Analyzing synaptic plasticity at the single cell level with STDP
Abstract Using patch clamp recordings in acutely isolated brain slices allows to investigate molecular processes that are involved in long-term potentiation (LTP) and long-term depression (LTD) at the level of a single postsynaptic neuron. Via the pipette solution in the recording pipette, it is possible to apply inhibitors of signaling cascades selectively into the postsynaptic neuron to unravel the molecular mechanisms of synaptic plasticity. In recent years, LTP research has been increasingly focused on induction protocols for LTP and LTD that rely on a minimal number of repeated synaptic stimulations at low frequency to induce synaptic plasticity. This is where spike timing-dependent plasticity (STDP) comes into play. STDP can be induced by repetitive pairings of action potential firing in presynaptic (first neuron) – and postsynaptic (second synaptically connected) neurons, that occurs with a delay of roughly 5–20 ms in forward or backward manner. While forward pairing with short positive time delays (“pre before post”) leads to LTP, backward pairing (“post before pre”) leads to LTD. In addition to the exact sequence and timing of pre- and postsynaptic spiking, the presence of neuromodulatory transmitters in the extracellular space (e. g., dopamine, acetylcholine, noradrenaline) and the synaptic release of intercellular mediators of synaptic plasticity (e. g., BDNF, endocannabinoids) critically regulate the outcome of STDP protocols. In this review we focus on the role of these mediators and modulators of synaptic plasticity in STDP.