Testing Models of Synaptic Plasticity in Neural Networks

Testing Models of Synaptic Plasticity in Neural Networks of Defined Connectivity James Fodor, November 2019 Scientifica. “Optogenetics: Shedding light on the brain's secrets. ”; Hewitt. “The first real-time, non-invasive imaging of neurons forming a neural network. ”; Ming-Gang et al. "Use of multi-electrode array recordings in studies of network synaptic plasticity in both time and space. ” (2012).

Hebbian plasticity • ‘Cells that fire together, wire together’ • Local learning rule Mc. Auliffe, Conor. “Synaptic Plasticity (Long Term Potentiation and Depression). ”

Hebbian plasticity in experiments • Based on EPSPs or EPSCs Yu-feng et al. , "Optogenetics and synaptic plasticity. " (2013).

Hebbian plasticity in theory

Hebbian plasticity in theory • Rate-based models • Definition of synaptic weight • Basic Hebbian plasticity rule

Hebbian plasticity in theory • Many rate-based Hebbian learning models. . .

Testing theory Requirements: 1. Precise control of neural connectivity 2. Ability to record pre- and post-synaptic activity 3. Ability to stimulate precise neural ensembles

Testing theory Grow in vitro network of hippocampal neurons from a rat Renault et al. "Combining microfluidics, optogenetics and calcium imaging to study neuronal communication in vitro. ” (2015). Forró et al. "Modular microstructure design to build neuronal networks of defined functional connectivity. ” (2018).

1. Control of connectivity • Use polydimethylsiloxane (PDMS) microstructures • Wells are sites for neuron soma • Channels allow growth of axons Forró et al. (2018).

2. Recording of neural activity • Use multielectrode array • 60 MEA 500/30 i. R-Ti for large distance between electrodes Forró et al. (2018).

3. Precise stimulation • Use channelrhodopsin (Ch. R 2) • Fibre-connected LEDs (470 nm) Renault et al. (2015); Silicon Lightwave Technology, Inc. “Single/Multi-Wavelengths Very High Power Turn-Key LED Sources. ”

Experimental setup

Experimental setup

Experimental setup

Experimental setup

Experimental setup LED LED

Experimental setup LED LED

Experimental setup Measure: LED LED

Stimulation protocol • Increase stimulation frequency in multiples of 2 (for ~1 s) • Various combinations of presynaptic neurons Welkenhuysen, Marleen, et al. "An integrated multi-electrode-optrode array for in vitro optogenetics. ” (2016).

Stimulation protocol 50. 0 45. 0 Postsynaptic firing rate Stimulus Frequency (Hz) Presynaptic 1 Presynaptic 2 1 0 2 0 4 0 8 0 16 0 32 0 64 0 128 0 256 0 512 0 1024 0 0 1 0 2 0 4 0 8 0 16 0 32 0 64 0 128 0 256 0 512 0 1024 1 1 2 2 4 4 8 8 16 16 32 32 64 64 128 256 512 1024 R 2 = 0. 8372 40. 0 35. 0 30. 0 25. 0 20. 0 15. 0 10. 0 5. 0 0 20 40 60 Presynaptic firing rate 80 100

Test theories • Test models for statistical significance on collected data

Potential limitations • No glial cells • Assembly of around 20 neurons • Highly artificial setup • Not clear if noise will be too great to detect signal

References 1. Dayan, Peter, and Laurence F. Abbott. Theoretical neuroscience: computational and mathematical modeling of neural systems. The MIT Press, 2001. 2. Forró, Csaba, et al. "Modular microstructure design to build neuronal networks of defined functional connectivity. " Biosensors and Bioelectronics 122 (2018): 75 -87. 3. Gerstner W, Kistler WM. “Mathematical formulations of Hebbian learning”. Biological cybernetics 87 (2016): 404 -415. 4. Hewitt, John. “The first real-time, non-invasive imaging of neurons forming a neural network. ”, https: //www. extremetech. com/extreme/179223 -the-first-real-time-non-invasive-imaging-of-neurons-forming-a-neuralnetwork. 5. Liu, Ming-Gang, et al. "Use of multi-electrode array recordings in studies of network synaptic plasticity in both time and space. " Neuroscience bulletin 28, no. 4 (2012): 409 -422. 6. Mc. Auliffe, Conor. “Synaptic Plasticity (Long Term Potentiation and Depression). ”, https: //sites. google. com/site/mcauliffeneur 493/home/synaptic-plasticity. 7. Renault, Renaud, et al. "Combining microfluidics, optogenetics and calcium imaging to study neuronal communication in vitro. " Plo. S one 10, no. 4 (2015): e 0120680. 8. Rolls, Edmund T. Memory, attention, and decision-making. OUP Oxford, 2008. 9. Scientifica, “Optogenetics: Shedding light on the brain's secrets. ”, https: //www. scientifica. uk. com/learningzone/optogenetics-shedding-light-on-the-brains-secrets. 10. Silicon Lightwave Technology, Inc. “Single/Multi-Wavelengths Very High Power Turn-Key LED Sources. ”, http: //slwti. com/LEDSources. aspx. 11. Trappenberg, Thomas. Fundamentals of computational neuroscience. OUP Oxford, 2009. 12. Welkenhuysen, Marleen, et al. "An integrated multi-electrode-optrode array for in vitro optogenetics. " Scientific reports 6 (2016): 20353.