Bidirectional interactions between the immune system and central nervous system have been acknowledged for centuries. Over the past 100 years, pioneering studies in both animal models and humans have delineated the behavioral consequences of neuroimmune activation, including the different facets of sickness behavior. Rodent studies have uncovered multiple neural pathways and mechanisms that mediate anorexia, fever, sleep alterations, and social withdrawal following immune activation. Furthermore, work conducted in human patients receiving interferon treatment has elucidated some of the mechanisms underlying immune-induced behavioral changes such as malaise, depressive symptoms, and cognitive deficits. These findings have provided the foundation for development of treatment interventions for conditions in which dysfunction of immune-brain interactions leads to behavioral pathology. Rodent models of neuroimmune activation frequently utilize endotoxins and cytokines to directly stimulate the immune system. In the absence of pathogen-induced inflammation, a variety of environmental stressors, including psychosocial stressors, also lead to neuroimmune alterations and concurrent behavioral changes. These behavioral alterations can be assessed using a battery of behavioral paradigms while distinguishing acute sickness behavior from the type of behavioral outcome being assessed. Animal studies have also been useful in delineating the role of microglia, the neuroendocrine system, neurotransmitters, and neurotrophins in mediating the behavioral implications of altered neuroimmune activity. Furthermore, the timing and duration of neuroimmune challenge as well as the sex of the organism can impact the behavioral manifestations of altered neuroimmune activity. Finally, neuroimmune modulation through pharmacological or psychosocial approaches has potential for modulating behavior.
Gretchen N. Neigh, Mandakh Bekhbat, and Sydney A. Rowson
Sabra L. Klein and Jaclyn M. Schwarz
Sex is a biological variable that affects immune responses to both self and foreign antigens (e.g., microbial infections) in the central nervous system (CNS) as well as in peripheral organs. The sex of an individual is defined by the differential determination of the sex chromosomes, the organization of the reproductive organs, and the subsequent sex steroid hormone levels in males and females. Sex is distinct from gender, which includes self-identification as being a male or female as well as behaviors and activities that are determined by society or culture in humans. Male and female differences in immunological responses may be influenced by both sex and gender, with sex contributing to the physiological and anatomical differences that influence exposure, recognition, clearance, and even transmission of microbes in males and females. By contrast, gender may reflect behaviors that influence exposure to microbes, access to health care, or health-seeking behaviors that indirectly affect the course of infection in males and females. Though both sex and gender influence the immune response, the focus of this article is the biological factors that influence immunological differences between the sexes in both the CNS and peripheral tissues to alter the course of diseases across the life span.
Martha E. Bickford
Detailed studies of thalamic circuits have revealed many features that are shared across nuclei. For example, glutamatergic inputs to the thalamus can be placed into three categories based on the size of the synaptic terminals they form, their synaptic arrangements, and the postsynaptic responses they elicit. Remarkably, these three categories can be identified in most sensory nuclei of the dorsal thalamus. Likewise, in most sensory thalamic nuclei, circuits that release the neurotransmitter gamma aminobutyric acid (GABA) can be placed into two general categories based on their dendritic or axonal origins. Finally, similar cholinergic circuits have been identified across thalamic nuclei. The ultimate goal of examining the shared versus diverse features of thalamic circuits is to identify fundamental modules, mechanisms, and/or conceptual frameworks, in order to decipher thalamic function.
Kalynn Schulz, Marcia Chavez, and Arthur Castaneda
Nicotinic acetylcholine receptors (nAChRs) are present throughout the central nervous system and involved in a variety of physiological and behavioral functions. Nicotinic acetylcholine receptors are receptive to the presence of nicotine and acetylcholine and can be modulated through a variety of agonist and antagonist actions. These receptors are complex in their structure and function, and they are composed of multiple α and β subunits. Many affective disorders have etiological links with developmental exposure to the nAChR agonist nicotine. Given that abnormalities in nAChRs are associated with affective disorders such as depression and anxiety, pharmacological interventions targeting nAChRs may have significant therapeutic benefits.