Computational Neuroscience. Models of Synaptic Transmission and Plasticity. Prof. Dr. Michele GIUGLIANO 2036FBDBMW

Transcription

1 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

2 Electrical synaptic transmission (bidirectional, slow, without sign ) Electrical synaptic transmission (bidirectional, slow, without sign )

3 Electrical synaptic transmission (bidirectional, slow, without sign ) I syn = g gap (V pre V post ) Electrical synaptic transmission (bidirectional, slow, without sign ) Cali et al. (2007)

4 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)

5 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

6 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 E syn = KT zq log 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) Cout C in mglur > V rest Inhibitory Synaptic receptors mediated by/permeable to K+ or Cl- Mediated by fast-activating receptors receptors are ligand-gated ion channels (i.e. ionotropic receptors) GABA-A r Gly r E syn = KT zq log 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) Cout C in GABA-B r < V rest

7 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 ) from Sterratt et al., 2011 I syn = g syn (t) (E syn V m ) g Na g K g Cl g leak

8 Chemical synaptic transmission (unirectional, fast, with sign ) model of a ionotropic receptor do(t) dt dc(t) dt = O + [T ] C = + O [T ] C O(t) + C(t) = 1 Destexhe et al. (1994) do dt = O 1 O O O 1 = O = T(t) T(t) + 1 T(t) + from Sterratt et al., 2011

9 I syn = ḡ syn O(t) (E syn V m ) Destexhe et al. (1994) from Sterratt et al., 2011 NMDAr: Ligand- and voltage-dependent synaptic currents (this has the potential for pre/post coincidence-detection) I NMDAR = G NMDAR r(t) (E NMDAr V m ) G NMDAR = G NMDAR (V,[Mg 2+ ])

10 Chemical synaptic transmission model of a metabotropic receptor I syn = ḡ syn O(t) (E syn V m ) Chemical synaptic transmission simplified model of ionotropic receptor (population) do(t) dt dt do dt = O + T [T max ] C(1 O) X (t t k ) k X O + T max (t t k ) O(t + k+1 ) O(t+ k )e (t k+1 t k ) + T max O SS T max 1 f k

11 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

12 spike train Short-term plasticity: facilitation and depression (cortical pyramidal neurons) facilitating EPSPs depressing EPSPs Wang et al. (2006) Tsodyks & Markram(1997) Short-term plasticity: facilitation and depression Markram et al. (1998)

13 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)

14 Impact of short-term synaptic plasticity 27 Markram et al. (1998) Modeling short-term synaptic plasticity (Pre)synaptic resources (e.g., vesicles)

15 Modeling short-term synaptic plasticity (depression) Modeling short-term synaptic depression 30

16 Modeling short-term synaptic depression 31

17 Modeling short-term synaptic depression 34 Markram et al. (1998)