Abstract
The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.
Highlights
At most synapses, neurotransmitter release is rapid, highly synchronous and tightly associated with presynaptic firing (Borst and Sakmann, 1996; Katz and Miledi, 1965; Sabatini and Regehr, 1996)
Glycinergic boutons are present at modest levels in some regions of the rostral inferior olive (IO), and they are present at higher levels in the caudal IO and in the reticular formation (RF) surrounding the IO
We found that the two primary sources of inhibitory inputs to the IO are specialized to provide very different types of inhibition
Summary
Neurotransmitter release is rapid, highly synchronous and tightly associated with presynaptic firing (Borst and Sakmann, 1996; Katz and Miledi, 1965; Sabatini and Regehr, 1996). Within the IO, the properties of neurotransmitter release at inhibitory synapses are highly variable between different subnuclei (Best and Regehr, 2009; Turecek and Regehr, 2019). In some IO subnuclei, GABA release is exclusively asynchronous, for others release is exclusively synchronous, and for the rest release has both a synchronous and an asynchronous component. This influences the jitter, the rise time and the decay time of synaptic responses (Figure 1A, Turecek and Regehr, 2019). Release in the IO is synchronous if Syt1/2 are present, but asynchronous if they are absent (Turecek and Regehr, 2019), consistent with a role of Syt1/2 in release synchrony at other synapses (Bacaj et al, 2013; Chen et al, 2017; DiAntonio and Schwarz, 1994; Geppert et al, 1994; Kochubey and Schneggenburger, 2011; Xu et al, 2007)
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