Basal Ganglia

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Basal Ganglia
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BASAL GANGLIA

• Involved in the control of movement
• Dysfunction associated with Parkinsons and
  Huntingtons disease
• Site of surgical procedures
• -- Deep Brain Stimulation (DBS)

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STN
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Deep Brain Stimulation (DBS)
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Parkinsons disease associated with
Loss of dopamine
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Parkinsons disease associated with
changes in firing patterns.

• Some neurons within basal ganglia exhibit
• Increased synchronization
• Increased bursting activity

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Why should these changes in firing patterns lead
to the motor symptoms seen in PD?
cortex
basal ganglia
thalamus
Inhibitory synapses
Strong pathological output patterns of BG inhibit
motor activity.
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MODELING STUDY

• Construct model GPe/STN network.

• Plenz Kitai showed that a GPe/STN network
  can display synchronous activity.

• Can the network generate both synchronous,
  tremor-like rhythms and irregular, uncorrelated
  activity?

• Mechanism underlying DBS?

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MODEL STN NEURON
Based on Experiments (Bevan and Wilson)
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Firing Properties of STN Cells
Experiment
Model
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Firing Properties of STN/GPE Neurons
STN
GPE
Post Inhibitory Rebound
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STN / GPe NETWORK
STRIATUM
Can this network exhibit both irregular and
correlated activity (same architecture,
different parameters) ?
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Irregular firing
Clustering
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When does the network exhibit irregular or
correlated activity?

• 10 STN GPe cells
• Sparse, structured
• coupling

PCA
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Analysis of Irregular Firing
Consider a Periodically Forced GPe Cell
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MODEL GPe NEURON
We consider Ca as a slow variable.
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GPe bifurcation diagram
stable periodic orbits
Saddle-node of limit cycles
Hopf bifurcation
Stable fixed pts
unstable fixed pts
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Dynamics Reduce to a Single Equation for the Slow
Variable
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A one-dimensional map
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Linear Approximation of Map
p(t)
TGPe gt TSTN
TGPe period of an isolated, bursting, GPe
cell. TSTN interval between STN spikes TS
GPe silent phase TA GPe active phase
TA
TGPe - TSTN
TSTN
TSTN-TS
t TGPe - TSTN TSTN - TGPe lt t
TSTN -TS (?s/?A)(TSTN - t) TSTN
- TS lt t TSTN
p(t)
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Tent map predicts

• ?S lt ?A number of spikes per burst is nearly
  constant
• ?S gt ?A number of spikes per burst may vary
  chaotically

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Numerically Computed Map
TGPe lt TSTN
TGPe gt TSTN
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Poincare Section
Remark This analysis does a very good job in
predicting when irregular
activity arises in larger networks.
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STN
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Mechanisms Underlying DBS Mysterious
Poorly understood

• Which neurons DBS acts on.
• How DBS effects different parts of neurons.
• How DBS depends on geometry of neurons.
• Whether DBS is excitatory or inhibitory.
• That is, does DBS increase or decrease
  output from stimulated structure?

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Evidence That DBS is Inhibitory

• Clinical effects similar to ablative surgery
• There is increased BG activity during PD

Evidence That DBS is Excitatory

• Recent experimental data (Vitek et al.)

Question How can one explain improvement of PD
symptoms if DBS increases GPi output activity?
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How Does Input From BG Effect Thalamic Ability
to Relay Excitatory Input?
???
Normal
Thalamus
Parkinson
DBS
Basal Ganglia
ExcitatoryInput
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Irregular (Normal) Activity
Basal ganglia
Thalamus
STN
GPi
TC
exc. input
DBS
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PD DBS off
DBS off
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PD DBS on
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PD DBS on ?off
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Data-driven computational study

• We now consider signal obtained from single-unit
• GPi recordings from
• control (normal) monkeys
• parkinsonian (MPTP) monkeys without DBS
• parkinsonian monkeys under sub-therapeutic
  STN-DBS
• parkinsonian monkeys under therapeutic STN-DBS

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(No Transcript)
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Normal PD w/o DBS sub-DBS therapeutic DBS
EST elevated spiking time of GPi
signal
small low firing rate medium bursting large
high tonic firing
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Collaborators
Charles Wilson Jonathan Rubin Yixin Guo Cameron
McIntyre Jerold Vitek Janet Best Choongseok Park