title: Active integration of glutamatergic input to the inferior olive generates bidirectional postsynaptic potentials.
abstract: We establish experimental preparations for optogenetic investigation of glutamatergic input to the inferior olive. Neurones in the principal olivary nucleus receive monosynaptic extra-somatic glutamatergic input from the neocortex. Glutamatergic inputs to neurones in the inferior olive generate bidirectional postsynaptic potentials (PSPs), with a fast excitatory component followed by a slower inhibitory component. Small conductance calcium-activated potassium (SK) channels are required for the slow inhibitory component of glutamatergic PSPs and oppose temporal summation of inputs at intervals ≤ 20 ms. Active integration of synaptic input within the inferior olive may play a central role in control of olivo-cerebellar climbing fibre signals.
  
  
  
  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 AMPA (GluA) receptors, are GABAAindependent, 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.
authors: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK.
authors: Derek L F
authors: DL
authors: Garden
authors: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK.
authors: Arianna
authors: A
authors: Rinaldi
authors: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK.
authors: Matthew F
authors: 0000-0003-1062-6501
authors: MF
authors: Nolan
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009847:Olivary Nucleus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D055366:Synaptic Potentials
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D018698:Glutamic Acid; C064719:iberiotoxin
keywords: inferior olive; ion channel; synaptic integration