Download Ionic mechanisms of communication

Signal processing in neurons
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Metabotropic neurotransmission
Electrical signals in dendrites
Active properties of dendrites
Signal processing at the
– Synapse (post)
– Dendrite
– Soma
– Synapse (pre)
Neuronal Anatomy
• Dendrites
– Input-spine
• Cell Body/Soma
• Axon
– Output-bouton
Neural circuits, cartoon version
• Spindle afferents excite the
homonymous motor neuron and inhibit
antagonists
MNa
IN
Inhibitory
synapse
Ia
MNb
Excitatory
synapse
Agonist
Antagonist
Dendrite Morphology
• Multiple synapses (10k+)
• Multiple morphologies
• Post-synaptic density
VI Popov et al., 2004 Neuroscience
Synaptic structure
Garner 2002
Input E/I PSPs
• Synaptic strength
– Efficiency of neurotransmitter release
– Area/receptor number
• Dendrite morphology
– Input resistance
– Membrane capacitance
NMDA receptor mediated plasticity
• Glutamineric synapses have both AMPA and NMDA
receptors
– Long term potentiation: Tetanus increases subsequent
EPSPs
– Tetanic depolarization relieves Mg2+ block (NMDA)
– Calcium induced channel phosphorylation increases
conductance
– Long term potentiation
• Ca2+ influx via NMDA receptors
• DepolNMDACa2+CaMKIIAMPA
• Ca2+(PKA)-|I1->PP1-|AMPA
Low frequency stimulation
Low Calcium
I1 activates PP1
Decreases AMPA
High frequency stimulation
High Calcium
I1 is inhibited
Reduces PP1
Increases AMPA
Metabotropic neurotransmission
• GPCRs
– Gs Adenyl Cyclase
• AC->PKA->channel phos (NaV)
– Gq phospholipase C
• PLC->DAG->PKC->channel phos (AMPA)
– Gbg GirK G-coupled inward rectifying
potassium channel
– Gbg CaV N, P, Q type voltage gated calcium
channel
• Slow – seconds to minutes
Girk
• Hippocampal neurons
• GABAA channel
Picrotoxin blocks GABAA
Ba2+ blocks K+
– 1300 pA Cl- current
• GABAB GPCR
– 50 pA K+ current
– Slow kinetics
– Different GABA
sensitivity
GABAA
GABAB
• Cooperative currents
different time Distinct I-V curves
Different reversal potentials
Sodickson & Bean 1996
Metabotropic Neuromodulation
• DSI stimulation triggers fast and slow
depolarization
– Slow depolarization is GTP dependent
– Blocked by non-exchangeable GDP-b-S
Fast Ionotropic
depolarization
Slow metabotropic
depolarization
Recording
Stimulation
Blocks metabotropic
process
mGluR1 suppression of m-current
• M-Current: potassium current, near
threshold, helps set excitability
• After-hyperpolarization
EPSPs recorded in CA3 neurons of guinnea pig
DHPG is an mGluR agonist
Brief exposure Long exposure
Prolonged exposure to
DHPG results in
sustained inactivation
of m-current
Sustained, but not
immediate
suppression requires
p38 MAP kinase
Young S R et al. J Neurophysiol 2008;99:1105-1118
Electrical interaction in dendrites
• Local depolarization propagates
– Internal resistance
– Membrane capacitance
– Time constants RC
• Signal attenuation
– Leak current
Extracellular
Rm
Intracellular
Cm Rm
Ri
Cm
Active properties of dendrites
• NaV
– Low density prevents AP
– PSP regeneration, amplification
• CaV
– T-type, low threshold
– “Window current” bistatility
– Additional calcium-mediated magic
• Ih
– Slow depolarization
– Pacemaker
Multiple inputs
• Consider Unitary PSP 5 mV
– Input current ~ 750pA = GV = G(0.060-(-0.060)
– G=6250 pS (multiple channels at one synapse)
• Simultaneous PSP
– G=12,100pS
– Input current 1500 pA
• Second PSP during coincident wave:
– G=6250; V=(0.06-(-0.055))= 115 mV
– Input current = 720 pA
• Dendritic branches isolate circuits
Coincidence reinforcement
• “Hebbian” plasticity
– Neurons that fire together, wire together
– Reinforcement of synapse consequent to AP
– Back-propagation of AP, faster than PSP
Stuart & Hauser, 2001
Current interactions
•Kleak
•KNa
•Ih (Nah)
•NMDA
•LVA (CaT)
•NaV
•HVA (CaL)
•Kir
•KCa
•Cl
• Multiple ions, multiple gatings
• Local to synapse or distributed
• Experimental models are incomplete:
– Intact, decerebrate, isolated spine, slice, culture
– Unique populations of neurons
• See Grillner (2003); construct potential in a
CPG or motor neuron w/nifedipine, stychnine, etc
Axon hillock
Integrates signals across dendritic tree
Dense NaV, highest probability of AP
Rheobase
5
Chronaxie
4
Stim Ampl (nA)
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Rheobase
No Action
Potential
Action
Potential
3
2x Rheobase
2
Chronaxie
1
0
0
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2
Stim Duration (ms)
Output Action Potential
• Presynaptic inhibition
– Ionotropic
• Sub threshold depolarization of bouton
• Reduce Ca2+ influx
– Metabotropic
• mGluR group II & IIII
• Local NT release feeds back on presynaptic
neruon
Sea slug (tritonia) locomotion
• Characteristic escape response
• Alternate, vigorous body flexion
• Simple neural circuit
Lawrence & Watson 2002
Tritonia CPG
• Escape is a programmed response
– Katz, et al., 2004
Flex
Extend
Ventral Flexion Neuron
Dorsal Swim Interneuron
Ventral Swim Interneuron
Stimulate sensory neurons to elicit escape
Intracellular potential
of neurons
Dorsal Flexion Neuron
Tritonia Metabotropic
Neuromodulation
• DSI stimulation triggers fast and slow
depolarization
– Slow depolarization is GTP dependent
– Blocked by non-exchangeable GDP-b-S
Fast Ionotropic
depolarization
Slow metabotropic
depolarization
Recording
Stimulation
Blocks metabotropic
process