Synaptic responses in the inferior olive to projections from the neocortex

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, C56

Oral Communications: Synaptic responses in the inferior olive to projections from the neocortex

D. L. Garden1, M. F. Nolan1

1. Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.

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The olivocerebellar circuit is involved in co-ordinating movements and in motor learning. Long-range inputs converge on a particular component of the circuit, the inferior olive (IO), which in turn projects via climbing fibres to Purkinje cells in the cerebellum. The output from inferior olive neurons is manifest as a complex spike, which is important for computations carried out by Purkinje cells. Inferior olive neurons receive inputs from the deep cerebellar nuclei and from the periphery via the spinal cord. Anatomical studies have suggested that neurons in the neocortex also project to the inferior olive, but their physiological role remains unclear. We virally transfected neurons of the neocortex with an adeno-associated virus expressing channelrhodopsin-2 (AAV-ChR2), with the aim of isolating neocortical inputs in to the inferior olive. Mice (5-6 weeks) were anesthetized with isoflurane (2%) while placed in a stereotaxic frame. Bilateral injections of AAV-ChR2-Venus (0.5 μl) were made in to the neocortex (AP: 1.1-1.6 mm, ML ±1.1-1.2 mm, DV -1.0 mm to bregma), and the animals allowed to recover for 3 weeks. After the recovery period, mice were anesthetized using the same procedure, their brains removed and 200 μm coronal IO sections were cut. Whole-cell recordings were then performed, and the responses of olivary neurons to optical stimulation of the transfected axons from neocortex measured. We find that light-evoked responses, specific to projections from the neocortex, can be reliably invoked in IO 3 weeks post-injection. Responses to neocortical input consist of a fast depolarizing component (peak 1.77 ± 0.09 mV n=6) followed by a large and relatively slow hyperpolarizing component (peak -2.54 ± 0.49 mV n=6). Minimal stimulation results in all-or-none responses (‘1V’ 2ms light pulse: slope 0.82 ± 0.26 mV/ms n=6) with a low probability of release (0.35 ± 0.09). These data provide evidence of functional connections between the neocortex and inferior olive. Understanding how these inputs affect neural computations in olivary neurons will contribute to understanding motor co-ordination.



Where applicable, experiments conform with Society ethical requirements.

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