1. Introduction to the mathematical modeling of neuronal networks Amitabha Bose Jawaharlal Nehru University & New Jersey Institute of Technology IISER, Pune February 2010 bose.jnu@gmail.com

2. Typical Neuron Applied Mathematician’s Neuron Mathematician’s Neuron

3. Why are action potentials important? Action potentials are measurable events The timings or firing rate of action potentials can encode information - place cells in hippocampus - coincidence detection for sound localization - orientation selectivity in visual cortex Neurons can communicate with one another using action potentials

4. Synaptic Communication An action potential in the pre-synaptic neuron provides a current to the post-synaptic cell. The effect may be either excitatory (naively thought to promote firing of post-synaptic neuron) or inhibitory (naively having the opposite effect). Synapses have their own time scales for rise and decay. Synaptic delays may be involved. Synapses can change strength as a function of usage; this is called synaptic plasticity. Pre-synaptic neuron Post-synaptic neuron

5. Crustacean Pyloric Rhythm (CPG) PD LP PY Hooper 94, 95 Bean, Nature Rev. Neuro. 2007

6. Modeling a neuron as an RC circuit Membrane separates charge Ions flow through channels causing voltage changes

7. Hodgkin-Huxley type equations

8. Outline Examples of neuronal computation Complications for modeling Understanding the Hodgkin-Huxley equations Simple models to analyze synchronous and anti-phase oscillations

9. Place cells Pyramidal cells in hippocampus fire only when animal is in a specific, known location (transient & stable) Uses visual cues to trigger memory recall O’Keefe (1971)

10. Model for place cell firing (Bose, Booth,Recce 2000) TP I1I1 I2I2 Inhibition Excitation PLACE FIELD P = synchronous group of place cells

11. Place cells Place cells also code for location in 2-dimensional environment. They interact with head direction cells.

12. Auditory Cortex Coincidence detection Neurons have higher firing rate when they get coincidental input from left and right ears Owls use this to locate prey and prey to locate owls Jeffress delay line model for barn owls (1948)

13. Model for coincidence detection (Cook et al, 2003, Grande & Spain 2004) O1O2 NL P O1 O2 Calculate NL firing rate as a function of phase independent of frequency of O 1 and O 2

14. Visual Cortex Neurons fire at preferential orientations

15. Visual Cortex Very well suited to detecting orientations, contrasts, directions of movement, yet cannot resolve certain visual scenes. Necker Cube

16. Basal Ganglia - Parkinsonian Tremor Normal state: Irregular, no correlations in STN cells Parkinsonian state: Rhythmic, STN cells cluster Rubin & Terman, 2004

17. Central Pattern Generator Important for coordinated movement of muscle groups. Rhythmic and very stable behavior Crustacean Pyloric Rhythm (CPG) PD LP PY Nadim et al, 2000’s

18. Lung Episode Buccal Episode Overlaid traces show that the lung bursts begin at same point in buccal cycle as in PIR. Overlaid traces show that the buccal cycles continue predictably from last lung burst. Ventilatory Rhythms Wilson et al 2002 Lung Area Buccal Area

19. Different types of bursting neurons (students - ask Pranay about this!)

20. Modelers Goldmine or Minefield? ( title borrowed from K.B. Sinha ) Many complications: high dimensionality, multiple time scales, stochasticity, noise, large networks, unknown architecture… Many advantages: “young field”, no canonical equations thus much freedom, growing number of interactions with experimentalists Q. What is the appropriate level of detail for modeling? Q. Is there any fun mathematics to be done?

21. General Biological Questions What accounts for the rhythmic activity? Under what circumstances do synaptic and intrinsic properties of neurons cooperate or compete? What effect do multiple time scales have? What are the underlying neural mechanisms that govern behavior?

22. Translation to mathematics What accounts for the rhythmic activity? Periodic solutions in phase space Under what circumstances do synaptic and intrinsic properties of neurons cooperate or compete? Effect of parameters on solutions What effect do multiple time scales have? Singular perturbation theory What are the underlying neural mechanisms that govern behavior? Deriving mathematically minimal models that reveal necessary and sufficient conditions

23. To the blackboard!