101-120 of 152 Results

Article

Tamar Makin and London Plasticity Lab

Phantom sensations are experienced by almost every person who has lost their hand in adulthood. This mysterious phenomenon spans the full range of bodily sensations, including the sense of touch, temperature, movement, and even the sense of wetness. For a majority of upper-limb amputees, these sensations will also be at times unpleasant, painful, and for some even excruciating to the point of debilitating, causing a serious clinical problem, termed phantom limb pain (PLP). Considering the sensory organs (the receptors in the skin, muscle or tendon) are physically missing, in order to understand the origins of phantom sensations and pain the potential causes must be studied at the level of the nervous system, and the brain in particular. This raises the question of what happens to a fully developed part of the brain that becomes functionally redundant (e.g. the sensorimotor hand area after arm amputation). Relatedly, what happens to the brain representation of a body part that becomes overused (e.g. the intact hand, on which most amputees heavily rely for completing daily tasks)? Classical studies in animals show that the brain territory in primary somatosensory cortex (S1) that was “freed up” due to input loss (hereafter deprivation) becomes activated by other body part representations, those neighboring the deprived cortex. If neural resources in the deprived hand area get redistributed to facilitate the representation of other body parts following amputation, how does this process relate to persistent phantom sensation arising from the amputated hand? Subsequent work in humans, mostly with noninvasive neuroimaging and brain stimulation techniques, have expanded on the initial observations of cortical remapping in two important ways. First, research with humans allows us to study the perceptual consequence of remapping, particularly with regards to phantom sensations and pain. Second, by considering the various compensatory strategies amputees adopt in order to account for their disability, including overuse of their intact hand and learning to use an artificial limb, use-dependent plasticity can also be studied in amputees, as well as its relationship to deprivation-triggered plasticity. Both of these topics are of great clinical value, as these could inform clinicians how to treat PLP, and how to facilitate rehabilitation and prosthesis usage in particular. Moreover, research in humans provides new insight into the role of remapping and persistent representation in facilitating (or hindering) the realization of emerging technologies for artificial limb devices, with special emphasis on the role of embodiment. Together, this research affords a more comprehensive outlook at the functional consequences of cortical remapping in amputees’ primary sensorimotor cortex.

Article

Color perception in macaque monkeys and humans depends on the visually evoked activity in three cone photoreceptors and on neuronal post-processing of cone signals. Neuronal post-processing of cone signals occurs in two stages in the pathway from retina to the primary visual cortex. The first stage, in in P (midget) ganglion cells in the retina, is a single-opponent subtractive comparison of the cone signals. The single-opponent computation is then sent to neurons in the Parvocellular layers of the Lateral Geniculate Nucleus (LGN), the main visual nucleus of the thalamus. The second stage of processing of color-related signals is in the primary visual cortex, V1, where multiple comparisons of the single-opponent signals are made. The diversity of neuronal interactions in V1cortex causes the cortical color cells to be subdivided into classes of single-opponent cells and double-opponent cells. Double-opponent cells have visual properties that can be used to explain most of the phenomenology of color perception of surface colors; they respond best to color edges and spatial patterns of color. Single opponent cells, in retina, LGN, and V1, respond to color modulation over their receptive fields and respond best to color modulation over a large area in the visual field.

Article

Kaitlin Farrell, Megan R. Detloff, and John D. Houle

Spinal cord injury has instantaneous, destructive effects on bodily functions, as readily demonstrated by muscle paralysis and non-responsiveness to sensory stimulation. This primary response has underlying features at molecular, cellular, tissue and organ levels which will, in a relatively brief time, initiate a secondary cascade of events that exacerbates the extent of the primary focus of damage. Interestingly, the initial extent of motor and sensory loss often is followed by limited, but significant spontaneous functional recovery. Recovery may be due to intrinsic central pattern generators such as for locomotion, the uncovering of dormant anatomical and physiological pathways such as the crossed phrenic for respiration, or to the sprouting of undamaged axons within the spinal cord to establish new connections around or across the injury site. Together the responses to injury and spontaneous efforts for repair represent plastic changes in the central nervous system (CNS) that may result in meaningful functional outcomes, though aberrant sprouting is a possible negative consequence of neuroplasticity that lends caution to the desire for extensive but uncontrolled sprouting.

Article

Human spinal cord injury (SCI) results in long-lasting disabilities due to the failure of damaged neurons to regenerate. The barriers to axon regeneration in mammalian central nervous system (CNS) are so great, and the anatomy so complex that incremental changes in regeneration brought about by pharmacological or molecular manipulations can be difficult to demonstrate. By contrast, lampreys recover functionally after a complete spinal cord transection (TX), based on regeneration of severed axons, even though lampreys share the basic organization of the mammalian CNS, including many of the same molecular barriers to regeneration. And because the regeneration is incomplete, it can be studied by manipulations designed to either inhibit or enhance it. In the face of reduced descending input, recovery of swimming and other locomotor functions must be accompanied by compensatory remodeling throughout the CNS, as would be required for functional recovery in mammals. For such studies, lampreys have significant advantages. They have several large, identified reticulospinal (RS) neurons, whose regenerative abilities have been individually quantified. Other large neurons and axons are visible in the spinal cord and can be impaled with microelectrodes under direct microscopic vision. The central pattern generator for locomotion is exceptionally well-defined, and is subject to significant neuromodulation. Finally, the lamprey genome has been sequenced, so that molecular homologs of human genes can be identified and cloned. Because of these advantages, the lamprey spinal cord has been a fertile source of information about the biology of axon regeneration in the vertebrate CNS, and has the potential to serve as a test bed for the investigation of novel therapeutic approaches to SCI and other CNS injuries.

Article

The spinal cord is a prime example of how the central nervous system has evolved to execute and retain movements adapted to the environment. This results from the evolution of inborn intrinsic spinal circuits modified continuously by repetitive interactions with the outside world, as well as by developing internal needs or goals. This article emphasizes the underlying neuroplastic spinal mechanisms through observations of normal animal adaptive locomotor behavior in different imposed conditions. It further explores the motor spinal capabilities after various types of lesions to the spinal cord and the potential mechanisms underlying the spinal changes occurring after these lesions, leading to recovery of function. Together, these observations strengthen the idea of the immense potential of the motor rehabilitation approach in humans with spinal cord injury since extrinsic interventions (training, pharmacology, and electrical stimulation) can modulate and optimize remnant motor functions after injury.

Article

Aleksandra Polosukhina and Pierre-Marie Lledo

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Neuroscience. Please check back later for the full article. In adult mammals, the olfactory bulb and the hippocampus are the regions in the brain that undergo continuous neurogenesis (production and recruitment of newborn neurons). While the other regions of the brain still retain a certain degree of plasticity after birth, they no longer can integrate new neurons. In rodents, thousands of adult-born neurons integrate into the bulb each day, and this process has been found to contribute not only to sensory function, but also to olfactory memory. This was a surprising finding, since historically the adult-brain has been viewed as a static organ. Understanding the process of regeneration of mature neurons in the brain has great potential for therapeutic applications. Consequently, this process of adult-neurogenesis has received widespread attention from clinicians and scientists. Neuroblasts bound for the olfactory bulb are produced in the subventricular zone of the lateral ventricle. Once they reach the olfactory bulb, they mostly develop into inhibitory interneurons called granule cells. Just after one month, about half of the adult-born neurons are eliminated, and the other half fully integrate and function in the olfactory bulb. These cells not only process information from the sensory neurons in the bulb, but also receive massive innervation from various regions of the brain, including the olfactory cortex, locus coeruleus, the horizontal limb of diagonal band of Broca, and the dorsal raphe nucleus. The sensory (bottom-up) and cortical (top-down) activity has been found to play a vital role in the adult-born granule cell survival. Though the exact purpose of these newborn neurons has not been identified, some emerging functions include maintenance of olfactory bulb circuitry, modulating sensory information, modulating olfactory learning, and memory.

Article

Rajesh P.N. Rao and Linxing Preston Jiang

Predictive coding is a unifying framework for understanding perception, action, and neocortical organization. In predictive coding, different areas of the neocortex implement a hierarchical generative model of the world that is learned from sensory inputs. Cortical circuits are hypothesized to perform Bayesian inference based on this generative model. Specifically, the Rao–Ballard hierarchical predictive coding model assumes that the top-down feedback connections from higher to lower order cortical areas convey predictions of lower-level activities. The bottom-up, feedforward connections in turn convey the errors between top-down predictions and actual activities. These errors are used to correct current estimates of the state of the world and generate new predictions. Through the objective of minimizing prediction errors, predictive coding provides a functional explanation for a wide range of neural responses and many aspects of brain organization.

Article

All fish have a mechanosensory lateral line system for the detection of hydrodynamic stimuli. It is thus not surprising that the lateral line system is involved in numerous behaviors, including obstacle avoidance, localization of predators and prey, social communication, and orientation in laminar and turbulent flows. The sensory units of the lateral line system are the neuromasts, which occur freestanding on the skin (superficial neuromasts) and within subdermal canals (canal neuromasts). The canals are in contact with the surrounding water through a series of canal pores. Neuromasts consist of a patch of sensory hair cells covered by a gelatinous cupula. Water flow causes cupula motion, which in turn leads to a change in the hair cells’ receptor potentials and a subsequent change in the firing rate of the innervating afferent nerve fibers. These fibers encode velocity, direction, and vorticity of water motions by means of spike trains. They project predominantly to lateral line neurons in the brainstem for further processing of the received hydrodynamic signals. From the brainstem, lateral line information is transferred to the cerebellum and to midbrain and forebrain nuclei, where lateral line information is integrated with information from other sensory modalities to create a three-dimensional image of the hydrodynamic world surrounding the animal. For fish to determine spatial location and identity of a wave source as well as direction and velocity of water movements, the lateral line system must analyze the various types of hydrodynamic stimuli that fish are exposed to in their natural habitat. Natural hydrodynamic stimuli include oscillatory water motions generated by stationary vibratory sources, such as by small crustaceans; complex water motions produced by animate or inanimate moving objects, such as by swimming fish; bulk water flow in rivers and streams; and water flow containing vortices generated at the edges of objects in a water flow. To uncover the mechanisms that underlie the coding of hydrodynamic information by the lateral line system, neurophysiological experiments have been performed at the level of the primary afferent nerve fibers, but also in the central nervous system, predominantly in the brainstem and midbrain, using sinusoidally vibrating spheres, moving objects, vortex rings, bulk water flow, and Kármán vortex streets as wave sources. Unravelling these mechanisms is fundamental to understanding how the fish brain uses hydrodynamic information to adequately guide behavior.

Article

Robert S. Bridges

Prolactin (PRL) is a protein hormone with a molecular weight of approximately 23 KD, although variants in size exist. It binds to receptor dimers on the cytoplasmic surface of its target cells and acts primarily through the activation of the STAT5 pathway, which in turn alters gene activity. Pituitary prolactin, while being the main, but not only, source of PRL, is primarily under inhibitory control by hypothalamic dopaminergic neurons. Release of dopamine (DA) into the hypothalamo-hypophyseal portal system binds on DA D2 receptors on PRL-producing lactotrophs within the anterior pituitary gland. Prolactin’s functions include the regulation of behaviors that include maternal care, anxiety, and feeding as well as lactogenesis, hepatic bile formation, immune function, corpora lutea function, and more generally cell proliferation and differentiation. Dysfunctional conditions related to prolactin’s actions include its role in erectile dysfunction and male infertility, mood disorders such as depression during the postpartum period, possible roles in breast and hepatic cancer, prostate hyperplasia, galactorrhea, obesity, immune function, and diabetes. Future studies will further elucidate both the underlying mechanisms of prolactin action together with prolactin’s involvement in these clinical disorders.

Article

Chuan-Chin Chiao and Roger T. Hanlon

Visual camouflage change is a hallmark of octopus, squid, and cuttlefish and serves as their primary defense against predators. They can change their total body appearance in less than a second due to one principal feature: every aspect of this sensorimotor system is neurally refined for speed. Cephalopods live in visually complex environments such as coral reefs and kelp forests and use their visual perception of backgrounds to rapidly decide which camouflage pattern to deploy. Counterintuitively, cuttlefish have evolved a small number of pattern designs to achieve camouflage: Uniform, Mottle, and Disruptive, each with variation. The expression of these body patterns is based on several fundamental scene features. In cuttlefish, there appear to be several “visual assessment shortcuts” that enable camouflage patterning change in as little as 125 milliseconds. Neural control of the dynamic body patterning of cephalopods appears to be organized hierarchically via a set of lobes within the brain, including the optic lobes, the lateral basal lobes, and the anterior/posterior chromatophore lobes. The motor output of the central nervous system (CNS) in terms of the skin patterns that are produced is under sophisticated neural control of chromatophores, iridophores, and three-dimensional skin papillae. Moreover, arm postures and skin papillae are also regulated visually for additional aspects of concealment. This coloration system, often referred to as rapid neural polyphenism, is unique in the animal kingdom and can be explained and interpreted in the context of sensory and behavioral ecology.

Article

Mindaugas Mitkus, Simon Potier, Graham R. Martin, Olivier Duriez, and Almut Kelber

Diurnal raptors (birds of the orders Accipitriformes and Falconiformes), renowned for their extraordinarily sharp eyesight, have fascinated humans for centuries. The high visual acuity in some raptor species is possible due to their large eyes, both in relative and absolute terms, and a high density of cone photoreceptors. Some large raptors, such as wedge-tailed eagles and the Old World vultures, have visual acuities twice as high as humans and six times as high as ostriches—the animals with the largest terrestrial eyes. The raptor retina has rods, double cones, and four spectral types of single cones. The highest density of single cones occurs in one or two specialized retinal regions: the foveae, where, at least in some species, rods and double cones are absent. The deep central fovea allows for the highest acuity in the lateral visual field that is probably used for detecting prey from a large distance. Pursuit-hunting raptors have a second, shallower, temporal fovea that allows for sharp vision in the frontal field of view. Scavenging carrion eaters do not possess a temporal fovea that may indicate different needs in foraging behavior. Moreover, pursuit-hunting and scavenging raptors also differ in configuration of visual fields, with a more extensive field of view in scavengers. The eyes of diurnal raptors, unlike those of most other birds, are not very sensitive to ultraviolet light, which is strongly absorbed by their cornea and lens. As a result of the low density of rods, and the narrow and densely packed single cones in the central fovea, the visual performance of diurnal raptors drops dramatically as light levels decrease. These and other visual properties underpin prey detection and pursuit and show how these birds’ vision is adapted to make them successful diurnal predators.

Article

William H. Walker II and A. Courtney DeVries

Neuroimmunology is the study of the interaction between the immune system and nervous system during development, homeostasis, and disease states. Descriptions of neuroinflammatory diseases dates back centuries. However, in depth scientific investigation in the field began in the late 19th century and continues into the 21st century. Contrary to prior dogma in the field of neuroimmunology, there is immense reciprocal crosstalk between the brain and the immune system throughout development, homeostasis, and disease states. Proper neuroimmune functioning is necessary for optimal health, as the neuroimmune system regulates vital processes including neuronal signaling, synapse pruning, and clearance of debris and pathogens within the central nervous system. Perturbations in optimal neuroimmune functioning can have detrimental consequences for the host and underlie a myriad of physical, cognitive, and behavioral abnormalities. As such, the field of neuroimmunology is still relatively young and dynamic and represents an area of active research and discovery.

Article

Jimena Perez-Sanchez and Yves De Koninck

One of the most remarkable properties of neural circuits is the ability to restructure their synaptic connections throughout life. This synaptic plasticity allows neurons to structurally reorganize and adapt their function in response to experience. Among the multiple mechanisms that can modulate this property is synaptic inhibition by gamma-Aminobutyric acid (GABA) and/or glycine ionotropic receptors, which allow the flow of chloride and bicarbonate ions through the membrane. Neurons rely upon tight regulation of intracellular chloride for efficient inhibition through these receptors. The maintenance of chloride gradients is important not only to determine the strength of synaptic inhibition but also to determine its nature. Indeed, this inhibition can be hyperpolarizing or depolarizing, or with no outright change in the membrane potential. Despite the fact that membrane depolarization is commonly associated with excitation, depolarizing GABA/glycine can also produce inhibition, thereby highlighting the dual action of these neurotransmitters. Several considerations must be taken into account in order to allow depolarizing GABA/glycine responses to be excitatory. On the other hand, chloride homeostasis is never steady-state and even small changes of chloride across the membrane can impact the strength of inhibition. This dynamic effect has a direct impact on neuronal excitability and makes its regulation by changes in chloride gradients a highly tunable mechanism. Furthermore, increased excitability may also open a window for system refinement changes, such as synaptic plasticity. Indeed, the regulation of chloride homeostasis may underlie periods of enhanced plasticity, such as during early development. Finally, disruption of chloride gradients arises as a hub for pathology, which is evidenced in multiple disorders in the central nervous system.

Article

Daniel J. Bernard, Yining Li, Chirine Toufaily, and Gauthier Schang

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are glycoproteins produced by gonadotrope cells of the anterior pituitary gland. The two hormones act on somatic cells of the gonads in both males and females to regulate fundamental aspects of reproductive physiology, including gametogenesis and steroidogenesis. In males, LH stimulates testosterone production and sperm maturation. FSH also regulates spermatogenesis, though the importance of the hormone in this process differs across species. In females, FSH stimulates ovarian follicle maturation. Follicles are structures composed of oocytes surrounded by two types of somatic cells, granulosa and theca cells. FSH stimulates granulosa cells to proliferate and to increase their production of the aromatase enzyme. LH stimulates theca cells to make androgens, which are converted into estrogens by aromatase in granulosa cells. A surge of LH also stimulates ovulation of mature follicles. Gonadotropin-releasing hormone (GnRH) from the brain is the principal stimulator of gonadotropin synthesis and secretion from the pituitary. The sex steroids (androgens and estrogens) that are produced by the gonads in response to the gonadotropins feedback to the brain and pituitary gland. In the brain, these hormones usually slow the release of GnRH through a process called negative feedback, which in turn leads to decreases in FSH and LH. The steroids also modulate the sensitivity of the pituitary to GnRH in addition to directly regulating expression of the genes that encode the gonadotropin subunits. These effects are gene- and species-specific. In females, estrogens also have positive feedback actions in the brain and pituitary in a reproductive cycle stage-dependent manner. This positive feedback promotes GnRH and LH release, leading to the surge of LH that triggers ovulation. The gonadotropins are dimeric proteins. FSH and LH share a common α-subunit but have hormone-specific subunits, FSHβ and LHβ. The β subunits provide a means for differential regulation and action of the two hormones. In the case of FSH, there is a second gonadal feedback system that specifically regulates the FSHβ subunit. The gonads produce proteins in the transforming growth factor β (TGFβ) family called inhibins, which come in two forms (inhibin A and inhibin B). The ovary produces both inhibins whereas the testes make inhibin B alone. Inhibins selectively suppress FSH synthesis and secretion, without affecting LH. The pituitary produces additional TGFβ proteins called activins, which are structurally related to inhibins. Activins, however, stimulate FSH synthesis by promoting transcription of the FSHβ subunit gene. Inhibins act as competitive receptor antagonists, binding to activin receptors and blocking activin action, and thereby leading to decreases in FSH. Together, GnRH, sex steroids, activins, and inhibins modulate and coordinate gonadotropin production and action to promote proper gonadal function and fertility.

Article

In mammals, reproductive function is closely regulated by energy availability. It is influenced by both extremes of nutrition, too few calories (undernutrition) and an excessive amount of calories (obesity). Atypical decreases or increases in weight can have adverse effects on the reproductive axis. This includes suppression of reproductive function, decreases in ovarian cyclicity, reduction in fertility, anovulation, and dysregulation of spermatogenesis. The balance between energy regulation and reproduction is supervised by a complex system comprised of the brain and peripheral tissues. The brain senses and integrates various systemic and central signals that are indicative of changes in body physiology and energy status. This occurs via numerous factors, including metabolic hormones and nutrients. Adipokines, endocrine factors primarily secreted by white adipose tissue, and adipose tissue related cytokines (adipocytokines) contribute to the regulation of maturity, fertility, and reproduction. Indeed, some adipokines play a fundamental role in reproductive disorders. The brain, predominantly the hypothalamus, is responsible for linking adipose-derived signals to pathways controlling reproductive processes. Gonadotropin-releasing hormone (GnRH) cells in the hypothalamus are fundamental in relaying adipose-derived signals to the pituitary–gonadal axis, which consequently controls reproductive processes. Leptin, adiponectin, apelin, chermin, resistin, and visfatin are adipokines that regulate reproductive events via the brain.

Article

Mathew T. Summers, Malak El Quessny, and Marla B. Feller

Motion is a key feature of the sensory experience of visual animals. The mammalian retina has evolved a number of diverse motion sensors to detect and parse visual motion into behaviorally relevant neural signals. Extensive work has identified retinal outputs encoding directional and nondirectional motion, and the intermediate circuitry underlying this tuning. Detailed circuit mechanism investigation has established retinal direction selectivity in particular as a model system of neural computation.

Article

Jeffrey S. Darling, Kevin Sanchez, Andrew D. Gaudet, and Laura K. Fonken

Microglia, the primary innate immune cells of the brain, are critical for brain maintenance, inflammatory responses, and development in both sexes across the lifespan. Indeed, changes in microglia form and function with age have physiological and behavioral implications. Microglia in the aged brain undergo functional changes that enhance responses to diverse environmental insults. The heightened sensitivity of aged microglia amplifies proinflammatory responses, including increased production of proinflammatory cytokines and chemokines, elevated danger signals, and deficits in debris clearance. Elevated microglia activity and neuroinflammation culminate in neuropathology, including increased risk for neurodegenerative diseases and cognitive decline. Importantly, there are sex differences in several age-related neuroinflammatory pathologies. Microglia coordinate sex-dependent development within distinct brain structures and behaviors and are, in turn, sensitive to sex-specific hormones. This implies that microglia may confer differential disease risk by undergoing sex-specific changes with age. Understanding how aging and sex influence microglial function may lead to targeted therapies for age- and sex-associated diseases and disorders.

Article

Olivia H. Bodart, Ethan P. Glaser, Steven M. MacLean, Meifan A. Chen, and John C. Gensel

Spinal cord injury (SCI) is a life-altering event for which there is no treatment. Depending on injury location and severity, the breadth of the effects can go far past simple mobility. Primary mechanical trauma triggers a variety of secondary cellular events that exacerbate tissue loss as well as facilitate endogenous repair. A large focus of SCI research is on understanding the pathophysiological mechanisms through which these secondary responses contribute to morbidities associated with SCI. Neuroinflammation, a common response to central nervous system (CNS) insult, is central to the secondary injury cascade. In the context of SCI, the inflammatory response plays a contradictory role in recovery; immune cells release both pro- and anti-inflammatory cytokines at the injury site and clear debris while also causing damage to spared tissue. The major innate and adaptive immune cells that respond to SCI are neutrophils, astrocytes, microglia/macrophages, B cells, and T cells. For each cell type, the timing of the cellular response (in both human and rodent models of SCI), the potential role each cell type plays in the pathophysiology of injury, and the therapeutic implications of targeting each cell type for SCI recovery are discussed.

Article

Within the central nervous system, the neuropeptides oxytocin and vasopressin are key regulators of social behavior. While their effects can be nuanced, data suggest that they can influence behavior at multiple levels, including an individual’s personality/temperament, their social interactions in smaller groups (or one-on-one interactions), and their behavior in larger groups. At a mechanistic level, oxytocin and vasopressin help to integrate complex information—including aspects of an animal’s external and internal state—in order to shape behavioral output. Oxytocin and vasopressin help to modulate behaviors that bring animals together (i.e., cooperative behaviors) as well as behaviors that keep animals apart (i.e., competitive behaviors), with the modulatory effects often being species-, sex-, and context-dependent. While there continues to be extensive study of the function of these nonapeptides within individual brain nuclei, over the last two decades behavioral neuroendocrinologists have also made great strides in exploring their roles within larger brain networks that help to regulate social behavior. Looking forward, work on oxytocin and vasopressin will continue to shed light on how the neural regulation of social behaviors are similar, and/or dissimilar, within and between species and sexes, as well as provide insights into the neural chemistry that underlies behavioral differences in neurotypical and neurodivergent individuals.

Article

Kristen Delevich and Linda Wilbrecht

Puberty onset marks the beginning of adolescence and an organism’s transition to adulthood. Across species, adolescence is a dynamic period of maturation for brain and behavior. Pubertal processes, including the increase in gonadal hormone production, or gonadarche, can influence a broad array of neural processes and circuits to ultimately shape adult behavior. Decades of research in rodent models have shown that gonadal hormones at puberty promote adult-typical patterns of behavior across social, affective, and cognitive realms. Importantly, hormonal activation of sex-specific patterns of adult behavior relies on sexual differentiation of the brain around the time of birth, mediated by testicular hormones in males – and lack thereof in females. While it was originally believed that gonadal hormones play a purely activational role at puberty, studies in the early 21st century provide examples where the timing and relative levels of gonadal hormones exert long-lasting, or organizational effects on brain and behavior. In this way, adolescent exposure to gonadal hormones can orchestrate brain and body changes in unison and in some cases tune how the brain responds to gonadal hormones in adulthood. Notably, many of the effects of puberty on behavior may occur indirectly by altering sensitivity to environmental events and an organism’s ability to respond to or learn from experience. These insights from the animal literature provide a framework for understanding how puberty may influence the maturation of complex behaviors and modify risk or resilience to mental health disorders during human adolescence. In sum, puberty interacts with genetics, early life organizational effects of gonadal hormones, experience, and learning processes to shape behavior in adulthood.