Neuroscience
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Randomized Controlled Trial
Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.
Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. ⋯ We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioral symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders.
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Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. ⋯ Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process.
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Recent studies have revealed that the ventral premotor cortex (PMv) of nonhuman primates plays a pivotal role in various behaviors that require the transformation of sensory cues to appropriate actions. Examples include decision-making based on various sensory cues, preparation for upcoming motor behavior, adaptive sensorimotor transformation, and the generation of motor commands using rapid sensory feedback. Although the PMv has frequently been regarded as a single entity, it can be divided into at least five functionally distinct regions: F4, a dorsal convexity region immediately rostral to the primary motor cortex (M1); F5p, a cortical region immediately rostral to F4, lying within the arcuate sulcus; F5c, a ventral convexity region rostral to F4; and F5a, located in the caudal bank of the arcuate sulcus inferior limb lateral to F5p. ⋯ F5p contains "mirror neurons" to understand others' actions based on visual and other types of information, and F4d and F5p work together as a functional complex involved in controlling forelimb and eye movements, most efficiently in the execution and completion of coordinated eye-hand movements for reaching and grasping under visual guidance. In contrast, F5c and F5a are hierarchically higher than the F4d, F5p, and F5v complexes, and play a role in decision-making based on various sensory discriminations. Hence, the PMv subregions form a hierarchically organized integral system from decision-making to eye-hand coordination under various behavioral circumstances.
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The biological effects of the transcription factor NF-E2-related factor 2 (Nrf2) in acute peripheral nervous system (PNS) injury have not been adequately elucidated. By analyzing the results of Nrf2 knockout and Nrf2 activation experiments, we found the following: (1) the antioxidant system was rapidly inactivated after acute PNS injury in a partly Nrf2-dependent manner, giving rise to a temporary state of oxidative stress, and then slowly and partially recovered following regeneration. (2) Nrf2 knockout promoted the reprogramming and proliferation of Schwann cells and inhibited myelination, as well as the redifferentiation of repair Schwann cells. (3) Dimethyl fumarate had no influence on the myelination of regenerated nerves. (4) Nrf2 functional regulation was able to regulate the redox status of nerves by changing the levels of target antioxidants and reactive oxygen species (ROS) at the same time, without altering the balance between them. In conclusion, the Nrf2-antioxidant system was temporarily inactivated in injured nerves, promoting Schwann cell reprogramming and proliferation, and its functional recovery was essential for Schwann cell redifferentiation and myelination.
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The peripherally projecting axons of dorsal root ganglion (DRG) neurons readily regenerate after damage while their centrally projecting branches do not regenerate to the same degree after injury. One important reason for this inconsistency is the lack of pro-regeneration gene expression that occurs in DRG neurons after central injury relative to peripheral damage. The transcription factor SRY-box-containing gene 11 (Sox11) may be a crucial player in the regenerative capacity of axons as previous evidence has shown that it is highly upregulated after peripheral axon damage but not after central injury. ⋯ We found that Sox11 overexpression significantly enhanced neurite branching in vitro, and specifically induced the expression of glial cell line-derived neurotrophic factor (GDNF) family receptors, GFRα1 and GFRα3. The upregulation of these receptors by Sox11 overproduction altered the neurite growth patterns of DRG neurons alone and in response to growth factors GDNF and artemin; ligands for GFRα1 and GFRα3, respectively. These data support the role of Sox11 to promote neurite growth by altering responsiveness of neurotrophic factors and may provide mechanistic insight as to why peripheral axons of sensory neurons readily regenerate after injury, but the central projections do not have an extensive regenerative capacity.