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Abstract O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.

Abstract Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling. Accumulating evidence has revealed that spinal astrocytes are involved in pathological pain by modulating the efficacy of neurotransmitters such as glutamate and GABA through transporters located in the PAP and by directly regulating synaptic transmission through various gliotransmitters. Although various CAMs contribute to pathological pain, insufficient evidence is available as to whether astrocytic CAMs also have this role. Therefore, more in-depth research is needed on how pathological pain is induced and maintained by astrocytes, especially in the PAP surrounding the synapse, and this will subsequently increase our understanding and treatment of pathological pain.

Abstract Itch is a distinctive sensation that causes a specific affection and scratching reaction. The anterior cingulate cortex (ACC) has been linked to itch sensation in numerous studies; however, its precise function in processing pruritic inputs remains unknown. Distinguishing the precise role of the ACC in itch sensation can be challenging because of its capacity to conduct heterologous neurophysiological activities. Here, we used in vivo calcium imaging to examine how ACC neurons in free-moving mice react to pruritogenic histamine. In particular, we focused on how the activity of the ACC neurons varied before and after the scratching response. We discovered that although the change in neuronal activity was not synchronized with the scratching reaction, the overall activity of itch-responsive neurons promptly decreased after the scratching response. These findings suggest that the ACC does not directly elicit the feeling of itchiness.

Abstract Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injection enhances Fos (+) cells in posterior portion within parvocellular and central subnuclei of the medial division (LHbM) of the LHb. Moreover, chemogenetic suppression of LHbM reduced scratching behavior induced by histamine injection. These results suggest that LHb is required for processing itch information to induce histaminergic itchy response.

Abstract Synaptic proteins play an important role for the regulation of synaptic plasticity. Numerous studies have identified and revealed individual synaptic protein functions using protein overexpression or deletion. In neuropathic pain nociceptive stimuli conveyed from the periphery repetitively stimulate neurons in the central nerve system, brain and spinal cord. Neuronal activities change the turnover (synthesis and degradation) rate of synaptic proteins. Thus, the analysis of synaptic protein turnover rather than just expression level change is critical for studying the role of synaptic proteins in synaptic plasticity. Here, we analyzed synaptosomal proteome in the anterior cingulate cortex (ACC) to identify protein turnover rate changes caused by peripheral nerve injury. Whereas PKCγ levels were not altered, we found that the protein’s turnover rate decreased after peripheral nerve injury. Our results suggest that postsynaptic PKCγ synthesized by neuronal activities in the ACC is translocated to the postsynaptic membrane with an extended half-life.