Modelling Bursting Pacemaker Neural Network
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Rahul BatraModelling Bursting Pacemaker Neural Network
Uploaded by
Rahul BatraModelling Bursting
Pacemaker Neuronal
Network
Based on: Models of Respiratory Rhythm Generation in the
Pre-Botzinger Complex. III. Experimental Tests of Model Predictions
Christopher A. Del Negro, Sheree M. Johnson, Robert J. Butera, Jeffery
C. Smith
BY-
RAHUL BATRA
MT13049
Introduction
Pre-Bötzinger Complex(Pre-BotC)-
A cluster of interneurons in ventrolateral medulla
Hypothesized site for respiratory rhythm generation in
mammals
Pacemaker Neurons-
Pre-BotC houses a heterogeneous population of bursting
pacemaker neurons
Respiratory rhythm generation mechanism incorporates an
excitatory network of synaptically coupled pacemaker
neurons
Background of Research Paper
In the first two paper of this series , Butera et al. created
mathematical models of inspiratory pacemaker neurons,
which were assembled to form a network model of rhythm
generating kernel
In this paper we evaluate basis for the models and the
predictions that emerged from modelling studies at cellular
and network levels
The objective of this paper is to show that pacemaker
neuron and network models successfully predicted features
of inspiratory rhythm generation in vitro in the Pre-BotC
Experimental Method
Thin slices were cut from the medulla of neonatal rats in
ACSF that captured the Pre-BotC and XIIn rootlets
Rhythmic respiratory activity was maintained by raising the
ACSF K+ concentration ([K+]o )
Inspiratory related motor discharge was recorded from the
XIIn rootlets and inspiratory neuron population was
simultaneously recorded from the Pre-BotC using macro
patch suction electrodes
Measurement of cellular and network activity such as
inspiratory burst period, frequency, and burst duration were
determined
To identify pacemaker neurons CNQX and low Ca2+
solution was used
A schematic showing the 350-μm-thick neonatal rat medullary
slice preparation and typical recording configuration
Pre-BotC activity preceded XIIn activity by 100-400 ms, which proves that
rhythm generation originates in the Pre-BotC
Mathematical Model
Pacemaker Neuron Model
It is composed of five ionic currents across the plasma membrane:
a fast sodium current, INa
a delayed rectifier potassium current, IK
a fast activating slowly inactivating persistent sodium current, INaP
a passive leakage current, IL
a tonic current, Itonic_e ( Itonic_e is considered to be inactive in single cell
simulations)
Model Formulation
Simulations
Simulations
At the highest Ek = -72 mV neuron exhibits tonic spiking
At hyperpolarized Vm , Ek = -80 mV model is quiescent
Ek is used to depolarize Vm , resulting in bursting oscillations
Results
A monotonic increase in burst frequency and decrease in
burst duration with increasing [K+]o concentration reflecting
the inactivation kinetics of INaP
Multistate behaviour with transitions from quiescence to
bursting and tonic spiking states as cells depolarizes i.e.
cellular excitability was increased via extracellular [K+]o
concentration
This model incorporates the minimum set of conductances
to generate bursting similar to pacemaker cells in the Pre-
BotC
Effect of Ca2+ current
Results
Intrinsic bursting behaviour did not depend on Ca2+ currents
and persisted after blocking synaptic transmission
Switching to low Ca2+ + CNQX solution did not
significantly affect burst duration nor the spike frequency –
time relationship
INaP dominates the burst generating mechanism of
pacemaker neuron model
Burst generation mechanism in inspiratory pacemaker
neurons is a Ca2+ independent persistent Na+ current
Conclusion
Pacemaker neuron model explains the features of
respiratory rhythm generation in Pre-BotC
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? Questions ?
