The Class 3 Semaphorins (Sema3s) are a sub-family of proteins whose known biological roles are varied and growing. The mechanism of action of the Sema3s requires binding to transmembrane receptors that comprise heteromeric complexes of Neuropilins, Plexins and cell adhesion molecules (CAMs). However, knowledge of the receptor components of the Sema3s remains incomplete, and there may be receptor components which are yet undiscovered. The receptor complexes of the Sema3s share receptor components with each other, and it is the specific combination of these components within a heteromeric complex that is thought to give rise to selective binding and signalling for individual Sema3s. This crosstalk makes it experimentally difficult to define a single holoreceptor for each Sema3. Furthermore, the receptor composition for a given Sema3 may differ between cell types, and change as a function of developmental state or pathological situation. Nevertheless, there are at least some known differences in the constitutive structure of the receptors for the Sema3s. For example in neural cells, Sema3a and Sema3f signal through different Neuropilins (Nrp1 and Nrp2 respectively) and L1cam only appears important for Sema3a signaling, while Nrcam forms a complex with Nrp2. Further complexity arises from crosstalk of other families of ligands (e.g. VEGF) with Sema3 receptor components. Thus the Sema3s, which have been shown as antagonists for each other, can also act as antagonists for other families of molecules. This review compiles experimental evidence describing the receptor components for the Sema3s, detailing the current state of knowledge of which components are important for signaling of each Sema3 before going on to consider possible future directions for the field.

The human species possesses two complementary, yet distinct, universal communication systems—language and music. Functional imaging studies have revealed that some core elements of these two systems are processed in closely related brain regions, but there are also clear differences in brain circuitry that likely underlie differences in functionality. Music affects many aspects of human behavior, especially in encouraging prosocial interactions and promoting trust and cooperation within groups of culturally compatible but not necessarily genetically related individuals. Music, presumably via its impact on the limbic system, is also rewarding and motivating, and music can facilitate aspects of learning and memory. In this review these special characteristics of music are considered in light of recent research on the neuroscience of the peptide oxytocin, a hormone that has both peripheral and central actions, that plays a role in many complex human behaviors, and whose expression has recently been reported to be affected by music-related activities. I will first briefly discuss what is currently known about the peptide’s physiological actions on neurons and its interactions with other neuromodulator systems, then summarize recent advances in our knowledge of the distribution of oxytocin and its receptor (OXTR) in the human brain. Next, the complex links between oxytocin and various social behaviors in humans are considered. First, how endogenous oxytocin levels relate to individual personality traits, and then how exogenous, intranasal application of oxytocin affects behaviors such as trust, empathy, reciprocity, group conformity, anxiety, and overall social decision making under different environmental conditions. It is argued that many of these characteristics of oxytocin biology closely mirror the diverse effects that music has on human cognition and emotion, providing a link to the important role music has played throughout human evolutionary history and helping to explain why music remains a special prosocial human asset. Finally, it is suggested that there is a potential synergy in combining oxytocin- and music-based strategies to improve general health and aid in the treatment of various neurological dysfunctions.

In modern times there is increasing acceptance that music-based interventions are useful aids in the clinical treatment of a range of neurological and psychiatric conditions, including helping to reduce the perception of pain. Indeed, the belief that music, whether listening or performing, can alter human pain experiences has a long history, dating back to the ancient Greeks, and its potential healing properties have long been appreciated by indigenous cultures around the world. The subjective experience of acute or chronic pain is complex, influenced by many intersecting physiological and psychological factors, and it is therefore to be expected that the impact of music therapy on the pain experience may vary from one situation to another, and from one person to another. Where pain persists and becomes chronic, aberrant central processing is a key feature associated with the ongoing pain experience. Nonetheless, beneficial effects of exposure to music on pain relief have been reported across a wide range of acute and chronic conditions, and it has been shown to be effective in neonates, children and adults. In this comprehensive review we examine the various neurochemical, physiological and psychological factors that underpin the impact of music on the pain experience, factors that potentially operate at many levels – the periphery, spinal cord, brainstem, limbic system and multiple areas of cerebral cortex. We discuss the extent to which these factors, individually or in combination, influence how music affects both the quality and intensity of pain, noting that there remains controversy about the respective roles that diverse central and peripheral processes play in this experience. Better understanding of the mechanisms that underlie music’s impact on pain perception together with insights into central processing of pain should aid in developing more effective synergistic approaches when music therapy is combined with clinical treatments. The ubiquitous nature of music also facilitates application from the therapeutic environment into daily life, for ongoing individual and social benefit.

We used morphological, immunohistochemical and functional assessments to determine the impact of genetically-modified peripheral nerve (PN) grafts on axonal regeneration after injury. Grafts were assembled from acellular nerve sheaths repopulated ex vivo with Schwann cells (SCs) modified to express brain-derived neurotrophic factor (BDNF), a secretable form of ciliary neurotrophic factor (CNTF), or neurotrophin-3 (NT3). Grafts were used to repair unilateral 1 cm defects in rat peroneal nerves and 10 weeks later outcomes were compared to normal nerves and various controls: autografts, acellular grafts and grafts with unmodified SCs. The number of regenerated βIII-Tubulin positive axons was similar in all grafts with the exception of CNTF, which contained the fewest immunostained axons. There were significantly lower fiber counts in acellular, untransduced SC and NT3 groups using a PanNF antibody, suggesting a paucity of large caliber axons. In addition, NT3 grafts contained the greatest number of sensory fibres, identified with either IB₄ or CGRP markers. Examination of semi- and ultra-thin sections revealed heterogeneous graft morphologies, particularly in BDNF and NT3 grafts in which the fascicular organization was pronounced. Unmyelinated axons were loosely organized in numerous Remak bundles in NT3 grafts, while the BDNF graft group displayed the lowest ratio of umyelinated to myelinated axons. Gait analysis revealed that stance width was increased in rats with CNTF and NT3 grafts, and step length involving the injured left hindlimb was significantly greater in NT3 grafted rats, suggesting enhanced sensory sensitivity in these animals. In summary, the selective expression of BDNF, CNTF or NT3 by genetically modified SCs had differential effects on PN graft morphology, the number and type of regenerating axons, myelination, and locomotor function.