In nicotinic acetylcholine receptors (nAChR), as well as glycine, GABAA (gamma-aminobutyric acid), serotonin (5-HT3), and GluCl glutamate receptors, a leucine residue at the approximate midpoint of the M2 transmembrane domain (the 9' position) is conserved across most known subunits. Structural data for the nAChR suggest that the Leu 9' residues occupy a 'kink' in each of the five M2 helices and point into the closed channel; in the opening step, the M2 helices rotate so that Leu 9' side chains no longer occlude the conduction pathway. Mutation of Leu 9' to one of several other residues slows desensitization and increases sensitivity to agonist. We have exploited the alpha 2 beta gamma delta stoichiometry of muscle nAChR to express receptors with ms* = 0 to 5 Leu 9'Ser mutated subunits. Strikingly, each Leu 9'Ser mutation shifts the dose-response relation for ACh to the left by approximately 10-fold; a nAChR with ms* = 4 is 10(4)-fold more sensitive than the wild type. The results suggest that each of the five Leu 9' residues participates independently and symmetrically in a key step in the structural transition between the closed and open states.

The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+-dependent homophilic interactions between cells and transduce signals by interacting with cytoplasmic proteins. In the hippocampus, immunostaining combined with confocal microscopy revealed that both neural- (N-) and epithelial- (E-) cadherin are present at synaptic sites, implying a role in synaptic function. Pretreatment of hippocampal slices with antibodies (Abs) raised against the extracellular domain of either N-cad or E-cad had no effect on basal synaptic properties but significantly reduced long-term potentiation (LTP). Infusion of antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization also attenuated LTP induction without affecting previously established LTP. Because the intense synaptic stimulation associated with LTP induction might transiently deplete extracellular Ca2+ and hence potentially destabilize cadherin-cadherin interactions, we examined whether slices could be protected from inhibition by N-cad Abs or HAV peptides by raising the extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+ prevented the block of LTP by these agents. Taken together, these results indicate that cadherins are involved in synaptic plasticity, and the stability of cadherin-cadherin bonds may be regulated by synaptic stimulation.

Abundant evidence from previous fMRI studies on acupuncture has revealed significant modulatory effects at widespread brain regions. However, few reports on the modulation to the default mode network (DMN) of stroke patients have been investigated in the field of acupuncture. To study the modulatory effects of acupuncture on the DMN of stroke patients, eight right hemispheric infarction and stable ischemic stroke patients and ten healthy subjects were recruited to undergo resting state fMRI scanning before and after acupuncture stimulation. Functional connectivity analysis was applied with the bilateral posterior cingulate cortices chosen as the seed regions. The main finding demonstrated that the interregional interactions between the ACC and PCC especially enhanced after acupuncture at GB34 in stroke patients, compared with healthy controls. The results indicated that the possible mechanisms of the modulatory effects of acupuncture on the DMN of stroke patients could be interpreted in terms of cognitive ability and motor function recovery.

Stroke is a leading cause of motor disability. Acupuncture is an effective therapeutic strategy for poststroke motor impairment. However, its mechanism is still elusive. Twenty-two stroke patients having a right-hemispheric subcortical infarct and 22 matched healthy controls were recruited to undergo diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scanning. The resting-state fMRI was implemented before and after needling at GB34 (Yanglingquan). The stroke patients presented a substantially reduced fractional anisotropy value in the right superior longitudinal fasciculus (SLF), corticospinal tract, and corpus callosum. The structural integrity of the frontoparietal part of the SLF (SLF-FP) correlated with the motor scores of lower limbs in stroke patients. This corticocortical association bundle originated from the premotor cortex (PM) and the adjacent supplementary motor area (SMA), known as secondary motor areas, and terminated in the supramarginal gyrus (SMG). After acupuncture intervention, the corresponding functional connectivity between the PM/SMA and SMG was enhanced in stroke patients compared with healthy controls. These findings suggested that the integrity of the SLF is a potential neuroimaging biomarker for motor disability of lower limbs following a stroke. Acupuncture could increase the communication between the cortices connected by the impaired white matter tracts, implying the neural mechanism underlying the acupuncture intervention.