scholarly journals Dendritic coincidence detection in Purkinje neurons of awake mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Christopher J Roome ◽  
Bernd Kuhn

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.

2020 ◽  
Author(s):  
Christopher J. Roome ◽  
Bernd Kuhn

SummaryDendritic coincidence detection is thought fundamental to neuronal processing, yet the underlying dendritic voltage-calcium relationship remains unexplored in awake animals. Here, using simultaneous voltage and calcium two-photon imaging of Purkinje neuron spiny dendrites, we show how coincident sub- and suprathreshold synaptic inputs modulate dendritic calcium signaling during sensory stimulation in awake mice. Sensory stimulation evokes subthreshold excitatory and inhibitory post-synaptic potentials, that coincide with suprathreshold dendritic spikes triggered by climbing fiber and parallel fiber synaptic input. Purkinje neuron dendrites integrate these inputs in a time-dependent and non-linear fashion to enhance the sensory evoked dendritic calcium signal. Intrinsic supra-linear 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 use multiple interplaying mechanisms to perform coincidence detection, as a fundamental and ongoing feature of dendritic integration during behavior.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chris H. Habrian ◽  
Joshua Levitz ◽  
Vojtech Vyklicky ◽  
Zhu Fu ◽  
Adam Hoagland ◽  
...  

AbstractMetabotropic glutamate receptors (mGluRs) are dimeric G-protein–coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity ~4000-fold lower than other mGluRs and a maximal activation of only ~10%, seemingly too low for activation at synapses. However, mGluR7 heterodimerizes, and we find it to associate with mGluR2 in the hippocampus. Strikingly, the mGluR2/7 heterodimer has high affinity and efficacy. mGluR2/7 shows cooperativity in which an unliganded subunit greatly enhances activation by agonist bound to its heteromeric partner, and a unique conformational pathway to activation, in which mGluR2/7 partially activates in the Apo state, even when its LBDs are held open by antagonist. High sensitivity and an unusually broad dynamic range should enable mGluR2/7 to respond to both glutamate transients from nearby release and spillover from distant synapses.


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