is unreliable

    • Action potential invasion does not necessary evoke release

    • Net response is product of number of terminals (or release sites, n ), size of unitary response (q), and probability (p) of release at each terminal

    • N varies between 1 and 100

    • p between 0 and 1

    • q is typically on the order of 0.1 to 1 nS


Binomial probability

Binomial probability


Postsynaptic properties ionotropic receptors

Postsynaptic properties: ionotropic receptors

  • Ligand gated receptors

  • Directly gated by neurotransmitter – ion pores

  • Can be modeled analogously to voltage-gated channels


The probability of a ligand gated channel be open p s will depend on

The probability of a ligand gated channel be open (Ps) will depend on:

  • on and off rates for the channel

  • With the on rate dependent on neurotransmitter concentration

  • This can be approximated by a brief (e.g. 1ms) increase, followed by an instantaneous return to baseline


Three major classes of ligand gated conductances ligands

Three major classes of ligand gated conductances: ligands

  • Excitatory

    • Glutamate

      • AMPA/Kainate receptors (fast)

      • NMDA receptors (slow)

  • Inhibitory

    • Gamma amino butyric acid GABAA receptors


Ampa glutamate

AMPA (glutamate)

  • Fast EPSP signaling

  • trise < 1ms

  • tdecay : 1..10 ms

  • Cation dependent

  • EAMPA 0 mV.


Ca 2 permeability ampar

Ca2+ permeability: AMPAR

  • Depends on molecular composition

  • GluR2 containing receptors are Ca2+ impermeable

    • Unless unedited

  • Prominent in principle cell (e.g. cortical pyramidal neuron) synapses

  • GluR1,3,4 calcium permeable

    • Calcium permeable AMPA receptors more common in interneurons


Ampar have significant desensitization

AMPAR have significant desensitization

  • Contributes to rapid EPSC decay at some synapses


Spike psp interactions

Spike/PSP interactions

Hausser et al.

Science Vol. 291. 138 - 141


Epsc ap coupling

EPSC/AP coupling

Galaretta and Hestrin

Science 292, 2295 (2001);


Epsp spike coupling ii

EPSP/spike coupling II

Galaretta and Hestrin

Science 292, 2295 (2001);


Nmda glutamate

NMDA (glutamate)

  • EPSP signaling, slower than with AMPA

    • trise : 2-50 ms

    • tdecay : 50-300 ms

  • cation dependent

  • ENMDA 0 mV

  • Significant Ca2+ permeability

  • NMDAR - necessary for many forms of long-term plasticity


Ndmar blocked by physiological levels of mg 2 o

NDMAR Blocked by physiological levels of [Mg2+]o

  • Voltage and [Mg2+]o dependent

  • Depolarization relieves block


Kainate receptors glutamate

Kainate receptors (glutamate)

  • Roles are less well defined than AMPA/NMDA


Inhibitory ligand gated conductances

Inhibitory ligand gated conductances

  • GABAA

    • Fast IPSP signaling

    • trise < 1ms

    • tdecay : 1.. 200 ms !, modulable

    • Cl- dependent

    • EGABAA range: –45 .. –90 mV

    • Highly dependent on [Cl-]i

      • Which is in turn activity dependent

      • NEURON can track this


Metabotropic receptors

Metabotropic receptors

  • Many classes

  • Conventional neurotransmitters, GABA, glutamate

  • Peptide neurotransmitters, e.g. NPY, opioids, SST

  • Often activate GIRKS

    • G-protein activated, inwardly-rectifying K+ channels


Mreceptors cont d

mReceptors, cont’d.

  • Inhibitory, hyperpolarizing responses.

  • Can be excitatory,

  • e.g. Substance P closes GIRKS

  • Slow time course

    • e.g. GABAB responses can peak in > 30 ms and last 100s of ms

  • Presynaptic & negatively coupled to GPCRs


Electrotonic synapses

Electrotonic synapses

  • Transmembrane pores

  • Resistive connection between the intracellular compartments of adjacent neurons

  • Prominent in some inhibitory networks


Perisynaptic considerations

Perisynaptic considerations

  • Neurotransmitter uptake by glia or neurons

  • Diffusion

  • heterosynaptic effects

  • extrasynaptic receptors

  • Hydrolysis


Presynaptic receptor mediated alterations

Presynaptic receptor mediated alterations

  • Mainly metabotropic

    • An exception is nicotinic AchR

  • Homosynaptic “autoreceptors”

  • Heterosynaptic receptors


  • Short term plasticity

    Short term plasticity

    • Dynamic changes in release probability

      • Likely mechanisms

        • Ca2+ accumulation in synaptic terminals

        • Altered vesicle availability

      • To implement

        • update Prel upon occurrence of a spike

        • then continue to calculate state of Prel dependent on P0 (resting probability) and tP(rel)


    Nens220 lecture 6 interneuronal communication

    250 pA

    2.5 ms

    250 pA

    Fran Shen


    Nens220 lecture 6 interneuronal communication

    Dynamic-Clamp: Artificial Autaptic IPSCs

    Based on Fuhrmann, et al. J Neurophysiol

    87: 140–148, 2002


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