A Learning Experience

Abstract

A mind that is stretched by a new experience can never go back to its old dimensions. - Oliver Wendell Holmes, Jr. Central to survival is the ability to appropriately sense, interpret and respond to stimuli from the environment. This is largely the work of the nervous and immune systems, which are capable not only of recognition and response, but also of adaptation via memory formation at both system and cellular scales. Research at the interface of neuroscience and immunology has revealed reciprocal interactions between these two systems. In coordinated Special Issues, Trends in Neurosciences and Trends in Immunology explore how these neuroimmune interactions build and maintain system homeostasis, as well as influence what happens in disease and normal aging. We approach these topics from different perspectives with the joint aim of highlighting the many levels of interaction between these two systems, and the exciting questions that lie at this intersection. The Trends in Immunology issue focuses on neuroimmune interactions at a cellular level, both in the CNS and in the periphery. We review recent advances in our understanding of how immune cells survey the CNS for the presence of pathogens, tissue damage or degeneration, and discuss the importance of this surveillance for the maintenance of CNS homeostasis, revisiting also in this context the concept of CNS immune privilege. The immune system responds differently to infection and to sterile injury. We consider the mechanisms involved in discriminating between these types of challenges, and how these ultimately lead to damage control and tissue repair. Microglia are central to CNS immune surveillance and to the establishment and protection of CNS integrity. Articles in the issue discuss how the roles played by microglia change with the maturing CNS, from the active shaping of developing neuronal networks during embryogenesis to surveillance for degeneration and resolution of damage in adulthood. The authors consider the implications of malfunction of these processes in light of recent findings that have revealed roles for microglia in learning and memory via the regulation of synaptic plasticity. We review evidence indicating distinct origins for microglia during embryogenesis and in response to injury in adulthood, and discuss how origin relates to function and to the permanence of these cells in the CNS. The immune response in the CNS often involves the recruitment of T cells from the periphery; we discuss the impact of the arrival of these cells to the local inflammatory milieu, and examine their contribution to CNS pathology, such as in the case of multiple sclerosis. Moving beyond the CNS, we examine the contribution of the somatosensory system to the deployment of immune responses in barrier tissues, and discuss also how certain immune cells subsets impact homeostatic neural circuits, such as those associated with metabolism. The Trends in Neurosciences issue in turn moves the discussion to the roles of neuroimmune interactions in normal and pathological cognition and behavior. Articles in the issue examine the similar part that sleep plays in a critical function of the CNS and immune systems, and the roles of inflammation and various immune cell subsets in neurological and psychiatric disease. In this context, roadblocks to devising and delivering novel therapies for these conditions are discussed and new approaches are considered. Memory consolidation - the transformation of new, labile, memories into stable, long-lasting, representations - is a key feature of both psychological and immunological memory. Born and colleagues argue that, via common physiological mechanisms, sleep plays a central role in consolidation of both psychological and immunological memory. Learning and memory, as well as decision-making, motivation and emotional regulation are severely disrupted in many conditions that exhibit both CNS and immune pathology. Articles by Meyer-Luehmann and Prinz and Andreasson and colleagues examine the contribution of various subsets of CNS myeloid cells to Alzheimer's disease, Godbout et al look at the role of primed microglia in traumatic brain injury, and Yirmiya discusses evidence that major depression should be considered primarily a microglial disease. Finally, identification of novel targets and development of new drugs to treat all of these conditions are urgently needed to ease the considerable burden these diseases represent to patients, families and societies. Chow and Gu discuss recent progress in determining the molecular regulators of blood-brain barrier development and function and the importance of understanding these pathways for identification of novel drug targets and development of new therapies. We would like to thank the distinguished experts who contributed their time and effort as authors and reviewers to make these two Special Issues timely and thought provoking. A new research frontier is being presented – one that asks us to consider multi-level interactions of two complex systems that shape not only health but also behavior. The articles in these issues outline many open questions that lie at the intersection of immunity and neuroscience, and the opportunities that this further understanding may bring to the treatment of devastating diseases. Addressing these questions will require not only advanced approaches and technologies, but also broadened perspectives that bridge immunology and neuroscience. We hope that these issues present a start on this path for many young researchers, and continued inspiration for those already leading the way. Enjoy!