Mesodiencephalic junction Gabaergic inputs are processed separately from motor cortical inputs in the basilar pons

The basilar pontine nuclei (bPN) receive inputs from the entire neocortex and constitute the main source of mossy fibers to the cerebellum. Despite their critical position in the cortico-cerebellar pathway, it remains unclear if and how the bPN process inputs. An important unresolved question is whether the bPN strictly receives excitatory inputs or also receives inhibitory inputs. In the present study, we identified the mesodiencephalic junction as a prominent source of GABAergic afferents to the bPN. We combined optogenetics and whole-cell patch clamp recordings and confirmed that the bPN indeed receives monosynaptic GABA inputs from this region. Furthermore, we found no evidence that these inhibitory inputs converge with motor cortex (M1) inputs at the single neuron level. We also found no evidence of any connectivity between bPN neurons, suggesting the absence of a local circuit. Finally, rabies tracings revealed that GABAergic MDJ neurons themselves receive prominent inputs from neocortical output neurons. Our data indicates that inhibition from the MDJ, and excitation from the neocortex remain separate streams of information through the bPN. It is therefore unlikely that inhibition in the bPN has a gating function, but rather shapes an appropriate output of the bPN during behavior.

Brain Processing of a Visual Self-Motion Study in Patients With Migraine: An fMRI Study

Objective:To investigate the behavioral and neuronal responses of patients with migraine to a visual stimulation of self-motion through a virtual roller coaster ride, in comparison to controls.Methods:Twenty consecutive migraine patients from a university-based hospital headache clinic and 20 controls were included. Participants underwent an experiment where a visually displayed self-motion paradigm was presented based on customized roller coaster videos during fMRI. Within each video, blocks of motion stimulation were interleaved with low speed upward motion in a random order. In the scanning intervals and after the experiment, participants rated their perceived level of vestibular symptoms and motion sickness during the videos. We hypothesized that migraine patients will perceive more motion sickness and that this correlates with a different central processing and brain responses.Results:Compared to controls, migraine patients reported more dizziness (65% versus 30% p= 0.03) and motion sickness [SSQ score 47.3 (95%CI 37.1, 57.5) versus 24.3 (95%CI 18.2, 30.4)] as well as longer symptom duration [01:19 min (95%CI 00:51, 01:48) versus 00:27 min (95%CI 00:03, 00:51)] and intensity [VAS 0-100, 22.0 (95%CI 14.8, 29.2) versus 9.9 (95%CI 4.9, 14.7)] during the virtual roller coaster ride. Neuronal activity in migraine patients were more pronounced in clusters within the superior [Contrast estimate 3.005 (90%CI 1.817, 4.194)] and inferior occipital gyrus [Contrast estimate 1.759 (90%CI 1.062, 2.456)], pontine nuclei [Contrast estimate 0.665 (90%CI 0.383, 0.946)] and within the cerebellar lobules V/VI [Contrast estimate 0.672 (90%CI 0.380, 0.964)], while decreased activity was seen in the cerebellar lobule VIIb [Contrast estimate 0.787 (90%CI 0.444, 1.130)] and in the middle frontal gyrus [Contrast estimate 0.962 (90%CI 0.557, 1.367)]. These activations correlated with migraine disability (r= -0.46, p= 0.04) and motion sickness scores (r= 0.32, p= 0.04). We further found enhanced connectivity between the pontine nuclei, cerebellar areas V/VI, interior and superior occipital gyrus with numerous cortical areas in migraine patients but not in controls.Conclusions:Migraine is related to abnormal modulation of visual motion stimuli within superior and inferior occipital gyrus, middle frontal gyrus, pontine nuclei, cerebellar lobules V, VI and VIIb. These abnormalities relate to migraine disability and motion sickness susceptibility.

Topography of corticopontine projections is controlled by postmitotic expression of the area-mapping gene Nr2f1

Axonal projections from layer V neurons of distinct neocortical areas are topographically organized into discrete clusters within the pontine nuclei during the establishment of voluntary movements. However, the molecular determinants controlling corticopontine connectivity are insufficiently understood. Here, we show that an intrinsic cortical genetic program driven by Nr2f1 graded expression in cortical progenitors and postmitotic neurons is directly implicated in the organization of corticopontine topographic mapping. Transgenic mice lacking cortical expression of Nr2f1 and exhibiting areal organization defects were used as model systems to investigate the arrangement of corticopontine projections. Combining three-dimensional digital brain atlas tools, Cre-dependent mouse lines, and axonal tracing, we show that Nr2f1 expression in postmitotic neurons spatially and temporally controls somatosensory topographic projections, whereas expression in progenitor cells influences the ratio between corticopontine and corticospinal fibers passing the pontine nuclei. We conclude that cortical gradients of area patterning genes are directly implicated in the establishment of a topographic somatotopic mapping from the cortex onto pontine nuclei.

Convergence of forepaw somatosensory and motor cortical projections in the striatum, claustrum, thalamus, and pontine nuclei of cats

The basal ganglia and pontocerebellar systems regulate somesthetic-guided motor behaviors, and receive prominent inputs from sensorimotor cortex. Additionally, the claustrum and thalamus are forebrain subcortical structures that have connections with somatosensory and motor cortices. Our previous studies in rats have shown that primary and secondary somatosensory cortex (S1 and S2) send overlapping projections to the neostriatum and pontine nuclei, whereas overlap of primary motor cortex (M1) and S1 was much weaker. Additionally, we have shown that M1, but not S1, projects to the claustrum in rats. The goal of the current study was to compare these rodent projection patterns with connections in cats, a mammalian species that evolved in a separate phylogenetic superorder. Three different anterograde tracers were injected into the physiologically identified forepaw representations of M1, S1, and S2 in cats. Labeled fibers terminated throughout the ipsilateral striatum (caudate and putamen), claustrum, thalamus, and pontine nuclei. Digital reconstructions of tracer labeling allowed us to quantify both the normalized distribution of labeling in each subcortical area from each tracer injection, as well as the amount of tracer overlap. Surprisingly, in contrast to our previous findings in rodents, we observed M1 and S1 projections converging prominently in striatum and pons, whereas S1 and S2 overlap was much weaker. Furthermore, whereas rat S1 does not project to claustrum, we confirmed dense claustral inputs from S1 in cats. These findings suggest that the basal ganglia, claustrum, and pontocerebellar systems in rat and cat have evolved distinct patterns of sensorimotor cortical convergence.