Electrical coupling regulated by GABAergic nucleo-olivary afferent fibres facilitates cerebellar sensory-motor adaptation (Q6077662)

The vestibulo-ocular-reflex (VOR) is a reflex of the eye movement that stabilises the images on the retina during head movements by producing contralateral eye movements that maintain the image in the centre of the visual field. During rotational VOR, the vestibular system senses head rotation signals that are later processed in the vestibular nuclei and cerebellum to stabilise the eyes. The cerebellum and the vestibular nuclei are reciprocally inter-connected. Introduced method's results suggest that a systematic GABAergic NO deactivation decreases the spatio-temporal complexity of the IO firing patterns thereby worsening the temporal resolution of the olivary system. Conversely, properly coded IO spatio-temporal firing patterns, thanks to NO modulation, finely shape the balance between long-term depression and potentiation, which optimises VOR adaptation. Significantly, the NO connectivity pattern constrained to the same micro-zone helps maintain the spatio-temporal complexity of the IO firing patterns through time. Moreover, the temporal alignment between the latencies found in the NO fibres and the sensory- motor pathway delay appears to be crucial for facilitating the VOR. The research work first characterised the EC within an olivary system in isolation and verified that specific activations of its GABAergic inputs (i.e., NO axons), reduced the coupling coefficient (CC) amongst IOs. This reduction varies with the coupling distance: linearly under negative injected currents and exponentially under positive injected currents to the central IO. After the EC characterisation, then introduced new olivary system within a cerebellar spiking network located at the core of a feed forward controller acting during hCVOR adaptation. Determined that the exponential CC reduction via the NO pathway facilitated desynchronising the CF spike generation during cerebellar learning, as otherwise the accuracy and learning consolidation during h-VOR would be compromised. Introduced results also suggest that not only the GABAergic NO action, but also the NO pathway topology in closing the olivo-cortico-nucleo-olivary (OCNO) loop, are key in desynchronising the CF spike generation within the same micro-complex during h-VOR adaptation. The NO pathway topology was also found to be relevant in allowing single neuron olivary dynamics under GABAergic NO activations at initial adaptation stages Interestingly, we found a beneficial timing correspondence between the long latency of the NO pathway and the sensory-motor pathway delay \((\sim\) 100\,ms). The temporal alignment of the teaching signal with its neural consequences enhanced h-VOR performance. Concurrently, we verified a two-fold role of the complementary olivary-nuclei path \((IO-MVN)\) during h-VOR adaptation; (i) providing a coarse but prompt MVN synaptic response to the signalled error, (ii) adjusting the MVN temporal activation better to finely shape the subsequent neural drive motor commands.