Synesthesia is a phenomenon in which an experience in one domain is accompanied by an involuntary secondary experience in another, unrelated domain; in classical synesthesia, these associations are arbitrary and idiosyncratic. Cross-modal correspondences refer to universal associations between seemingly unrelated sensory features, e.g., auditory pitch and visual size. Some argue that these phenomena form a continuum, with classical synesthesia being an exaggeration of universal cross-modal correspondences, whereas others contend that the two are quite different, since cross-modal correspondences are non-arbitrary, non-idiosyncratic, and do not involve secondary experiences. Here, we used the implicit association test to compare sy nesthetes’ and non-synesthetes’ sensitivity to cross-modal correspondences. We tested the associations between auditory pitch and visual elevation, auditory pitch and visual size, and sound-symbolic correspondences between auditory pseudowords and visual shapes. Synesthetes were more sensitive than non-synesthetes to cross-modal correspondences involving sound-symbolic, but not low-level sensory, associations. We conclude that synesthesia heightens universally experienced cross-modal correspondences, but only when these involve sound symbolism. This is only partly consistent with the idea of a continuum between synesthesia and cross-modal correspondences, but accords with the idea that synesthesia is a high-level, post-perceptual phenomenon, with spillover of the abilities of synesthetes into domains outside their synesthesias. To our knowledge, this is the first demonstration that synesthetes, relative to non-synesthetes, experience stronger cross-modal correspondences outside their synesthetic domains.
Mitochondria play a critical role in various pathways of regulated cell death. Here we propose a novel method for detection of initial derangement of mitochondria in degenerating and dying neuronal cells. The method is based on our recent finding that antibodies directed against the cannabinoid type 1 receptor (CB1) also bind the mitochondrial stomatin-like protein 2 (SLP2) that belongs to an inner mitochondrial membrane protein complex. It is well established that SLP2 regulates mitochondrial biogenesis and respiratory functions. We now show that anti-CB1 antibodies recognize conformational epitopes but not the linear amino acid sequence of SLP2. In addition we found that anti-CB1 serum mostly labels swollen mitochondria with early or advanced stages of pathology in mouse brain while other proteins of the complex may mask epitopes of SLP2 in the normal mitochondria. Although neurons and endothelial cells in healthy brains contain occasional immunopositive mitochondria detectable with anti-CB1 serum, their numbers increase significantly after hypoxic insults in parallel with signs of cellular damage. Moreover, use of electron microscopy suggests relocation of SLP2 from its normal functional position in the inner mitochondrial membrane into the mitochondrial matrix in pathological cells. Thus, SLP2-like immunolabeling serves as an in situ histochemical target detecting early derangement of mitochondria. Anti-CB1 serum is crucial for this purpose because available anti-SLP2 antibodies do not provide selective labeling of mitochondria in the fixed tissue. This new method of detecting mitochondrial dysfunction can benefit the in vitro research of human diseases and developmental disorders by enabling analysis in live animal models.
Enhancing the regeneration of axons is often considered to be a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients is explored. The rationale, effectiveness and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins and androgens are considered to be common requirements. Similarly, there are sex-specific requirements for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem to be ready to be translated to clinical use.