Download Computational Neuroscience Models of Synaptic Transmission and

Computational Neuroscience
2036FBDBMW
Master of Science in Computer Science (Scientific Computing) Master of Science in Biomedical Sciences (Neurosciences)
Master of Science in Physics
Prof. Dr. Michele GIUGLIANO
Models of Synaptic
Transmission and Plasticity
Computational Neuroscience
Electrical synaptic transmission
(bidirectional, slow, without “sign”)
Electrical synaptic transmission
(bidirectional, slow, without “sign”)
Electrical synaptic transmission
(bidirectional, slow, without “sign”)
Isyn = ggap (Vpre
Vpost )
Electrical synaptic transmission
(bidirectional, slow, without “sign”)
Cali’ et al. (2007)
Chemical synaptic transmission
(unidirectional, fast, with “sign”)
National Institute on Aging / National Institutes of Health
Simultaneous whole-cell patch-clamp recordings
from several neurons simultaneously
Song et al. (2005)
Synaptic receptors
(located on the membrane of the postsynaptic - i.e. target - neuron)
Ionotropic receptors
(i.e. pore)
Metabotropic receptors
(i.e. no pore exists!)
EPSCs - excitatory postsynaptic currents
EPSPs - excitatory postsynaptic potentials
IPSCs - inhibitory postsynaptic currents
IPSPs - inhibitory postsynaptic potentials
Excitatory Synaptic receptors
mediated by/permeable to Na+ and/or Ca++
Mediated by
“fast-activating” receptors
receptors are ligand-gated
ion channels
(i.e. ionotropic receptors)
AMPAr
NMDAr
ACh r
Esyn =
Mediated by
“slow-activating” receptors
receptors are ligand-activated
protein that trigger an intracellular
cascade of reactions leading to
(intracellular-side) gating of
channels
(i.e. metabotropic receptors)
K T
log
zq
✓
mGLUr
Cout
Cin
◆
> Vrest
Inhibitory Synaptic receptors
mediated by/permeable to K+ or ClMediated by
“fast-activating” receptors
receptors are ligand-gated
ion channels
(i.e. ionotropic receptors)
GABA-A r
Gly r
Esyn
Mediated by
“slow-activating” receptors
receptors are ligand-activated
protein that trigger an intracellular
cascade of reactions leading to
(intracellular-side) gating of
channels
(i.e. metabotropic receptors)
K T
=
log
zq
✓
GABA-B r
Cout
Cin
◆
< Vrest
December 12th, 2012: 14:00 -­‐ 17:00
January 9th, 2013: 14:00 -­‐ 17:00
January 31st, 2013: 09:00 -­‐ 11:00 (oral presenta>on of the miniprojects)
February 6th, 2013: 09:00 -­‐ 12:00 (oral exam)
Chemical synaptic transmission
(unidirectional, fast, with “sign”)
Isyn = gsyn (t) (Esyn
gN a
gK
gCl
gleak
from Sterratt et al., 2011
Vm )
Chemical synaptic transmission
(unirectional, fast, with “sign”)
model of a ionotropic receptor
dO(t)
=
dt
O + ↵ [T ] C
dC(t)
= + O
dt
↵ [T ] C
O(t) + C(t) = 1
Destexhe et al. (1994)
dO
O1
O
=
dt
⌧O
O1 =
↵ T (t)
↵ T (t) +
⌧O =
1
↵ T (t) +
from Sterratt et al., 2011
Destexhe et al. (1994)
Isyn = ḡsyn O(t) (Esyn
Vm )
from Sterratt et al., 2011
NMDAr: Ligand- and voltage-dependent synaptic currents
(this has the potential for pre/post coincidence-detection)
IN M DAR = GN M DAR r(t) (EN M DAr
GN M DAR = GN M DAR (V, [M g 2+ ])
Vm )
Chemical synaptic transmission
model of a metabotropic receptor
Isyn = ḡsyn O(t) (Esyn
Vm )
Chemical synaptic transmission
simplified model of ionotropic receptor (population)
dO(t)
dO
=
=
dtdt
dO
⇡
dt
O +
+ ↵↵ T[T
] C
O
(1
max
O)
X
(t
tk )
k
O + ↵ Tmax
X
(t
tk )
k
+
O(t+
k+1 ) ⇡ O(tk )e
(tk+1 tk )
OSS ⇡ ↵ Tmax
1
f
+ ↵ Tmax
Chemical synaptic transmission
simplified model
OSS ⇡ ↵ Tmax
f
1
f
output
synapse
analog variable
propor1onal to
the driving frequency
(current or conductance)
neuron
f
Synaptic connections are more than connecting plugs
They are physical systems
implementing a dynamical
communication channel...
Like all physical system they may show
(transient) inertia, fatigue, or
depression during repeated activation.
They may also, on the contrary,
(transiently) warm up upon use
and facilitate further communications.
Short-term (homosynaptic) plasticity.
(neuromuscular junction, central syn.)
National Institute on Aging / National Institutes of Health
depressing
EPSPs
facilitating
EPSPs
spike train
Short-term plasticity: facilitation and depression
(cortical pyramidal neurons)
Wang et al. (2006)
Tsodyks & Markram(1997)
Short-term plasticity: facilitation and depression
Markram et al. (1998)
Short-term plasticity: facilitation and depression
(olfactory bulb, mitral cells, same glomerulus)
Pignatelli et al., submitted
Impact of short-term synaptic plasticity
Markram et al. (1998)
Impact of short-term synaptic plasticity
27
Markram et al. (1998)
Modeling short-term synaptic plasticity
(Pre)synaptic
resources
(e.g., vesicles)
Modeling short-term synaptic plasticity (depression)
Modeling short-term synaptic depression
30
Modeling short-term synaptic depression
31
≃
≃
≃
≃
≃
Modeling short-term synaptic depression
≃
34
Markram et al. (1998)