Experience-dependent plasticity in early stations of sensory processing in mature brains: effects of environmental enrichment on dendrite measures in trigeminal nuclei

Nervous systems respond with structural changes to environmental changes even in adulthood. In recent years, experience-dependent structural plasticity was shown not to be restricted to the cerebral cortex, as it also occurs at subcortical and even peripheral levels. We have previously shown that two populations of trigeminal nuclei neurons, trigeminothalamic barrelette neurons of the principal nucleus (Pr5), and intersubnuclear neurons in the caudal division of the spinal trigeminal nucleus (Sp5C) that project to Pr5 underwent morphometric and topological changes in their dendritic trees after a prolonged total or partial loss of afferent input from the vibrissae. Here we examined whether and what structural alterations could be elicited in the dendritic trees of the same cell populations in young adult rats after being exposed for 2 months to an enriched environment (EE), and how these changes evolved when animals were returned to standard housing for an additional 2 months. Neurons were retrogradely labeled with BDA delivered to, respectively, the ventral posteromedial thalamic nucleus or Pr5. Fully labeled cells were digitally reconstructed with Neurolucida and analyzed with NeuroExplorer. EE gave rise to increases in dendritic length, number of trees and branching nodes, spatial expansion of the trees, and dendritic spines, which were less pronounced in Sp5C than in Pr5 and differed between sides. In Pr5, these parameters returned, but only partially, to control values after EE withdrawal. These results underscore a ubiquity of experience-dependent changes that should not be overlooked when interpreting neuroplasticity and developing plasticity-based therapeutic strategies.

Brain-inspired spiking neural network controller for a neurorobotic whisker system

It is common for animals to use self-generated movements to actively sense the surrounding environment. For instance, rodents rhythmically move their whiskers to explore the space close to their body. The mouse whisker system has become a standard model to study active sensing and sensorimotor integration through feedback loops. In this work, we developed a bioinspired spiking neural network model of the sensorimotor peripheral whisker system, modelling trigeminal ganglion, trigeminal nuclei, facial nuclei, and central pattern generator neuronal populations. This network was embedded in a virtual mouse robot, exploiting the Neurorobotics Platform, a simulation platform offering a virtual environment to develop and test robots driven by brain-inspired controllers. Eventually, the peripheral whisker system was properly connected to an adaptive cerebellar network controller. The whole system was able to drive active whisking with learning capability, matching neural correlates of behaviour experimentally recorded in mice.

A vibrissa pathway that activates the limbic system

Vibrissa sensory inputs play a central role in driving rodent behavior. These inputs transit through the sensory trigeminal nuclei, which give rise to the ascending lemniscal and paralemniscal pathways. While lemniscal projections are somatotopically mapped from brain stem to cortex, those of the paralemniscal pathway are more widely distributed. Yet the extent and topography of paralemniscal projections are unknown, along with the potential role of these projections in controlling behavior. Here we used viral tracers to map paralemniscal projections. We find that this pathway broadcasts vibrissa-based sensory signals to brain stem regions that are involved in the regulation of autonomic functions and to forebrain regions that are involved in the expression of emotional reactions. We further provide evidence that GABAergic cells of the Kölliker-Fuse nucleus gate trigeminal sensory input in the paralemniscal pathway via a mechanism of presynaptic or extrasynaptic inhibition.

Experience-Dependent Plasticity in Early Stations of Sensory Processing in Mature Brains: Effects of Environmental Enrichment On Dendrite Measures in Trigeminal Nuclei

Nervous systems respond with structural changes to environmental changes even in adulthood. In recent years it has been shown that experience-dependent structural plasticity is not restricted to the cerebral cortex, but also occurs at subcortical and even peripheral levels. We have previously shown that two populations of trigeminal nuclei neurons, trigeminothalamic barrelette neurons of the principal nucleus (Pr5), and intersubnuclear neurons in the caudal division of the spinal trigeminal nucleus (Sp5C) that project to Pr5 underwent morphometric and topological changes in their dendritic trees after a prolonged total or partial loss of afferent input from the vibrissae. Here we examined whether and what structural alterations could be elicited in the dendritic trees of the same cell populations in young adult rats after being exposed for two months to an enriched environment (EE), and how these changes evolved when animals were returned to standard housing for an additional two months. Neurons were retrogradely labeled with dextran amine delivered to, respectively, the ventral posteromedial thalamic nucleus or Pr5. Fully labeled cells were digitally reconstructed with Neurolucida and analyzed with NeuroExplorer. EE gave rise to increases in dendritic length, number of trees and branching nodes, spatial expansion of the trees, and dendritic spines, which were less pronounced in Sp5C than in Pr5 and differed between sides. In Pr5 these parameters returned, but only partially, to control values after EE withdrawal. These results underscore a ubiquity of experience-dependent changes that should not be overlooked when interpreting neuroplasticity and developing plasticity-based therapeutic strategies.

Functional analysis of information rates conveyed by rat whisker-related trigeminal nuclei neurons

We studied two trigeminal nuclei containing the second neuron on the tactile pathway of whisker-related tactile information in rats. We found that the subnuclei, traditionally assumed to give rise to functional tactile channels, nevertheless transfer primary afferent information with quite similar properties in terms of integration time and kinematic profile. We discuss whether such commonality may be due the requirement to adapt to physical constraints of frictional whisker contact.

Vitamin C Acutely Affects Brain Perfusion and Mastication-Induced Perfusion Asymmetry in the Principal Trigeminal Nucleus

Prolonged mastication may induce an asymmetric modification of the local perfusion of the trigeminal principal nucleus. The aim of the present study was to evaluate the possible influence of vitamin C (vit. C) on such effect. Four groups of healthy volunteers underwent arterial spin labeling magnetic resonance imaging (ASL-MRI) to evaluate the local perfusion of the trigeminal nuclei after a vit. C-enriched lunch or a control lunch. Two ASL-MRI scans were acquired, respectively, before and after a 1 h-long masticating exercise or a 1 h long resting period. The results showed (i) an increased global perfusion of the brain in the vit. C-enriched lunch groups, (ii) an increased local perfusion of the right principal trigeminal nucleus (Vp) due to mastication, and (iii) a reduction of the rightward asymmetry of the Vp perfusion, due to mastication, after the vit C-enriched meal compared to the control meal. These results confirmed a long-lasting effect of prolonged mastication on Vp perfusion and also suggest a possible effect of vit. C on cerebral vascular tone regulation. Moreover, the data strongly draw attention on the side-to-side relation in Vp perfusion as a possible physiological parameter to be considered to understand the origin of pathological conditions like migraine.

Genetic Deletion of TrpV1 and TrpA1 Does Not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similar to wildtype (WT) mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford, Thompson, et al. 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in WT and TrpA1/V1 double-KO (TRPA1/V1Dbl−/−) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, and 30 mM citric acid, along with 100 µM SC45647 and H2O. Both WT and TRPA1/V1Dbl−/− show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36, respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid-avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Dbl−/− animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.

Spontaneous Axonal Dystrophy in the Brain and Spinal Cord in Naïve Beagle Dogs

Axonal dystrophy (AD) is a common age-related neurohistological finding in vertebrates that can be congenital or induced by xenobiotics, vitamin E deficiency, or trauma/compression. To understand the incidence and location of AD as a background finding in Beagle dogs used in routine toxicity studies, we examined central nervous system (CNS) and selected peripheral nervous system (PNS) tissues in twenty 18- to 24-month-old and ten 4- to 5-year-old control males and females. Both sexes were equally affected. The cuneate, gracile, and cochlear nuclei and the cerebellar white matter (rostral vermis) were the most common locations for AD. Incidence of AD increased with age in the cuneate nucleus, cerebellar white matter (rostral vermis), trigeminal nuclei/tracts, and lumbar spinal cord. Axonal dystrophy in the CNS was not accompanied by neuronal degeneration/necrosis, nerve fiber degeneration, and/or glial reaction. Axonal dystrophy was not observed in the PNS (sciatic nerve, vagus nerve branches, or gastrointestinal mural autonomic plexuses).

Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia

The dorsal horns of the spinal cord and the trigeminal nuclei in the brainstem contain neuron populations that are critical to process sensory information. Neurons in these areas are highly heterogeneous in their morphology, molecular phenotype and intrinsic properties, making it difficult to identify functionally distinct cell populations, and to determine how these are engaged in pathophysiological conditions. There is a growing consensus concerning the classification of neuron populations, based on transcriptomic and transductomic analyses of the dorsal horn. These approaches have led to the discovery of several molecularly defined cell types that have been implicated in cutaneous mechanical allodynia, a highly prevalent and difficult-to-treat symptom of chronic pain, in which touch becomes painful. The main objective of this review is to provide a contemporary view of dorsal horn neuronal populations, and describe recent advances in our understanding of on how they participate in cutaneous mechanical allodynia.

Genetic Deletion of TrpV1 and TrpA1 Does not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

ABSTRACTExposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similarly to wildtype mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford et. al 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in wildtype (WT) and TrpA1/V1 double KO (TRPA1/V1Db1-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, 30 mM citric acid, along with 100 μM SC45647 and H2O. Both WT and TRPA1/V1Db1-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36 respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Db1-/-animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.