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Optimality, robustness, and dynamics of decision making under norepinephrine modulation: A spiking neuronal network model. Joint work with Philip Eckhoff and Phil Holmes. Sloan-Swartz Meeting 2008. Experimental results: Cellular level.

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slide1

Optimality, robustness, and dynamics of decision making under norepinephrine modulation:A spiking neuronal network model

Joint work with Philip Eckhoff and Phil Holmes

Sloan-Swartz Meeting 2008

experimental results cellular level
Experimental results: Cellular level
  • Norepinephrine (NE) modulates EPSP, IPSP, cellular excitability
  • Locus coeruleus (LC) supplies NE throughout the brain
  • LC neurons exhibit tonic or phasic firing rate mode
  • [NE] release approx linear to tonic firing rate of LC

| | | || | | | | || | | | || |

Tonic mode

| | || ||||||| | | | | |

Phasic mode

Berridge and Abercrombie (1999)

experimental results behavioral level

Aston-Jones et. al (1999)

Aston-Jones and Cohen (2005)

Experimental results: Behavioral level

Inverted-U shape performance in behavioral tasks

past modeling work
Past modeling work

(i) Connectionist modeling e.g. Usher et al (1999); Brown et al (2004); Brown et al (2005)

(ii) Normative (Bayesian) approach e.g. Yu and Dayan (2005); Dayan and Yu (2006)

(iii) Biophysical modeling work are more concerned with signal-to-noise ratio, e.g. Hasselmo (1997); Moxon et al (2007).

slide5
Goal

To link cellular to behavioral level of LC-NE modulation, in the context of a decision-making reaction task task, and study the decision circuit’s performance (reward rate) using a spiking neuronal network model

a spiking neuronal network model for 2 alternative forced choice decision making tasks
A spiking neuronal network model for 2-alternative forced-choice decision-making tasks
  • Neuronal model: Leaky integrate-and fire
  • Recurrent excitatory synapses: AMPA, NMDA
  • Inhibition: GABAA
  • External inputs (background, stimulus): AMPA
  • Task difficulty depends on:

(I1 - I2) /(I1 + I2)

Decision time

Choice 1 made

I1

I2

X.-J. Wang (2002)

performance in a reaction time task rate of receiving reward
Performance in a reaction time task: Rate of receiving reward
  • Reward rate = (Total # of correct trials) / (Total time)
  • Total time = Sum of Reaction time + Response-to-stimulus interval
  • Reaction time = Decision time + non-decision latency

RT

RT

… …

… …

n trial

RSI

n+1 trial

Time

tonic lc ne modulation of both e and i cells provides robust decision performance
Tonic LC-NE modulation of both E and I cells provides robust decision performance

Assume linear LC [NE] gsyn

“1” denotes

standard set of parameters of Wang (2002)

Robust performance for modulation of NMDA or AMPA, as long as E and I cells are modulated together

neural dynamics under tonic modulation of e and i cells

Standard

Too high

Too low

Neural dynamics under tonic modulationof E and I cells

Unmotivated

Increasing

LC-NE

Standard/Optimal

Firing rate

Time

Impulsive

differential tonic modulation between e and i cells
Differential tonic modulation between E and I cells

There exists a maximum robustness when synapses of E cells are modulated about half that of I cells

single cell evoked response under tonic modulation
Single-cell evoked response under tonic modulation

Condition of maximum robustness also results in an inverted-U shape for single-cell evoked response. Since we used linear modulation, inverted-U shape is a pure network effect.

phasic lc ne modulation
Phasic LC-NE modulation

NE = 100 ms

Delay = 200 ms

[NE] = F(LC) for phasic?

dg / dt = G( [NE] ) ? Assume linear.

phasic modulation can provide further improvement in performance
Phasic modulation can provide further improvement in performance…

… provided glutamatergic modulation dominates over that of GABAergic synapses

conclusion
Conclusion
  • Inverted-U shape in decision performance
  • Tonic co-modulation of E and I cells provides robust performance (more expt on I cells needed to confirm)
  • Lesser affinity of E to I cells to tonic modulation results in: (i) maximum robust performance; (ii) inverted-U shape of single-cell evoked response (can be a pure network effect)
  • [NE] = F(LC) for phasic LC mode? If F is linear, our work shows that phasic modulation can further improve over tonic when modulation of glutamatergic synapses dominate over GABAergic.
acknowledgements
Acknowledgements
  • Barry Waterhouse, Drexel University College of Medicine
  • Jonathan Cohen, Princeton University
  • PHS grants MH58480 and MH62196
  • AFOSR grant FA9550-07-1-0537
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