Active integration of glutamatergic input to the inferior olive generates bi-directional postsynaptic potentials

Derek Garden, Arianna Rinaldi, Matthew Nolan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex.
While it is well established that climbing fibre signals are important for motor
coordination, the mechanisms by which neurones in the inferior olive integrate
synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs. We demonstrate that optogenetically activated long-range synaptic inputs to the inferior olive, including projections from the motor cortex, generate rapid excitatory potentials followed by slower inhibitory potentials. Synaptic projections from the motor cortex preferentially target the principal olivary nucleus. We show that inhibitory and excitatory components of the bidirectional synaptic potentials are dependent upon GluA receptors, are GABAA-independent, and originate from the same presynaptic axons. Consistent with models that predict active integration of synaptic inputs by inferior olive neurones, we find that the inhibitory component is reduced by blocking large conductance calcium-activated potassium channels with
iberiotoxin, and is abolished by blocking small conductance calcium-activated
potassium channels with apamin. Summation of excitatory components of synaptic responses to inputs at intervals ≤ 20 ms is increased by apamin, suggesting a role for the inhibitory component of glutamatergic responses in temporal integration. Our results indicate that neurones in the inferior olive implement novel rules for synaptic integration and suggest new principles for the contribution of inferior olive neurones to coordinated motor behaviours.
Original languageEnglish
JournalThe Journal of Physiology
Early online date29 Nov 2016
DOIs
Publication statusE-pub ahead of print - 29 Nov 2016

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