Anatomy and physiology of the autonomic nervous system: Implication on the choice of diagnostic/monitoring tools in 2023.

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work.

Morphological peculiarities of the autonomic nervous system in the thoracic region.

BACKGROUND: The aim of the work is to define the morphological peculiarities of the autonomic nervous system (ANS) in the thoracic region. MATERIAL AND METHODS: An anatomical study was performed on 20 cadavers, 17 men and 3 women. We studied cadavers within 24 h of death. We observed the vertebral and prevertebral section of the truncus sympathicus, their morphological peculiarities depending on the type of ANS. To show the intimate relationship of both systems, we also focused on the details of the structure related to the connections of the ANS with the spinal nervous system. RESULTS: In the thoracic region, the segmental arrangement of the truncus sympathicus ganglia prevailed in 16 (80%) cases. Rami communicantes gave anastomoses to spinal nerves. Small ganglia were observed on the rami communicantes to the spinal nerves. In the case of the concentrated type, in 4 cases (20%), we observed a reduction in the number of ganglia, as well as the absence of small ganglia on the connecting branches. Connections between n. vagus and sympathetic branches were poorly developed. We observed right-left asymmetry and differences in the formation of ganglia and anastomoses in the truncus sympathicus in the vertebral and prevertebral section. Variations of distance of n. splanchnicus major were observed in 16 cases (80%). CONCLUSION: This study allowed us to identify and describe the morphological peculiarities of the thoracic ANS. The variations were numerous; their preoperative diagnosis is difficult to impossible. The knowledge gained can be helpful in clarifying clinical signs and symptoms.

Morphotopographic characteristics of the extrinsic innervation of the heart in guinea pigs (Cavia porcellus).

BACKGROUND: No reports have been made on the entire extrinsic innervation of the heart in small laboratory animals. Therefore, this study examined the detailed morphotopographic features of the extrinsic cardiac autonomic nervous system (ECANS) with its adjacent structures (1) to record the general morpho-topography and variations of the ECANS in guinea pigs, (2) to compare it with previous reports on common laboratory rodents (rats, mice, and Syrian hamsters), rabbits, domesticated animals (cats, dogs, sheep, goats, oxen, pigs, and horses), primates, and humans, and (3) to infer the macroscopic evolutionary changes they presented. METHODS: The sympathetic ganglia, vagi, and emitting cardiac nerves/branches in the cervical and thoracic regions were dissected in 24 sides of 12 formalin-fixed, arterially injected adult male and female guinea pigs under a stereomicroscope. RESULTS: The ECANS in guinea pigs presented following general morphologic characteristics: (1) constant existence of the cranial cervical ganglion (CG) and placing caudal to the cranial base over the ventrolateral aspect of the longus capitis muscle, dorsomedial to the common carotid artery and communicating to the first two cervical spinal nerves, (2) the lack of the vago-sympathetic trunk, (3) the existence of the middle cervical ganglion (MG) and lying on the lateral aspect of the longus colli muscle (LC) at the level of the seventh cervical vertebra, (4) constant existence of the cervicothoracic ganglion (CT) composing generally from the caudal cervical ganglion and 1-3 thoracic ganglia and placing ventral to the first and second intercostal spaces over the lateral aspect of the LC and communicating to the eight cervical and first three thoracic spinal nerves in addition to the vertebral nerve, (5) constant existence of the limbs of the ansa subclavia (AS) joining the CT to MG, (6) the existence of individual thoracic ganglia from the 4th to the 12th and joining by single interganglionic branches (IGBs), and communicating to corresponding thoracic nerve, (7) the intimate relation between the caudal part of the thoracic sympathetic chain and the quadratus lumborum muscle, (8) the main cardiac nerves (CNs) emerging from the CT, (9) the lack of CNs springing generally from the CG, ST, AS, MG, or individual thoracic ganglia or their IGBs, and (10) the existence of the cardiac branches (CBs) emerging from the vagi and recurrent laryngeal nerves. The ECANS morphology in guinea pigs also shows sex and laterality differences. CONCLUSIONS: The general anatomical arrangement of the sympathetic components of the ECANS in guinea pigs extremely displaced features common to rats and Syrian hamsters regardless of the existence of MG and the close relation between the thoracic sympathetic chain and the quadratus lumborum muscle. However, the position and organization of the CT, along with its rami communicantes to spinal nerves in guinea pigs quite resembled those seen in rats. The general macroscopic arrangement of the sympathetic components of the ECANS in guinea pigs resembled that seen in rabbits regardless of the organization and location of the CT. The general morphology of the sympathetic components of the ECANS demonstrated markedly morphological variations and similarities among common laboratory rodents, rabbits, domesticated animals (DNs), primates, and humans. The main variations consisted of the position of the CG and its rami communicantes with the spinal nerves, the relation between the vagi and sympathetic trunks in the neck, the existence of the MG, the location and arrangement of the CT, the origins and incidences of the cardiac nerves, and the main sympathetic contributors. The general macroscopic architecture of the parasympathetic components of the ECANS in guinea pigs quite resembled that seen in domesticated animals, primates, and humans. Evolutionary comparative morphologic characteristics of the ECANS are discussed in detail and evolutionary differences and similarities of the ECANS have been found from common laboratory rodents, rabbits, domesticated animals, and primates to humans.

El término glía, una tradición conceptual errada: propuesta de cambio por sinneuronas / The term glia, a wrong conceptual tradition: proposal for change for synneurons

RESUMEN: Desde su descubrimiento, las células no neuronales del sistema nervioso recibieron el nombre de glia, palabra de origen griego que significa unión o pegamento, porque se creía que su función era formar una especie de masilla en la que se encuentran inmersas las neuronas. Desde entonces, mediante nuevas técnicas de tinción, se descubrieron otros tipos celulares que fueron catalogados también como glía, que hasta la fecha siguen siendo consideradas como las células de unión o pegamento del tejido nervioso. El objetivo de este artículo es cuestionar el uso inadecuado del término glía y proponer un nuevo término para designar a las células no neuronales. A pesar del enorme conocimiento que actualmente se tiene de estas células y de la gran variedad de funciones que realizan para mantener el correcto funcionamiento de las neuronas y los circuitos nerviosos, aún se les conserva el nombre de glía, un término errado que desdibuja el verdadero papel que cumplen y su importancia para el sistema nervioso. Por lo anterior, se propone el término "sinneuronas", del prefijo griego syn que significa con o junto con, lo que daría a entender que son células que presentan cercanía estructural y funcional con las neuronas.

SUMMARY: Since their discovery, the non-neuronal cells of the nervous system have been called glia, a word of Greek origin that means union or glue, because it was believed that their function was to form a kind of putty, in which neurons are immersed. Thereafter, new cell types discovered by new staining techniques, were also classified as glia, which to this day are still considered as binding cells or glue of nerve tissue. The objective of this paper is to question the inappropriate use of the term glia and to propose a new term to designate non-neuronal cells. Despite the enormous knowledge that is currently available of these cells and the great variety of functions they perform to maintain the proper functioning of neurons and nerve circuits, they still retain the name of glia, an inappropriate name that blurs the true role they play. Therefore, the term "synneuronas" is proposed, from the Greek prefix syn which means with or together with, what would suggest that they are cells that present structural and functional proximity with to neurons.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

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Anatomical evidence for the efferent pathway from the hypothalamus to autonomic innervation in the anterior chamber structures of eyes.

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.

Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation.

BACKGROUND: Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. OBJECTIVE: To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. RESULTS: In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. CONCLUSION: Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.

Neurovascular and lymphatic vessels distribution in uterine ligaments based on a 3D reconstruction of histological study: to determine the optimal plane for nerve-sparing radical hysterectomy.

OBJECTIVE: To present the distribution of neurovascular and lymphatic vessels in uterine ligaments using 3D models based on the pathological staining of serial 2D sections of postoperative specimens. METHODS: Serial transverse sections of fresh uterine ligaments from a patient with stage IB1 cervical squamous cell carcinoma were studied using the computer-assisted anatomic dissection (CAAD) technique. The sections were stained with hematoxylin and eosin, Weigert elastic fibers, D2-40 and immunostainings (sheep anti-tyrosine hydroxylase and rabbit anti-vasoactive intestinal peptide). The sections were then digitalized, registered and reconstructed three-dimensionally. Then, the 3D models were analyzed and measured. RESULTS: The 3D models of the neurovascular and lymphatic vessels in uterine ligaments were created, depicting their precise location and distribution. The vessels were primarily located in the upper part of the ligaments model, while the pelvic autonomic nerves were primarily in the lower part; the lymphatic vessels were scattered in the uterine ligaments, without obvious regularity. CONCLUSION: CAAD is an effective anatomical method to study the precise distribution of neurovascular and lymphatic vessels in uterine ligaments. It can present detailed anatomical information about female pelvic autonomic innervation and the spatial relationship between nerves and vessels and may provide a better understanding of nerve-sparing radical hysterectomy.

Autonomic nervous system of the pelvis - general overview.

Autonomic nervous system of the pelvis is still poorly understood. Every year more and more pelvic procedures are carried out on patients suffering from different pelvic disorders what leads to numerous pelvic dysfunctions. Authors tried to review, starting from historical and clinical background, the most important reports on anatomy of the pelvic autonomic plexuses. We also pay attention to complete lack of knowledge of students of medicine on the autonomic nervous structures in the area studied. We present anatomical description of the pelvic plexuses including their visceral branches and anatomy of surrounding pelvic tissues which still remains unclear. More and more attention is paid to the topography of the plexuses specially because of new pain releasing techniques - neurolysies.

The inferior turbinate: An autonomic organ.

The inferior turbinate has well-recognized respiratory and immune functions to provide the airway with appropriate warmth, humidification, and filtration of the inspired air while sampling the environment for pathogens. Normal functioning of the inferior turbinate relies on an intact autonomic system to maintain homeostasis within the nasal cavity. The autonomic nervous system innervates the submucosal glands and the vasculature within the inferior turbinate, resulting in control of major turbinate functions: nasal secretions, nasal patency, warmth, and humidification. This review will summarize the autonomic innervations of the turbinates, both the normal and abnormal autonomic processes that contribute to the turbinate functions, and the clinical considerations regarding optimal functioning of the turbinate autonomic system.

Heart rate variability associated with grey matter volumes in striatal and limbic structures of the central autonomic network.

Previous neuroimaging studies have highlighted the functional neural correlates of cardiac vagal activity, providing convergent evidence that the cardiac vagal function is controlled by a number of brain regions in the central autonomic network (CAN). However, it remains largely unknown whether the underlying anatomical basis of those identified regions are associated with individual difference in vagal function. To address the above issue, this study used a large sample of healthy subjects (n = 185) and voxel-based morphometry (VBM) analysis to verify brain morphometry associated with vagal control and the associations varied as a function of gender and age. Our results showed that high frequency component of heart rate variability (HF-HRV) was negatively correlated with grey matter volumes in the right putamen, caudate, amygdala, insula, superior temporal gyrus, temporal pole, and parahippocampal gyrus, demonstrating brain morphological variation in the right-sided striatal and limbic structures of the CAN associated with individual difference in cardiac vagal function. Additionally, gender and age effects on the relationship between cardiac vagal control and brain morphometry were not significant in the current dataset. These findings underscore the importance of striatal and limbic structures in parasympathetic control, and shed light on the underlying anatomical substrates of cardiac vagal activity.

Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature.

Several concepts developed in the nineteenth century have formed the basis of much of our neuroanatomical teaching today. Not all of these were based on solid evidence nor have withstood the test of time. Recent evidence on the evolution and development of the autonomic nervous system, combined with molecular insights into the development and diversification of motor neurons, challenges some of the ideas held for over 100 years about the organization of autonomic motor outflow. This review provides an overview of the original ideas and quality of supporting data and contrasts this with a more accurate and in depth insight provided by studies using modern techniques. Several lines of data demonstrate that branchial motor neurons are a distinct motor neuron population within the vertebrate brainstem, from which parasympathetic visceral motor neurons of the brainstem evolved. The lack of an autonomic nervous system in jawless vertebrates implies that spinal visceral motor neurons evolved out of spinal somatic motor neurons. Consistent with the evolutionary origin of brainstem parasympathetic motor neurons out of branchial motor neurons and spinal sympathetic motor neurons out of spinal motor neurons is the recent revision of the organization of the autonomic nervous system into a cranial parasympathetic and a spinal sympathetic division (e.g., there is no sacral parasympathetic division). We propose a new nomenclature that takes all of these new insights into account and avoids the conceptual misunderstandings and incorrect interpretation of limited and technically inferior data inherent in the old nomenclature.

An introduction into autonomic nervous function.

The results of many medical measurements are directly or indirectly influenced by the autonomic nervous system (ANS). For example pupil size or heart rate may demonstrate striking moment-to-moment variability. This review intends to elucidate the physiology behind this seemingly unpredictable system. The review is split up into: 1. The peripheral ANS, parallel innervation by the sympathetic and parasympathetic branches, their transmitters and co-transmitters. It treats questions like the supposed sympatho/vagal balance, organization in plexuses and the 'little brains' that are active like in the enteric system or around the heart. Part 2 treats ANS-function in some (example-) organs in more detail: the eye, the heart, blood vessels, lungs, respiration and cardiorespiratory coupling. Part 3 poses the question of who is directing what? Is the ANS a strictly top-down directed system or is its organization bottom-up? Finally, it is concluded that the 'noisy numbers' in medical measurements, caused by ANS variability, are part and parcel of how the system works. This topical review is a one-man's undertaking and may possibly give a biased view. The author has explicitly indicated in the text where his views are not (yet) supported by facts, hoping to provoke discussion and instigate new research.

Autonomic nervous system in acute kidney injury.

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented.

Combined maceration procedure permits advanced microsurgical dissection of Thiel-embalmed specimens.

INTRODUCTION: Due to the realistic colour, texture conservation and preservation of biomechanical properties, Thiel-embalming is becoming the main embalming procedure for clinical courses and research based on human cadaver material. The aim of this study is to establish a new procedure that allows advanced microdissection of small vessels and intraorganic nerves in Thiel-embalmed material. MATERIAL AND METHODS/RESULTS: After a classical gross anatomical dissection, human hemipelves underwent repetitive application of 3 consecutive steps: (i) maceration with alloy of nitric acid and MiliQ water 1:10 for 24-48h. (ii) Immersion: the hemipelves were rinsed under tap water for 20-30min. and placed in a water bath for 1h. The nerves become more prominent due to the swelling and increased water content. (iii) microdissection under surgical microscope. To facilitate the organ visualization perfusion with polyurethane (Pu4ii, VasQtec®, Switzerland) in red/blue for arteries/veins respectively has been performed. CONCLUSION: By using the proposed procedure, we performed satisfactory microdissection on Thiel-embalmed samples. The combination with polyurethane vascular casting permits visualization of small arterioles and venules in a range of 20-25µm. The method is very suitable for demonstration of somatic and vegetative nerves. Branches of the sacral plexuses and autonomic nerves from the superior and inferior hypogastric plexus have been tracked up to the smallest intraorganic branches in a range of 12.5-15µm. In conclusion, the established combined procedure offers a new possibility for advanced microdissection, which will allow acquisition of clinically relevant information about organ specific micro- vascularization and innervation.

A fully automatic nerve segmentation and morphometric parameter quantification system for early diagnosis of diabetic neuropathy in corneal images.

Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the nerve structures can assist the early diagnosis of this disease. This paper proposes a robust, fast and fully automatic nerve segmentation and morphometric parameter quantification system for corneal confocal microscope images. The segmentation part consists of three main steps. First, a preprocessing step is applied to enhance the visibility of the nerves and remove noise using anisotropic diffusion filtering, specifically a Coherence filter followed by Gaussian filtering. Second, morphological operations are applied to remove unwanted objects in the input image such as epithelial cells and small nerve segments. Finally, an edge detection step is applied to detect all the nerves in the input image. In this step, an efficient algorithm for connecting discontinuous nerves is proposed. In the morphometric parameters quantification part, a number of features are extracted, including thickness, tortuosity and length of nerve, which may be used for the early diagnosis of diabetic polyneuropathy and when planning Laser-Assisted in situ Keratomileusis (LASIK) or Photorefractive keratectomy (PRK). The performance of the proposed segmentation system is evaluated against manually traced ground-truth images based on a database consisting of 498 corneal sub-basal nerve images (238 are normal and 260 are abnormal). In addition, the robustness and efficiency of the proposed system in extracting morphometric features with clinical utility was evaluated in 919 images taken from healthy subjects and diabetic patients with and without neuropathy. We demonstrate rapid (13 seconds/image), robust and effective automated corneal nerve quantification. The proposed system will be deployed as a useful clinical tool to support the expertise of ophthalmologists and save the clinician time in a busy clinical setting.

Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation.

OBJECTIVE: Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. APPROACH: This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. MAIN RESULTS: We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016.

Commentary on: Saper CB, Loewy AD, Swanson LW, Cowan WM. (1976) Direct hypothalamo-autonomic connections. Brain Research 117:305-312.

The 1970s saw the introduction of new technologies for tracing axons both anterogradely and retrogradely. These methods allowed us to visualize fine, unmyelinated pathways for the first time, such as the hypothalamic pathways that control the autonomic nervous system. As a result, we were able to identify the paraventricular nucleus and lateral hypothalamus as the key sites that provide direct inputs to the autonomic preganglionic neurons in the medulla and spinal cord. These findings revolutionized our understanding of hypothalamic control of the autonomic nervous system.