Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

The Enteropathogenic E. coli (EPEC) Tir Effector Inhibits NF-κB Activity by Targeting TNFα Receptor-Associated Factors

Enteropathogenic Escherichia coli (EPEC) disease depends on the transfer of effector proteins into epithelia lining the human small intestine. EPEC E2348/69 has at least 20 effector genes of which six are located with the effector-delivery system genes on the Locus of Enterocyte Effacement (LEE) Pathogenicity Island. Our previous work implied that non-LEE-encoded (Nle) effectors possess functions that inhibit epithelial anti-microbial and inflammation-inducing responses by blocking NF-κB transcription factor activity. Indeed, screens by us and others have identified novel inhibitory mechanisms for NleC and NleH, with key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE-encoded Translocated-intimin receptor (Tir) effector has a potent and specific ability to inhibit NF-κB activation. Indeed, biochemical, imaging and immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir interaction with cytoplasm-located TNFα receptor-associated factor (TRAF) adaptor proteins induces their proteasomal-independent degradation. Infection studies support this Tir-TRAF relationship but reveal that Tir, like NleC and NleH, has a non-essential contribution in EPEC's NF-κB inhibitory capacity linked to Tir's activity being suppressed by undefined EPEC factors. Infections in a disease-relevant intestinal model confirm key NF-κB inhibitory roles for the NleB1/NleE1 effectors, with other studies providing insights on host targets. The work not only reveals a second Intimin-independent property for Tir and a novel EPEC effector-mediated NF-κB inhibitory mechanism but also lends itself to speculations on the evolution of EPEC's capacity to inhibit NF-κB function

Cyclin-Dependent Kinase 6 Phosphorylates NF-kappa B P65 at Serine 536 and Contributes to the Regulation of Inflammatory Gene Expression

Peer reviewe

Segregation of visceral and somatosensory afferents. An fMRI and cytoarchitectonic mapping study

Ano-rectal stimulation provides an important model for the processing of somatosensory and visceral sensations in the human nervous system. In spite of their anatomical proximity, the anal canal is innervated by somatosensory afferents whereas the rectum is innervated by the visceral nervous system. In a functional magnetic resonance (fMRI) experiment, we examined the cerebral responses to pneumatic balloon distension of these two structures to test whether somatosensory and visceral stimulation elicited distinct brain activations in spite of their spinal convergence. The specificity of the identified activations was analyzed by Bayesian mixed effects modeling. Activations in the parietal operculum were also compared to the location of cytoarchitectonically defined areas OP 1-4, which are part of the secondary somatosensory cortex (SII), to analyze whether the SII region was activated by anal and/or rectal stimulation. The lowest segregation between visceral and somatosensory stimuli was in the insular cortex, which supports the interpretation of the insula as an integrative region, receiving input from different sensory modalities. The most distinct segregation was found in the fronto-parietal operculum. Here the activations following anal and rectal stimulation were not only functionally but also anatomically distinct. Anal sensations were processed similar to other somatosensory stimuli in the SII cortex (area OP 4). Rectal afferents on the other hand were not processed in SII. Rather, they evoked activation at a more anterior location on the precentral operculum. These results demonstrate a functionally and anatomically distinct processing of somatosensory and visceral afferents in the human cerebral cortex

Cerebral Activation during Anal and Rectal Stimulation

While the rectum is innervated by visceral afferents, the anal canal is innervated by the somatosensory pudendal nerve. The representation of these two central domains of intestinal sensations in the human brain is largely unknown. Nonpainful pneumatic stimulation of the anal canal and the distal rectum using event-related functional magnetic resonance imaging (fMRI) was performed in eight healthy subjects. Subjective scaling of sensations revealed no differences in unpleasantness and pain during both stimuli. Both types of stimuli revealed fMRI activation in secondary somatosensory, insula, cingular gyrus, left inferior parietal, and right orbitofrontal cortex. Anal stimulation resulted in additional activation of primary sensory and motor cortex, supplementary motor area, and left cerebellum. We concluded that viscerorectal and somatosensory anal stimulation predominantly differ in their primary sensory activation and additional activation in motor areas. This motor response following aversive somatosensory stimuli may be caused by a reflexive avoidance reaction which is not observed after the more diffuse experienced visceral stimulation

Cortical processing of residual ano‐rectal sensation in patients with spinal cord injury: an fMRI study

Eleven paraplegic patients with complete traumatic spinal cord injuries (SCI) [according to American Spinal Injury Association (ASIA) criteria] at different levels (Th3–L3) were investigated during non‐painful stimulation of the distal rectum and anal canal, using event related functional magnetic resonance imaging. Although a complete lesion was clinically diagnosed in all, four of them experienced reproducible sensations during anal and/or rectal stimulation. In six patients, individual data analysis revealed significant activation in the right secondary somatosensory cortex SII, the posterior cingular gyrus, the prefrontal cortex, and the left posterior cerebellar lobe during either anal or rectal stimulation or both. A Region of interest analysis using a data mask from healthy controls confirmed that SCI patients demonstrate cortical activation in areas similar to those activated in healthy volunteers, but to a less extensive degree. This supports the notion that the diagnosis of complete spinal cord transsection by ASIA criteria alone may be insufficient for assessment of ‘completeness’ of cord lesions, and that visceral sensitivity testing may be required in addition