The anatomical pathway from the mesodiencephalic junction to the inferior olive relays perioral sensory signals to the cerebellum in the mouse

Abstract

Key points Perioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell (PC) receives this signal as complex spikes (CSs) via a climbing fibre (CF) emerging from the inferior olive (IO).The anatomical pathway from trigeminal nuclei to the IO is not clearly identified.In the present study, we examined candidate anatomical pathways for perioral sensory signalling by analysing CSs recorded from PCs in male mice by single unit recording.CS generation by ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, which is referred to as the area parafascicularis prerubralis (PfPr). The number of CSs evoked by mechanical whisker stimulation was also decreased by contralateral PfPr inhibition.These results suggest the existence of a sensory signalling pathway to the IO via the PfPr in mice. AbstractPerioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell receives this signal as complex spikes (CSs) via a climbing fibre emerging from the inferior olive (IO). However, the anatomical pathway from the trigeminal nuclei to the IO is not clearly identified. In the present study, we recorded CSs from Purkinje cells in male mice by single unit recording, and examined the signal transduction pathway. CSs were evoked by electrical stimulation of the ipsilateral or contralateral ION with a latency of 20–70 ms. CS generation by ipsilateral ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, ranging from around the fasciculus retroflexus to the interstitial nucleus of Cajal, which is referred to as the area parafascicularis prerubralis (PfPr). CSs evoked by contralateral ION stimulation were also suppressed by muscimol injection into the PfPr, although the effective area was more restricted. Furthermore, CSs evoked by mechanical stimulation around the whisker region were suppressed by PfPr inhibition. We also found that the primary motor cortex plays a role to suppress this signalling pathway. These results indicate the existence of an anatomical pathway for conducting perioral sensory signals to the IO via the PfPr.

Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

“…Still, our present study is the first, to our knowledge, to directly demonstrate that S1 mediates sensory-evoked climbing fiber responses. In contrast to what we observed, a recent study by Kubo et al 62 reported that inhibition of the neocortex in mice did not inhibit CS. The reason for this discrepancy is unclear, but it may be that they explored only medial parts of the neocortex.…”

Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity

“…In line with the fact that PCs receive sensory whisker input not only directly from the brainstem but also indirectly from thalamo-cortical pathways (Figure 2F) (Kleinfeld et al, 1999; McElvain et al, 2018; Bosman et al, 2011; Brown and Raman, 2018; Kubo et al, 2018), the dynamics of their responses upon whisker stimulation are heterogeneous (Brown and Bower, 2001; Loewenstein et al, 2005; Bosman et al, 2010; Chu et al, 2011). To study the anatomical distribution of these responses within cerebellar lobules crus 1 and crus 2, we mapped the complex spike and simple spike firing of their PCs following ipsilateral whisker pad stimulation with air-puffs in awake mice.…”

Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis

“…PCs in the F1 rDLP module, located in medial parts of the simple lobule and Crus II, receive orofacial tactile signals ( Bower and Woolston, 1983 ), and fire action potentials time-locked to licking ( Welsh et al, 1995 ) and whisking ( Brown and Raman, 2018 ), as do the associated molecular layer interneurons ( Astorga et al, 2017 ). Inferior olive neurons in the F1 rDLP module (cMAO-c) respond to perioral stimuli driven by indirect trigeminal inputs from lateral superior colliculus ( Akaike, 1988 ) and the mesodiencephalic junction ( Kubo et al, 2018 ). These circuit connections make the F1 rDLP module well suited for contextual modulation of trigemino-motor reflexes and the adaptive coordination of multiple oromotor behaviors and breathing.…”