Descending Modulation of Spinal Itch Transmission by Primary Somatosensory Cortex.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu ZH
PROVIDER: S-EPMC8423972 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Descending Modulation of Spinal Itch Transmission by Primary Somatosensory Cortex.
Wu Zi-Han ZH Shao Han-Yu HY Fu Yuan-Yuan YY Wu Xiao-Bo XB Cao De-Li DL Yan Sheng-Xiang SX Sha Wei-Lin WL Gao Yong-Jing YJ Zhang Zhi-Jun ZJ
Neuroscience bulletin 20210531 9
Similar Datasets
Project description:Multiple cortical areas including the primary somatosensory cortex (S1) are activated during itch signal processing, yet cortical representation of itch perception remains unknown. Using novel miniature two-photon microscopic imaging in free-moving mice, we investigated the coding of itch perception in S1. We found that pharmacological inactivation of S1 abolished itch-induced scratching behavior, and the itch-induced scratching behavior could be well predicted by the activity of a fraction of layer 2/3 pyramidal neurons, suggesting that a subpopulation of S1 pyramidal neurons encoded itch perception, as indicated by immediate subsequent scratching behaviors. With a newly established optogenetics-based paradigm that allows precisely controlled pruritic stimulation, we found that a small fraction of S1 neurons exhibited an ignition-like pattern at the detection threshold of itch perception. Our study revealed the neural mechanism underlying itch perceptual coding in S1, thus paving the way for the study of cortical representation of itch perception at the single-neuron level in freely moving animals.
| S-EPMC9232292 | biostudies-literature
Project description:Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ventromedial medulla (RVM) has been the most studied, whereas little is known about direct corticospinal modulation. Here, we found that stimulation in the anterior cingulate cortex (ACC) potentiated spinal excitatory synaptic transmission and this modulation is independent of the RVM. Peripheral nerve injury enhanced the spinal synaptic transmission and occluded the ACC-spinal cord facilitation. Inhibition of ACC reduced the enhanced spinal synaptic transmission caused by nerve injury. Finally, using optogenetics, we showed that selective activation of ACC-spinal cord projecting neurons caused behavioral pain sensitization, while inhibiting the projection induced analgesic effects. Our results provide strong evidence that ACC stimulation facilitates spinal sensory excitatory transmission by a RVM-independent manner, and that such top-down facilitation may contribute to the process of chronic neuropathic pain.
| S-EPMC5951839 | biostudies-literature
Project description:A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11-SDH) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1+) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor-expressing (GRPR+) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch.
| S-SCDT-10_15252-EMBR_202256098 | biostudies-other
Project description:Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.
| S-EPMC2481381 | biostudies-literature
Project description:Axonal patches are known as the major sites of synaptic connections in the cerebral cortex of higher order mammals. However, the functional role of these patches is highly debated. Patches are formed by populations of nearby neurons in a topographic manner and are recognized as the termination fields of long-distance lateral connections within and between cortical areas. In addition, axons form numerous boutons that lie outside the patches, whose function is also unknown. To better understand the functional roles of these two distinct populations of boutons, we compared individual and collective morphological features of axons within and outside the patches of intra-areal, feedforward, and feedback pathways by way of tract tracing in the somatosensory cortex of New World monkeys. We found that, with the exception of tortuosity, which is an invariant property, bouton spacing and axonal convergence properties differ significantly between axons within patch and no-patch domains. Principal component analyses corroborated the clustering of axons according to patch formation without any additional effect by the type of pathway or laminar distribution. Stepwise logistic regression identified convergence and bouton density as the best predictors of patch formation. These findings support that patches are specific sites of axonal convergence that promote the synchronous activity of neuronal populations. On the other hand, no-patch domains could form a neuroanatomical substrate to diversify the responses of cortical neurons.
| S-EPMC9305200 | biostudies-literature
Project description:In humans, gamma-band oscillations in the primary somatosensory cortex (S1) correlate with subjective pain perception. However, functional contributions to pain and the nature of underlying circuits are unclear. Here we report that gamma oscillations, but not other rhythms, are specifically strengthened independently of any motor component in the S1 cortex of mice during nociception. Moreover, mice with inflammatory pain show elevated resting gamma and alpha activity and increased gamma power in response to sub-threshold stimuli, in association with behavioral nociceptive hypersensitivity. Inducing gamma oscillations via optogenetic activation of parvalbumin-expressing inhibitory interneurons in the S1 cortex enhances nociceptive sensitivity and induces aversive avoidance behavior. Activity mapping identified a network of prefrontal cortical and subcortical centers whilst morphological tracing and pharmacological studies demonstrate the requirement of descending serotonergic facilitatory pathways in these pain-related behaviors. This study thus describes a mechanistic framework for modulation of pain by specific activity patterns in the S1 cortex.
| S-EPMC6395755 | biostudies-literature
Project description:Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior. Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca(2+) transients, and action potential firing of GRPR(+) neurons. Immunostaining, biochemical, and biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes. Furthermore, 5-HT1A blockade significantly attenuates, whereas its activation contributes to, long-lasting itch transmission. Thus, our studies demonstrate that the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outputs, and a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy.Video abstract
| S-EPMC4254557 | biostudies-literature
Project description:Primary sensory cortex is thought to process incoming sensory information, while decision variables important for driving behavior are assumed to arise downstream in the processing hierarchy. Here, we used population two-photon calcium imaging and targeted two-photon optogenetic stimulation of neurons in layer 2/3 of mouse primary somatosensory cortex (S1) during a texture discrimination task to test for the presence of decision signals and probe their behavioral relevance. Small but distinct populations of neurons carried information about the stimulus irrespective of the behavioral outcome (stimulus neurons), or about the choice irrespective of the presented stimulus (decision neurons). Decision neurons show categorical coding that develops during learning, and lack a conclusive decision signal in Miss trials. All-optical photostimulation of decision neurons during behavior improves behavioral performance, establishing a causal role in driving behavior. The fact that stimulus and decision neurons are intermingled challenges the idea of S1 as a purely sensory area, and causal perturbation suggests a direct involvement of S1 decision neurons in the decision-making process.
| S-EPMC7613627 | biostudies-literature
Project description:Another person's caress is one of the most powerful of all emotional social signals. How much the primary somatosensory cortices (SIs) participate in processing the pleasantness of such social touch remains unclear. Although ample empirical evidence supports the role of the insula in affective processing of touch, here we argue that SI might be more involved in affective processing than previously thought by showing that the response in SI to a sensual caress is modified by the perceived sex of the caresser. In a functional MRI study, we manipulated the perceived affective quality of a caress independently of the sensory properties at the skin: heterosexual males believed they were sensually caressed by either a man or woman, although the caress was in fact invariantly delivered by a female blind to condition type. Independent analyses showed that SI encoded, and was modulated by, the visual sex of the caress, and that this effect is unlikely to originate from the insula. This suggests that current models may underestimate the role played by SI in the affective processing of social touch.
| S-EPMC3382530 | biostudies-literature
Project description:Neuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher central nervous system areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK + S1-corticospinal tract [CST] neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+ S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. Wheat germ agglutinin-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.
| S-EPMC8152836 | biostudies-literature