Presynaptic plasticity: targeted control of inhibitory networks

GABAergic inhibitory interneurons are embedded in almost all central neuronal networks, where they act to influence cell excitability, spike timing, synchrony, and oscillatory activity, that is, almost every physiologically relevant process in the mammalian central nervous system. Consequently, presynaptic plasticity of the synaptic input onto, or the outputs from, a single inhibitory interneuron can have major ramifications for the activity of the often thousands of downstream target neurons. Here we discuss several recently described forms of presynaptic long-term potentiation (LTP) and long-term depression (LTD) occurring at synapses either made onto inhibitory interneurons, or at inhibitory synapses onto downstream targets in a number of central structures. As we will illustrate, the induction mechanisms underlying these disparate examples of presynaptic plasticity share few common features, however, their expression mechanisms converge on the presynaptic release machinery. We hypothesize that these varied forms of presynaptic plasticity can operate in a manner fundamentally distinct from most postsynaptic ‘point to point’ forms of plasticity, to achieve powerful modification of the integration and output of large-scale networks.