Independent Two-Colour Control of Neuronal Activity
Optogenetic Technologies and Applications
2019
2019 Optogenetic Technologies and Applications Conference
General Submissions
Optogenetics in Biomedicine - Neurobiology
Synaptic plasticity, the activity-dependent strengthening or weakening of the connections (synapses) between coincidently active neurons in the brain, underlies learning and memory. Repetitive pairing of activity (spiking) leads to synaptic potentiation when the presynaptic input is causal (i.e. precedes spiking of the postsynaptic neuron) or to depression when the presynaptic input follows spiking of the postsynaptic neuron (anti-causal). However, it has not been possible to study the long-term consequences of such sequences of activity due to the invasive nature of the intracellular recordings that are needed to assess synaptic strength and control spiking of the postsynaptic neurons. We have developed an optogenetic method for studying spike-timing-dependent plasticity (oSTDP), thereby greatly extending the observation window from approximately 30 minutes to three days in brain (hippocampal) slice cultures. We use CheRiff and ChrimsonR to independently control pre- and postsynaptic spiking and observe changes in synaptic strength consistent with the classical spike-timing-dependent plasticity rules described above, during whole-cell patch-clamp recordings. Surprisingly, when the neurons are left untouched during oSTDP induction and relative synaptic strength is assessed 3 days later, only potentiation is observed regardless of the pre-post timing sequence. We have also developed an extremely violet/blue light sensitive potassium channel that can be combined with a Chrimson variant to switch neurons on or off with yellow/red or violet light, respectively. Using these tools we are exploring further the rules that set synaptic strength and that determine the pattern of connections in the hippocampal circuit.