The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending inhibitory input to the floccular granule cell layer

Abstract

The basal interstitial nucleus (BIN) in the white matter of the vestibulocerebellum has been defined more than three decades ago, but has since been largely ignored. It is still unclear which neurotransmitters are being used by BIN neurons, how these neurons are connected to the rest of the brain and what their activity patterns look like. Here, we studied BIN neurons in a range of mammals, including macaque, human, rat, mouse, rabbit, and ferret, using tracing, immunohistological and electrophysiological approaches. We show that BIN neurons are GABAergic and glycinergic, that in primates they also express the marker for cholinergic neurons choline acetyl transferase (ChAT), that they project with beaded fibers to the glomeruli in the granular layer of the ipsilateral floccular complex, and that they are driven by excitation from the ipsilateral and contralateral medio-dorsal medullary gigantocellular reticular formation. Systematic analysis of codistribution of the inhibitory synapse marker VIAAT, BIN axons, and Golgi cell marker mGluR2 indicate that BIN axon terminals complement Golgi cell axon terminals in glomeruli, accounting for a considerable proportion ( > 20%) of the inhibitory terminals in the granule cell layer of the floccular complex. Together, these data show that BIN neurons represent a novel and relevant inhibitory input to the part of the vestibulocerebellum that controls compensatory and smooth pursuit eye movements.

Histochemical Characterization of the Vestibular Y-Group in Monkey

“…Our finding of few primarily small ChAT-positive neurons in the Yd is consistent with other reports [ 48 ]. These cholinergic neurons differ clearly in size and morphology from those in the adjacent BIN, which coexpress GABAergic markers and send projections to the flocculus [ 36 , 48 ].…”

“…Our finding of few primarily small ChAT-positive neurons in the Yd is consistent with other reports [ 48 ]. These cholinergic neurons differ clearly in size and morphology from those in the adjacent BIN, which coexpress GABAergic markers and send projections to the flocculus [ 36 , 48 ]. It is not clear, whether ChAT-positive neurons within the Yd represent local interneurons giving rise to the abundant network of ChAT-positive nerve fibres and varicosities found in the Yd neuropil (see Fig.…”

Re-evaluating Circuit Mechanisms Underlying Pattern Separation

“…While in general cerebellar granule cells only receive inhibition from Golgi cells-with the exception of recently discovered inhibitory feedback (Ankri et al, 2015;Guo et al, 2016) and external broad inhibition (Jaarsma et al, 2018) in specific regions-dentate granule cells are interconnected with multiple inhibitory interneuron subtypes, which are likely to be specialized for distinct functions (Halasy and Somogyi, 1993;Sik et al, 1997;Hosp et al, 2014;Savanthrapadian et al, 2014;Szabo et al, 2017). Of these, one of the most widely studied are basket cells, which receive synaptic input from granule cell axon collaterals and deliver feedback inhibition to the perisomatic regions of granule cells via their extensive axonal plexus (Ribak, 1992).…”

Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease

“…The basal interstitial nucleus is a group of neurons embedded in the white matter underlying the vestibulocerebellum, innervating the floccular cortex. In primates, some of these neurons may be cholinergic (Jaarsma et al, 2018).…”