[PhD Thesis Presentation_Zoom] ‐ Ms. Sakurako Watanabe - "Interaction of multiple inputs in plasticity of the corticostriatal synapses"

Presenter: Ms. Sakurako Watanabe

Supervisor: Prof. Jeffery Wickens

Unit: Neurobiology Research Unit

Zoom URL: no more available

Title: Interaction of multiple inputs in plasticity of the corticostriatal synapses

Abstract:

Spike timing-dependent plasticity (STDP) is a form of synaptic plasticity and physiologically relevant model of Hebbian learning. STDP depends on the relative timing of pre- and postsynaptic action potentials. In the brain, synaptic plasticity occurs in the context of concurrently occurring multiple inputs into the same neuron. Current theoretical and computational models assume that each presynaptic conditioning signal is independently processed in the neuron. However, in experimental STDP studies, different time points are measured in different cells rather than in the same cell. In the striatum, in particular spiny projection neurons (SPNs) receive many inputs including cortical and dopaminergic inputs during learning. Here, we investigated the plasticity of contiguous inputs from the cortex depending on their relative timing to firing in the SPN and tested whether dopamine could differentially modulate plasticity from those inputs. We performed whole-cell electrophysiological recordings in the SPNs of the dorsal medial striatum (DMS) of the acute brain slices of mice that express Drd1a/Drd2-eGFP or Drd1a-tdTomato to dentify SPN cell type (D1 or D2). We also used Ai32 (RCL-ChR2(H134R)/EYFP) / DAT-Cre / Drd1a-tdTomato triple transgenic mice to enable temporally controlled release of dopamine with optogenetics. In order to test this selection ability, we stimulated cortical afferents from two independent sets of bipolar electrodes, each stimulating at different times in relation to SPN firing. We found that two presynaptic inputs interact with each other and show sublinear, linear or superlinear summation when stimulated simultaneously. In our STDP protocol, two near-simultaneous inputs were applied to a single dSPN; one input (S1) at positive timing and the other (S2) at negative timing in relation to postsynaptic firing. Surprisingly, both pre-post and post-pre pairing resulted in a decrease in normalized EPSPs, indicating long-term depression (LTD). This contrasts with the results of standard STDP protocols with single inputs, which show different direction of plasticity depending on the relative timing to firing. In addition, we tested whether these inputs were sufficient to induce plasticity in the absence of postsynaptic firing. When only S1 and S2 inputs were recorded without postsynaptic firing, LTD was observed. This suggests that EPSPs in close temporal proximity could initiate plasticity. We then applied dopamine two seconds after each pairing, which is known to induce LTP when tested with one presynaptic input. We found that interaction of multiple cortical inputs changes the outcome of corticostriatal STDP. In summary, the results suggest that multiple contiguous presynaptic inputs to the same neuron can induce plasticity independently, but they can also interact with each other and affect plasticity outcome. This is the first study demonstrating the ability of SPNs to differentiate multiple plasticity-inducing inputs from the cortex. The results with dopamine stimulation suggest that certain interaction of multiple cortical inputs favours LTP to occur with the right timing of rewarding dopamine application. This highlights the importance of a transient eligibility trace in the synapse to enable LTP and subsequent learning to occur.