Post on 13-Jan-2016
description
funding: U.S. National Science Foundation
Rhythms in central pattern generators – implications of escape and release
Jonathan RubinDepartment of Mathematics
University of Pittsburgh
Linking neural dynamics and codingBIRS – October 5, 2010
goal: to understand the mechanisms of rhythm generation, and modulation, in the mammalian brainstem respiratory network and other central pattern generators (CPGs)
•Brief introduction to CPGs•Transition mechanisms in pairs with reciprocal inhibition
-- escape/release -- changes in drives to single component
• Applications of ideas to larger networks
Talk Outline
examples of central pattern generators
crustacean STG – Rabbeh and Nadim, J. Neurophysiol., 2007
leech heart IN network – Cymbalyuk et al., J. Neurosci., 2002
overall, central pattern generators (CPGs)
• exhibit rhythms featuring ordered, alternating phases of synchronized activity
+
=
group 1
group 2
CPG rhythm
• rhythms are intrinsically produced by the network
• rhythms can be modulated by external signals (CPG output encodes environmental conditions)
Nat. Rev. Neurosci., 2005
Pace et al., Eur. J. Neurosci., 2007: preBötzinger Complex (mammalian respiratory brainstem)
starting point for modeling CPG rhythms: eliminate spikes!
half-center oscillator (Brown, 1911): components not intrinsically rhythmic; generates rhythmic activity without rhythmic drive
reciprocal inhibition
−
−
time courses for half-center oscillations from 3 mechanisms: persistent sodium, post-inhibitory rebound (T-current), adaptation (Ca/K-Ca)
simulation results: unequal constant drives
intermediate
adaptation
persistent sodium
post-inhibitory rebound
relative silent phase duration for cell with varied drive
relative silent phase duration for cell with fixed drive
Daun et al., J. Comp. Neurosci., 2009
fixed varied−
−
Why? transition mechanisms: escape vs. release
Wang & Rinzel, Neural Comp., 1992; Skinner et al., Biol. Cyb., 1994
inhibition on
inhibition off
inhibition on
inhibition off
fast fast
slow
example: persistent sodium current w/escape
fast
slow
Daun, Rubin, and Rybak, JCNS, 2009V
short silent phase for cell w/extra drive
baseline drive
inhibition off
extra drive
baseline orbitinhibition on
persistent sodium w/ unequal drives
baseline extra drive
−
−
fast
slow
V
Daun, Rubin, and Rybak, JCNS, 2009
Summary
• escape: independent phase modulation (e.g., persistent sodium current)
• release: poor phase modulation (e.g., post-inhibitory rebound)
• adaptation = mix of release and escape: phase modulation by NOT independent (e.g., Ca/K-Ca currents)
Daun et al., JCNS, 2009
applications to respiratory model (1)
Smith et al., J. Neurophysiol., 2007I-to-E E-to-I
inhibition excitation
1
23
4
12
4
3
baseline 3-phase rhythm: slow projection
I-to-E transition forced to be by release: cell 2 releases cells 3 & 4
E-to-I transition by escape: cells 1 & 2 escape to start I phase
main predictions (T = duration):
• increase D1, D2 decrease TE , little ΔTI
• increase D3 little ΔTI, ΔTE
(expiratory adaptation)
(inspiratory adaptation)
E
I
4
3 2
1
Rubin et al., J. Neurophysiol., 2009
predictions:
increase D1, D2 decrease TE, little ΔTI
increase D3 little ΔTI, ΔTE
Rubin et al., J. Neurophysiol., 2009
applications to respiratory model (2): include RTN/pFRG, possible source of active expiration
basic rhythm lacks late-E (RTN/pFRG) activity
Rubin et al., J. Comp. Neurosci., 2010
hypercapnia (high CO2 ):
• model as increase in drive to late-E neuron
• late-E oscillations emerge quantally
• I period does not change
Why is the period invariant? Phase plane for early-I (cell 2):
synapses on synapses ½-max
read off m2 values
trajectories live here!
repeat for different input levels
synapses on synapses ½-max
inhibited
excited
even with late-E activation, early-I activates by escape - starts inhibiting expiratory cells while they
are fully active (full inhibition to early-I and late-E)
Why is the period invariant?
thus, late-E activation has no impact on period!
(similar result if pre-I escapes and recruits early-I)
excitation
inhibition
applications (3) – limbed locomotion model
Markin et al., Ann. NY Acad. Sci., 2009
Spardy et al., SFN, 2010
CPG(RGs, INs)
motoneurons
muscles + pendulum
drive
locomotion with feedback – asymmetric phase modulation under variation of drive
does this asymmetry imply asymmetry of CPG?
Markin et al., SFN, 2009
locomotion with feedback – asymmetric phase modulation under variation of drive
locomotion without feedback – loss of asymmetry
drive
drive
no! – model has symmetric CPG yet still gives asymmetry if feedback is present
rhythm with/without feedback: what is the difference?
with feedback
IN escape controls phase transitions
Lucy Spardy
without feedback
RG escape controls phase transitions
Lucy Spardy
rhythm with/without feedback: what is the difference?
drive
drive
idea: drive strength affects timing of INF escape (end of stance), RGE, RGF escape but not timing of INE escape
OP : how does feedback shelter INE from drive?
Conclusions
• escape and release are different transition mechanisms that can yield similar rhythms in synaptically coupled networks
• in respiration, different mechanisms are predicted to be involved in different transitions
• transition mechanisms within one network may change with changes in state
• transition mechanisms determine responses to changes in drives to particular neurons – could be key for feedback control
THANK YOU!