F7 – ANS Autonomic Nervous System PDF

F7 – ANS The autonomic nervous system is the portion of the nervous system that controls most visceral functions of the body. This system helps to control arterial pressure, gastrointestinal motility, gastrointestinal secretion, urinary bladder emptying, sweating, body temperature, and many other a...

F7 – ANS The autonomic nervous system is the portion of the nervous system that controls most visceral functions of the body. This system helps to control arterial pressure, gastrointestinal motility, gastrointestinal secretion, urinary bladder emptying, sweating, body temperature, and many other activities. Some of these activities are controlled almost entirely and some only partially by the autonomic nervous system. 1.​ ≠ with Somatic nervous system Absence of Somatotopic Organisation at the level of the spinal cord: The proximal and distal muscles are organised in a specific mediolateral way and this type of organisation in the visceral motor system is not clearly detectable. The lower motor neurons in the visceral motor system are located outside the spinal cord: On the other hand, the motor neurons in the CNS are located in the Lamina IX and directly in contact with some specific muscle fibres. The contact between the visceral motor axons and tissue is much less differentiated with respect to the neuromuscular junction: The activity of the nerves associated with the ANS are diffused and their function on the specific tissues is nonspecific and they work on the overall tissue rather than some specific motor units as in the Somatic NS. Terminals of visceral motor neurons release a variety of neurotransmitters that interact with different types of receptors: At the same time in the somatic NS, there are mainly acetylcholine and cholinergic receptors. Central autonomic networks include different structures with respect to the somatic NS that control voluntary movement. It is known that the primary motor cortex and motor areas are the main areas that directly control the skeletal muscles and voluntary movements. However this kind of organisation is different in the ANS. This is due to the reason that the autonomic NS is phylogenetically older than the CNS. The presence of myelination is important because it affects the velocity of the input. This is another difference between the control of skeletal muscle axons and smooth & cardiac muscle axons. 2.​ Historical aspects W.H Gaskell discovered in 1866 that all organs are innervated by two different sets of nerves and this was one of the first discoveries by means of electrical stimulation on the animal models such as cats, monkeys and mouse. It is found that there is kind of an opposite innervation of the organs. One from these two different sets of nerves is increasing the activity of the specific organ and the other is decreasing the activity of the specific organ. The term “Autonomic Nervous system” is associated with John Langley who has found the presence and function of autonomic ganglia. From a functional point of view Claude Bernard has given his attention on the association of our organs and stability of the internal environment. Finally, Walter Cannon associated the function of ANS on the concept of homeostasis. He first introduced the concept of homeostasis, the mechanism to maintain the equilibrium of the internal environment and he investigated the role of ANS in relation to homeostatic mechanism. 3.​ ≠ between the central autonomic system and the peripheral autonomic system The central autonomic nervous system involves the nuclei located from the level of the spinal cord up to the cortex via the brainstem. At the level of the brainstem, there are a lot of nuclei that are related to the control of visceral motor activity. The peripheral nervous system includes -​ visceral sensory neurons, -​ preganglionic efferent fibers -​ postganglionic efferent fibers. The functional division is done by John Langley and due to the cortical stimulation, it is found that ANS basically has three different branches that have different functional roles and different anatomical organizations. The subdivisions of the ANS are like following: ​ Sympathetic Division ​ Parasympathetic Division ​ Enteric Division (which is specifically associated with the gut) General organisation Regarding the general organization of sympathetic and parasympathetic divisions at the level of the brainstem and spinal cord, there are specific neurons located in the specific sectors of the spinal cord and they communicate to an intermediate structure that is located outside the spinal cord which is called a ganglion. Sympathetic and parasympathetic ganglia are located in different positions and have different peculiarities. The first type of neurons before the ganglion is referred to as the preganglionic neurons and the second type of neurons which is after the ganglion is called the postganglionic neurons. They communicate via synapses which occur at the level of ganglia. This type of organization is quite different from the somatic motor system because there is no intermediate structure such as the ganglion in the somatic motor system. The preganglionic neurons are sort of interneurons, while the postganglionic neurons are the motor neurons of the ANS that actually triggers the activity of specific effector organs. Another peculiarity is that there are many more autonomic motor neurons present than somatic motor neurons. Only in the ganglia at the cervical level, there are about 900 000 autonomic neurons. While overall our somatic motor neurons are quite less about 120 000. The reason for this is quite unknown but it could be the huge complexity of the control of the different muscles of the viscera. The preganglionic neurons control the activity of the postganglionic neurons that are located in specific ganglia. The communication between them is occurring via a specific type of neurotransmitter, which is Acetylcholine. The activity of postganglionic neurons is basically associated with the specific nicotinic post-ganglionic receptor for acetylcholine. Its role is to produce fast excitatory postsynaptic potential in the smooth muscle. 4.​ Distinguishing features between subdivisions of the ANS The ≠ between parasympathetic and sympathetic systems are: -​ Segmental organisation of the preganglionic neurons in the spinal cord and the brainstem  o​ Sympathetic division preganglionic neurons are located in the thoracic and lumbar segments of the spinal cord o​ Parasympathetic division preganglionic neurons are located in the first cranial segments and the sacral segments of the spinal cord -​ Peripheral location of their ganglia (intermediate structures) -​ Types and location of the end-organs they innervate -​ Effects they produce on the end-organs -​ NT employed by their post-ganglionic neurons I.​ Parasympathetic system As Walter Cannon has already suggested in his studies the huge activation of the parasympathetic system is associated with a sort of state defined as the “rest and digest” system. More recently Robert M. Spolsky investigated the association of the autonomic nervous activity in the stress situation. 1.​ Organisation It has cranial and spinal divisions: -​ cranial division, the main nerve of the preganglionic neurons are associated with: o​ Oculomotor Nerve (III o​ Facial Nerve (VII) o​ Glossopharyngeal Nerve (IX) o​ Vagus Nerve (X) These are specific nerves located in the brain stem and they are associated with the specific nuclei which will be explained in the following. -​ sacral division, the preganglionic neurons are located within the S2-S4 sacral segments. Their cell bodies are located in an intermediate region of the spinal cord and they project via the ventral root (similar to the alpha motor neurons of the skeletal muscle in the somatic NS). From the  ventral root, they project directly to the ganglia of the parasympathetic system. 2.​ Cranial subdivision The oculomotor nerve (CN III) has its soma in the Edinger-Westphal nucleus, located in the midbrain. EDW innervates the ciliary ganglion via the oculomotor nerve and mediates construction of the pupil in response to increased light. The facial nerve (CN VII) and the glossopharyngeal nerves (CN IX) have their soma located in the superior and inferior salivatory nucleus. They are located in the pons and medulla. Both innervate the salivary glands and tear glands, mediating salivary secretion and the production of tear by synapsing with two different ganglia called the pterygopalatine ganglion and the other one is (through the lingual nerve) the submandibular ganglion. The inferior salivatory nucleus synapses with the otic ganglion, a parasympathetic ganglion controlling the activity of the parotid gland and the large salivary gland. Vagus nerve (CN X) is associated with the ambiguous nucleus, sending projections for cardioinhibitory activity, and the dorsal motor nucleus of the vagus nerve. The dorsal motor nucleus of the vagus nerve is formed of a ventral segment and a dorsal segment. The ventral segment is associated with glandular secretion at the level of the enteric nervous system. The dorsal segment is associated with the nucleus ambiguous for the control of the heart and lungs. 3.​ Sacral subdivision Mainly the preganglionic neurons are located in the lateral grey matter of the sacral spinal cord (as indicated in the image below) and via the ventral root of the spinal cord send their projections to specific parasympathetic ganglia that are mainly located close to the viscera. The nerve that connects the lateral grey matter of the spinal cord with the parasympathetic postganglionic neuron at the sacral level is called the pelvic splanchnic nerve. All the information is sent through these preganglionic nerves to the viscera and it controls -​ the lower part of the colon, -​ the rectum, -​ the bladder, -​ the reproductive organs RECAP  II.​ Sympathetic nervous system This system is called the “fight or flight system”. All the organs are in a specific activity which is the completely opposite function of the parasympathetic organization. The balance between the sympathetic and parasympathetic systems is crucial for our homeostasis. 1.​ Organisation They are located from T1 to L3 (thoracolumbar part of the spinal cord). -​ The thoracic part (the most upper part) is associated with the organs of the head and thorax. -​ The lower preganglionic neurons are responsible for the control of the abdominal and pelvic organs. The preganglionic neurons of the sympathetic division are located in two specific sectors which are the central autonomic area and the intermediolateral cell column. These are locations that are similar to the preganglionic parasympathetic neurons. The main differences of the sympathetic organization is that -​ their preganglionic axons are very short with respect to the parasympathetic preganglionic neurons. -​ the ganglions of the sympathetic system are not close to the effector organs as in the parasympathetic organization. But in this case, the sympathetic ganglia are closer to the extension of the spinal cord. 2.​ ≠ types of sympathetic ganglia The communication between the preganglionic neurons and the effector organs can be established via 3 type of sympathetic ganglia (most of them are close to the spinal cord): ​ Paravertebral ganglion in the sympathetic chain (far from the effector organs) ​ Prevertebral Ganglion is the ganglion that is outside the paravertebral sympathetic chain ​ Directly (Adrenal Medulla) which is a special connection of the preganglionic neurons to the Chromaffin cells in the adrenal medulla involved in the production of noradrenaline 3.​ Paravertebral organisation The paravertebral sympathetic chain extends bilaterally (on the right and left) from the first cervical segment to the last sacral segment. It is lateral to the vertebral column and contains one ganglion per segment innervating smooth muscles, cardiac muscles, and glands. There are two exceptions which are superior cervical ganglion and stellate ganglion. They are not located directly at the paravertebral sympathetic chain but located mainly in the prevertebral ganglion. -​ The role of the superior cervical ganglion is the sympathetic innervation of the head and cerebral vasculature. -​ The role of the stellate ganglion is associated with the innervation of the heart and lungs. All the other ganglia innervate the viscera of the gut or viscera below the chest. 4.​ Prevertebral organisation The prevertebral organization is organized around 3 different ganglia which are: ​ Celiac Ganglion ​ Superior Mesenteric Ganglion ​ Inferior Mesenteric Ganglion The preganglionic neurons of the sympathetic chain project to the prevertebral ganglia located in the midline close to the arteries. The postganglionic axons arising from the prevertebral ganglia provide sympathetic innervation to the, lungs, gut, kidneys, pancreas, liver, bladder, and reproductive organs. The cardiac plexus is located in the prevertebral ganglion but is regulated by paravertebral synapses. 5.​ Adrenal Medulla The preganglionic fibers in the splanchnic nerves send their projections directly to the adrenal medulla. The adrenal medulla is considered as a sort of modified sympathetic ganglion for endocrine functions: the release of catecholamines into the circulation to enhance a widespread sympathetic response to stress. This is another picture related to the paravertebral and prevertebral preganglionic organization (see the image below). As you can see there are preganglionic neurons that are located in the lateral part of the spinal cord that sends visceral efferent fibers via the peripheral nerve. This peripheral nerve goes through the white communicating ramus. The reason for it to be called “white” is that it contains myelinated fibers. The output (the postganglionic fibers) through paravertebral ganglia are less myelinated that's why they are referred to as the gray communicating ramus. The presence of myelination is important because it affects the velocity of the input. This is another difference between the control of skeletal muscle axons and smooth & cardiac muscle axons. The fibers projecting to the prevertebral ganglia don't synapse at the paravertebral ganglia in the sympathetic chain. They go directly from the prevertebral ganglia to the viscera (as depicted in the image below). The fibers running from the chain can go up and down and are able to modulate the activity of other preganglionic neurons and the postganglionic neurons. With this kind of organization, the sympathetic nervous system can have a very diffuse role in modulating the postganglionic activity. RECAP  6.​ ≠ between sympathetic and parasympathetic inneration Parasympathetic ganglia generally innervate single end-organs and lie near to or within the end-organs that they regulate. So the axons of the preganglionic parasympathetic neurons are longer than the axons of the sympathetic preganglionic neurons. Sympathetic ganglia tend to have extensive dendritic arbors and are innervated by a large number of preganglionic fibers which doesn't happen in the parasympathetic system because the parasympathetic ganglion is innervated only by one or a few preganglionic axons. The innervation of the parasympathetic system does not influence skin or skeletal muscle except in the head, where it regulates vascular beds in the jaw, lip, and tongue. Although most of the organs receive innervation from both systems some organs only receive sympathetic innervation: ​ sweat glands, ​ the adrenal medulla ​ piloerector muscles of the skin ​ most arterial blood vessels III.​ Enteric nervous system An enormous number of neurons are specifically associated with the gastrointestinal tract to control its many functions. As already noted, the activity of the gut is modulated by both the sympathetic and parasympathetic divisions of the visceral motor system. However, the gut also has an extensive system of nerve cells in its wall (as do its accessory organs such as the pancreas and gallbladder) that do not fit neatly into the sympathetic or parasympathetic divisions of the visceral motor system. To a surprising degree, these neurons and the complex enteric networks in which they are found operate more or less independently according to their own reflex rules. As a result, many gut functions continue perfectly well without sympathetic or parasympathetic supervision (peristalsis, for example, occurs in isolated gut segments in vitro). Thus, most investigators prefer to classify the enteric nervous system as a unique, autonomic component of the visceral motor system. The neurons in the gut wall include -​ local and centrally projecting sensory neurons that monitor mechanical and chemical conditions in the gut, -​ local circuit neurons that integrate this information -​ motor neurons that influence the activity of the smooth muscles in the wall of the gut and glandular secretions (e.g., of digestive enzymes, mucus, stomach acid, and bile). This complex arrangement of nerve cells intrinsic to the gut is organized into  (1)​ the myenteric (or Auerbach’s) plexus, which is specifically concerned with regulating the musculature of the gut (2)​ the submucous (or Meissner’s) plexus, which is located, as the name implies, just beneath the mucus membranes of the gut and is concerned with chemical monitoring and glandular secretion Preganglionic parasympathetic neurons that influence the gut are primarily in the dorsal motor nucleus of the vagus nerve in the brainstem and the intermediate gray zone in the sacral spinal cord segments. The preganglionic sympathetic innervation that modulates the action of the gut plexuses derives from the thoraco-lumbar cord, primarily by way of the celiac, superior mesenteric ganglion, and inferior mesenteric ganglia. 1.​ Sensory components of the visceral motor system Our visceral system requires specific sensory feedbacks to regulate its activity. Receptors present are visceral receptors and are -​ mechanical receptors -​ chemical receptors Generally speaking, afferent activity arising from the vis-cera serves two important functions. ​ provides feedback to local reflexes that modulate moment-to-moment visceral motor activity within individual organs., ​ informs higher integrative centers of more complex patterns of stimulation that may signal potentially threatening conditions or require the coordination of more widespread visceral motor, somatic motor, neuroendocrine, and behavioral activities 2.​ Nucleus of the solitary tract The nucleus of the solitary tract, located in the medulla oblongata is the central structure in the brain that receives visceral sensory information. Its caudal part contributes to a reflexive control of visceral motor function and relay visceral sensory information to other brainstem structures. It recieves inputs from: -​ Spinal visceral sensory neurons in the dorsal roots -​ Sensory neurons that travel in the glossopharyngeal and vagus cranial nerves a.​ Spinal visceral sensory neurons Spinal visceral sensory neurons in the dorsal roots are ​ Nerve endings sensitive to pressure, stretch; ​ Nerve endings that innervate specialized chemosensitive cells; ​ Nociceptive endings signaling damaging strecth, ischemia or riiritating chemicals. This information is sent to different locations of spinal cord, -​ in intermediate zone where are located the preganglionic neurons which are implicated in visceral reflexes, -​ projections at the level of the dorsal horn are sent via the anterolateral system and send this information mainly to o​ the nucleus of the solitary tract o​ specific visceral motor centres in reticular formation. -​ Projections through the DCML (dorsal column), this is involved information regarding pain and visceral state of our organs. The NST receives afferent sensory fibres from glossopharyngeal and vagus nerves. The visceral sensory information reaches the caudal part of the nucleus, while the rostral part is associated with the gustatory division. When afferents reach this structures the rostral portion send gustatory inputs to the thalamus, The caudal portion send its inputs to a variety of structure which include -​ specific viscero-motor neurons in brainstem and reticular formation, -​ specific nuclei associated to the limbic system like the o​ amygdala o​ hypothalamus o​ parabrachial nucleus (associated to homeostasis).  3.​ Outputs and modulation of activity The outputs from NTS are going to -​ autonomic centres of reticular formation, -​ hypothalamus -​ amygdala. -​ insula cortex. Overall, this network is called central autonomic network and it is involved in integration of visceral sensory info with inputs of other sensory modalities and higher cognitive centres (processing semantic and emotional experiences). Hypothalamus is considered a key component: it is the major centre coordinating the expression of visceromotor activity and sends specific inputs to -​ motor nucleus of reticular formation, -​ cranial nerves hosting parasympathetic preganglionic neurons -​ mediolateral regions of spinal cord where sympathetic preganglionic and also parasympathetic preganglionic neurons are hosted. It is able to modulate the two branches of the autonomic nervous systems. Reticular formation: the activation of reticular systems involves the awake state (as seen in sleep lecture) and this increases several parameters of heart, respiration and other reflexes. It is considered a sort of premotor cicuit able to coordinate the actvity of preganglionic visceral motor neurons controlling cardiac reflexes, bladder reflexes and reflexes related to sexual functions Within the system of the NST regarding the afferent pathway and the hypothalamus regarding the efferent it is found a sort of T structure: the NST receives afferent information and the hypothalamus receives information directly and indirectly via the NST. The hypothalamus then coordinates the output to the specific preganglionic neurons that control the sympathetic and parasympathetic systems. 4.​ Neurotransmission We have some differences in neurotransmission: The preganglionic transmission of information (preganglionic to postganglionic) is mainly mediated by acetylcholine (Ach). The post ganglionic transmission of the input is mediated by -​ norepinephrine (sympathetic system) -​ acetylcholine (parasympathetic): the receptor at the post-synaptic membrane is a muscarinic receptor (associated with slow EPSP) while the one at the preganglionic transmission is nicotinic ( associated with fast EPSP), a ≠ receptor compared to the preganglionic transmission is present. The specific effects of ACh and NE are determined by the type of receptor expressed in the target tissue and the downstream signaling pathways to which these receptors are linked. Peripheral sympathetic targets generally have two subclasses of noradrenergic receptors in their cell membranes, referred to as α and β receptors. They are subdivided into α1, α2, β1 and β2 receptors. Like muscarinic ACh receptors, both α and β receptors and their subtypes belong to the 7-trans- membrane G-protein-coupled class of cell surface receptors. The different distribution of these receptors in sympathetic targets allows for a variety of postsynaptic effects mediated by norepinephrine released from postganglionic sympathetic nerve endings. The effects of acetylcholine released by parasympathetic ganglion cells onto smooth muscles, cardiac muscle, and glandular cells also vary according to the subtypes of muscarinic cholinergic receptors found in the peripheral target. The two major subtypes are known as M1 and M2 receptors, -​ M1 receptors being found primarily in the gut -​ M2 receptors in the cardiovascular system. -​ M3, occurs in both smooth muscle and glandular tissues. Muscarinic receptors are coupled to a variety of intracellular signal transduction mechanisms that modify K+ and Ca2+ channel conductances. They can also activate nitric oxide synthase, which promotes the local release of nitric oxide in some parasympathetic target tissues However, we also have to consider that a lot of interactions between the molecules and receptors are present. For example, some cholinergic sympathetic ganglia can activate both nicotinic and muscarinic receptors to produce -​ a fast phasic response -​ a slow tonic one. Another example is in sympathetic transmission where the norepinephrine is linked to alpha 1 adrenergic receptor and alpha 2 adrenergic receptors located at the level of presynaptic tissue that allows a sort of feedback control of release of the neurotransmitter. The last is coactivation, which is on different type of receptors, for example the cotransmission that involve activation of different receptors in parasympathetic postganglionic receptors where occurs the release of Ach with muscarinic receptors and simultaneously we have the release of vasoactive intestinal peptide for the control of secretion of salivary glands. Thus different types of integration between synaptic activity and release of neurotransmitters are found. OUT OF III 1.​ Involuntary activity The ANS controls the cardiovascular function: -​ mechanical and chemoreceptors are located in specific vessels such as the carotid body, but also in cardiac muscle. -​ baroreceptors sense deformation of vessels and chemoreceptors respond to changes in blood gas level. The ANS controls the cardiovascular function. -​ mechanical and chemoreceptors located in specific vessels such as the carotid body, but also cardiac muscle. -​ baroreceptors sense deformation of vessels and chemoreceptors respond to changes in blood gas level, The information is sent through the glossopharyngeal nerve (petrosal ganglion) to the NST. The NST then sends inputs -​ to specific nucleus ambiguus (involved in control of heart), who in turn sends via vagus specific output to the cardiac plexus to control the heart. -​ to the intermediolateral visceromotor neurons in the spinal cord through the sympathetic chain which sends the information to the heart. This is done when we stand up from sitting, this would decrease the pressure, to avoid this orthostatic decrease of pressure our ANS evokes the activity of the sympathetic system to increase the heart frequency, contrast the decrease of pressure and simultaneously inhibits the drive of the parasympathetic, thus allowing us to avoid to fall down when we stand up. Bladder: The sympathetic innervation, via inferior mesenteric ganglion and ganglia of pelvic plexus can increase the activity (volume) of the bladder by inhibiting the contraction of the bladder. The parasympathetic causes the bladder emptying by acting on neurons located in sacral segments S2-S4 that innervate the visceral motor neurons and parasympathetic ganglia in the pelvic pathway. Chemo-and mechanical receptors detect when the bladder is full. The information reaches -​ the preganglionic neurons of parasympathetic system, which is activated eliciting a relax of the internal sphincter of the bladder and urination can occur. -​ to the the Barrington’s nucleus, located in the pons: the input from this nucleus can trigger that activity of alpha motoneurons controlling the voluntary contraction and relaxation of the muscles that are required for the micturition. These muscles are tonically contracted and when the afferent inputs of the volume of bladder reach the nucleus, the tonic activity is inhibited and we have the contraction of the bladder. Peristalsis: The peristalsis is driven by a stimulus which causes the relaxation of the tissue and automatically the inhibition of motoneurons close to the stimulus, then the instricin connectivity of these inhibitory motor neurons trigger the activity of excitatory motor neurons caudally and these contractions originate a unidirectional way toward the anus. This is a specific function of the enteric system, but we also have modulation of sympathetic and parasympathetic systems. ​