Thalamocortical Spectral Transmission Relies on Balanced Input Strengths

The thalamus is a key element of sensory transmission in the brain, as it gates and selects sensory streams through a modulation of its internal activity. A preponderant role in these functions is played by its internal activity in the alpha range ([8–14] Hz), but the mechanism underlying this process is not completely understood. In particular, how do thalamocortical connections convey stimulus driven information selectively over the back-ground of thalamic internally generated activity? Here we investigate this issue with a spiking network model of feedforward connectivity between thalamus and primary sensory cortex reproducing the local field potential of both areas. We found that in a feedforward network, thalamic oscillations in the alpha range do not entrain cortical activity for two reasons: (i) alpha range oscillations are weaker in neurons projecting to the cortex, (ii) the gamma resonance dynamics of cortical networks hampers oscillations over the 10–20 Hz range thus weakening alpha range oscillations. This latter mechanism depends on the balance of the strength of thalamocortical connections toward excitatory and inhibitory neurons in the cortex. Our results highlight the relevance of corticothalamic feedback to sustain alpha range oscillations and pave the way toward an integrated understanding of the sensory streams traveling between the periphery and the cortex.

Growth and Survival of Satellite Glial Cells in Different Culture Supplementations

Background: In dorsal root ganglion (DRG), satellite glial cells (SGCs) tightly surrounded neurons and modulated microenvironment and sensory transmission. However, the biological properties of primary SGCs in culture were not fully understood. In the present study, we provided a method to harvest abundant and high-purity SGCs from neonatal rats. Three supplementations containing Dulbecco’s Modified Eagle Medium (DMEM)/F12, DMEM high glucose (HG) and Neurobasal-A (NB) were used to evaluate SGCs growth and survival in culture. Results: CCK-8 proliferation assay showed the increased proliferation in DMEM/F12 and DMEM/HG, but not in NB medium. NB medium caused cell death indicated by Bax, AnnexinV and PI staining. Glutamine was the major nutrition source for SGCs in culture and its exogenous application improved the poor proliferation and severe cell death in NB medium. SGCs markers GS and GFAP were similar in three supplementations and intensively expressed in culture. Differently, GS but not GFAP was remarkable in the intact DRG under normal condition. Conclusions: These results suggested that SGCs growth in culture depended on time and culture supplementation and DMEM/F12 medium was recommended to get high-purity SGCs. Glutamine was the major nutrition and the key molecule to maintain cell growth and survival in culture. Our study shed a new light on understanding the biological property and modulation of glial cells in the peripheral sensory ganglia.

Sensory Transmission is Bi-directionally Modulated by Astrocytic Ca2+ in Barrel Cortex of Behaving Mice

Different effects of astrocyte during sleep and awake have been extensively studied, especially for metabolic clearance by the glymphatic system, which works during sleep and stops working during waking states. However, how astrocytes contribute to modulation of sensory transmission during sleep and awake animals remain largely unknown. Recent advances in genetically encoded Ca2+ indicators have provided a wealth of information on astrocytic Ca2+, especially in their fine perisynaptic processes, where astrocytic Ca2+ most likely affects the synaptic function. Here we use two-photon microscopy to image astrocytic Ca2+ signaling in freely moving mice trained to run on a wheel in combination with in vivo whole-cell recordings to evaluate the role of astrocytic Ca2+ signaling in different behavior states. We found that there are two kinds of astrocytic Ca2+ signaling: a small long-lasting Ca2+ increase during sleep state and a sharp widespread but short-long-lasting Ca2+ spike when the animal was awake (fluorescence increases were 23.2 ± 14.4% for whisker stimulation at sleep state, compared with 73.3 ± 11.7% for at awake state, paired t-test, p < 0.01). The small Ca2+ transients decreased extracellular K+, hyperpolarized the neurons, and suppressed sensory transmission; while the large Ca2+ wave enhanced sensory input, contributing to reliable sensory transmission in aroused states. Locus coeruleus activation works as a switch between these two kinds of astrocytic Ca2+ elevation. Thus, we show that cortical astrocytes play an important role in processing of sensory input. These two types of events appear to have different pharmacological sources and may play a different role in facilitating the efficacy of sensory transmission.

Nodal GABA facilitates axon spike transmission in the spinal cord

SUMMARYGABA is an inhibitory neurotransmitter that produces both postsynaptic and presynaptic inhibition. We describe here an opposing excitatory action of GABA that facilitates spike transmission at nodes of Ranvier in myelinated sensory axons in the spinal cord. This nodal facilitation results from axonal GABAA receptors that depolarize nodes toward threshold, enabling spike propagation past the many branch points that otherwise fail, as observed in spinal cords isolated from mice or rats. Activation of GABAergic neurons, either directly with optogenetics or indirectly with cutaneous stimulation, caused nodal facilitation that increased sensory transmission to motoneurons without postsynaptically exciting motoneurons. This increased transmission with optogenetic or cutaneous stimulation also occurred in awake mice and humans. Optogenetic inhibition of GABAergic neurons decreased sensory transmission, implying that axonal conduction relies on GABA. The concept of nodal facilitation likely generalizes to other large axons in the CNS, enabling recruitment of selective branches and functional pathways.

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Background Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. Methods We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. Results We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). Conclusion These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.

Neuropathic Itch

Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.

Thalamocortical spectral transmission relies on balanced input strengths

The thalamus is a key element of sensory transmission in the brain, as all sensory information is processed by the thalamus before reaching the cortex. The thalamus is known to gate and select sensory streams through a modulation of its internal activity in which spindle oscillations play a preponderant role, but the mechanism underlying this process is not completely understood. In particular, how do thalamocortical connections convey stimulus-driven information selectively over the background of thalamic internally generated activity (such as spindle oscillations)? Here we investigate this issue with a spiking network model of connectivity between thalamus and primary sensory cortex reproducing the local field potential of both areas. We found two features of the thalamocortical dynamics that filter out spindle oscillations: i) spindle oscillations are weaker in neurons projecting to the cortex, ii) the resonance dynamics of cortical networks selectively blocks frequency in the range encompassing spindle oscillations. This latter mechanism depends on the balance of the strength of thalamocortical connections toward excitatory and inhibitory neurons in the cortex. Our results pave the way toward an integrated understanding of the sensory streams traveling between the periphery and the cortex.