The Journal of neuroscience : the official journal of the Society for Neuroscience
-
In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. ⋯ Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression.
-
Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. ⋯ However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.
-
Itch is an unpleasant sensation that initiates scratching behavior. The itch-scratch reaction is a complex phenomenon that implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch-scratch processes are poorly understood. ⋯ Manipulation of ACC-DMS projections has no effect on acute pain sensation. Furthermore, the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons. Understanding the supraspinal itch circuits is of great significance in the development of new therapies for chronic itch-related intractable diseases.
-
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. ⋯ Kv3.4 channels are ubiquitously expressed in the dorsal root ganglion (DRG), where they are major regulators of DRG excitability. However, little is known about the ionic mechanisms that regulate nociceptive synaptic transmission at the level of the first synapse in the spinal cord, which is critical to pain transmission in both intact and pathological states. Here, we show that Kv3.4 channels have a significant impact on glutamatergic synaptic transmission in the dorsal horn, further illuminating its potential as a molecular pain therapeutic target.
-
Chronic cerebral hypoperfusion is a characteristic seen in widespread CNS diseases, including neurodegenerative and mental disorders, and is commonly accompanied by cognitive impairment. Recently, several studies demonstrated that chronic cerebral hypoperfusion can induce the excessive inflammatory responses that precede neuronal dysfunction; however, the precise mechanism of cognitive impairment due to chronic cerebral hypoperfusion remains unknown. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable channel that is abundantly expressed in immune cells and is involved in aggravation of inflammatory responses. ⋯ SIGNIFICANCE STATEMENT Chronic cerebral hypoperfusion is manifested in a wide variety of CNS diseases, including neurodegenerative and mental disorders that are accompanied by cognitive impairment; however, the underlying mechanisms require clarification. Here, we used a chronic cerebral hypoperfusion mouse model to investigate whether TRPM2, a Ca2+-permeable cation channel highly expressed in immune cells, plays a destructive role in the development of chronic cerebral hypoperfusion-induced cognitive impairment, and propose a new hypothesis in which TRPM2-mediated activation of microglia, not macrophages, specifically contributes to the pathology through the aggravation of inflammatory responses. These findings shed light on the understanding of the mechanisms of chronic cerebral hypoperfusion-related inflammation, and are expected to provide a novel therapeutic molecule for cognitive impairment in CNS diseases.