Abstract
Dendritic coincidence detection is fundamental to neuronal processing yet remains largely unexplored in awake animals. Specifically, the underlying dendritic voltage-calcium relationship has not been directly addressed. Here, using simultaneous voltage and calcium two-photon imaging of Purkinje neuron spiny dendrites, we show how coincident synaptic inputs and resulting dendritic spikes modulate dendritic calcium signaling during sensory stimulation in awake mice. Sensory stimulation increased the rate of postsynaptic potentials and dendritic calcium spikes evoked by climbing fiber and parallel fiber synaptic input. These inputs are integrated in a time-dependent and nonlinear fashion to enhance the sensory-evoked dendritic calcium signal. Intrinsic supralinear dendritic mechanisms, including voltage-gated calcium channels and metabotropic glutamate receptors, are recruited cooperatively to expand the dynamic range of sensory-evoked dendritic calcium signals. This establishes how dendrites can use multiple interplaying mechanisms to perform coincidence detection, as a fundamental and ongoing feature of dendritic integration in behaving animals.
Highlights
Dendritic integration is fundamental to signal processing in the brain
To study dendritic integration in vivo, we recently developed a fast (2 kHz) two-photon imaging technique to simultaneously record dendritic voltage and calcium signals from Purkinje neuron (PN) spiny dendrites in awake mice
Single PNs in lobule V of the cerebellar vermis were double labeled with voltage sensitive dye ANNINE-6plus and genetically encoded calcium indicator GCaMP6f, as described previously (Roome and Kuhn, 2018)
Summary
Dendritic integration is fundamental to signal processing in the brain. So far, most studies on dendritic integration have been performed in vitro, in the absence of physiological inputs (Larkum et al, 2009; Markram et al, 1997; Stuart and Hausser, 2001; Wang et al, 2000). In vivo calcium imaging from spiny dendrites can partially circumvent this issue (Chen et al, 2012). This approach measures dendritic calcium events only and omits the depolarizing and hyperpolarizing voltage signals evoked by synaptic input that do not trigger postsynaptic calcium signals. These synaptic potentials are expected to generate continuous but highly inhomogeneous spatiotemporal dendritic activity in awake animals. Our understanding of the basic components of dendritic integration, the frequency, amplitude, and spatiotemporal distribution of synaptic inputs under physiological conditions, and how these inputs are integrated by dendrites in awake behaving animals, remains incomplete
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