Dynamic homeostatic plasticity within cerebellar circuitry

Abstract

The cerebellum has proved useful as a model system due to its uniform modular organization and explicit physiological significance of input and output signals. The cerebellum of the mormyrid fish provides a special opportunity to directly determine how single PCs affect their target cells. Such an approach is nearly impossible in mammals.In this study of the mormyrid cerebellum, a Purkinje cell and its target cell were simultaneously patch-recorded in a slice preparation, as focal stimuli were used to activate the PC's parallel fibers (PFs) or single climbing fiber (CF). Upon establishment of synaptic connection between two PCs or a PC-DCN cell pair, three signals – PF responses in both cells and the synaptic inhibition from the pre- to the post-synaptic cell – were recorded as controls, followed by the conventional manipulations of pairing PF and CF inputs to induce long-term potentiation (LTP) or depression (LTD) at parallel fiber synapses onto the presynaptic cell. Then, the three signals are recorded again and contrasted with the controls.Surprisingly, we found that after PF-LTP was induced in the presynaptic cell, the synaptic inhibition from the same cell to the postsynaptic cell was significantly attenuated; conversely, after PF-LTD was induced in the presynaptic cell, the synaptic inhibition from same cell to postsynaptic cell was significantly enhanced. These results indicate that synaptic plasticity at input synapses of the mormyrid Purkinje cell are not simply conveyed to the same cell’s output synapses, as assumed in conventional theories of motor learning, but rather that the strength of a PC’s output synapses onto its target cells is up- and downregulated following LTD and LTP, respectively, at the same cell’s input synapses. We hypothesize that the runaway nature of Hebbian plasticity in a central neural network is buffered in an online fashion by changes generated by negative feedback at the same neuron’s output synapse, a phenomenon which we have termed dynamic homeostatic plasticity. National Science Foundation, Grant/Award Number: 1929489 to VZH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.