Autonomic nervous system

Transcription

1 Autonomic nervous system

2 The Autonomic Nervous System Autonomic - from the Greek for "self-governing," functioning independently of the will (Langley, 1898) The ANS coordinates cardiovascular, respiratory, digestive, excretory and reproductive systems - Visceral afferents, interoceptive inputs, as well as projections from those parts of the CNS that control the viscera and other autonomic functions, by comparing current inputs with anticipated needs! - Visceral efferents autonomic motor neurons: Innervates smooth muscle, cardiac muscle, secretory epithelia and glands Regulates visceral functions Heart rate, blood pressure, digestion, urination, etc Rapidity and intensity in changing visceral functions: within 3-5 sec. it can increase 2x the HR within sec. the arterial pressure can be doubled

3 The ANS has three divisions: sympathetic, parasympathetic, and enteric. Enteric ANS is a system of afferent neurons, interneurons, and motor neurons that form networks of neurons called plexuses that surround GIT. Function as a separate and independent nervous system, but it is normally controlled by the CNS through sympathetic and parasympathetic fibers.

4 S & PS Divisions of the Autonomic Nervous System -work synergistically to control visceral activity and often exert antagonistic/opposite effects on the same target organs, but: -most blood vessels are innervated only by S nerves. -PS activity dominates the heart and GI tract. -exert cooperative effects on the external genitalia. Sympathetic effects -wide spread, long-lasting mobilization of the fight, flight, or fright response -activated during exercise, excitement, and emergencies -exaggerated reaction - panic attacks Parasympathetic effects - rest and digest -results in conserving energy

5 Sympathetic and parasympathetic ANS divisions -both have a two-synapse pathway 1 st preganglionic neuron in the CNS (brainstem and spinal cord and synapse with postganglionic neuron in peripheral ganglia that innervate the target cells

6 Comparison of Autonomic and Somatic Motor Systems Somatic motor system One motor neuron extends from the CNS to skeletal muscle: voluntary, direct synapse, always excitatory (Ach) N1 nicotinic receptors Axons are well myelinated, conduct impulses rapidly Autonomic nervous system Chain of two motor neurons Involuntary, two-synapsis pathway (Preganglionic & Postganglionic neurons), either excitatory or inhibitory Conduction is slower due to thinly or unmyelinated axons

7 Motor pathways of the somatic (a) & autonomic (b) nervous system

8 Anatomical differences in Sympathetic and Parasympathetic Divisions S&PS originate from different CNS regions Sympathetic = thoracolumbar division Parasympathetic = craniosacral division S&PS anatomical differences -Length of postganglionic fibers S: long postganglionic fibers PS: short postganglionic fibers -Branching of axons S: highly branched, influences many organs PS: few branches, localized effect

9 Anatomical differences in Sympathetic and Parasympathetic Divisions

10 Organization of the sympathetic and parasympathetic divisions of the ANS. The cell bodies of sympathetic preganglionic neurons (red) are in the lateral horn of the thoracic and lumbar spinal cord (T1 L3). Their axons project to paravertebral ganglia (the sympathetic chain/trunk) and prevertebral ganglia. Postganglionic neurons (blue) therefore have long projections to their targets. The cell bodies of PS preganglionic neurons (orange) are either in the brain (midbrain, pons, medulla) or in the sacral spinal cord (S2 S4). Their axons project to ganglia close to or inside the end organs. Postganglionic neurons (green) have short projections to their targets.

11 Anatomical aspects of the Sympathetic division of ANS Sympathetic Preganglionic Neurons are located in the thoracic and upper lumbar spinal cord between levels T1 and L3 in the lateral horn, between the dorsal and ventral horns. Axons from preganglionic sympathetic neurons exit the spinal cord through the ventral roots along with axons from somatic motor neurons. After entering the spinal nerves, sympathetic efferents diverge from somatic motor axons to enter the white rami communicantes (myelinated).

12 Anatomical aspects of the Sympathetic division of ANS Paravertebral Ganglia sympathetic ganglia that lie adjacent to the vertebral column and form the sympathetic trunk Axons from preganglionic neurons emerge only from levels T1 to L3, and enter the nearest sympathetic paravertebral ganglion through a white ramus, however the chain of sympathetic ganglia extends all the way from the upper part of the neck to the coccyx (here left and right sympathetic chains merge in the midline to form the coccygeal ganglion). In general, one ganglion is positioned at the level of each spinal root, but adjacent ganglia are fused in some cases: The most rostral ganglion, the superior cervical ganglion, arises from fusion of C1 to C4 ganglia and supplies the head and neck. The next two ganglia are the middle cervical ganglion, which arises from fusion of C5 and C6. The inferior cervical ganglion (C7 and C8), which is usually fused with the first thoracic (T1) ganglion to form the stellate ganglion.

13 Anatomical aspects of the Sympathetic division of ANS After entering a paravertebral ganglion, a preganglionic sympathetic axon has one or more of three fates: (1) synapse within that segmental paravertebral ganglion, (2) travel up or down the sympathetic chain to synapse within a neighboring paravertebral ganglion, or (3) enter the greater or lesser splanchnic nerve to synapse within one of the ganglia of the prevertebral plexus.

14 Anatomical aspects of the Sympathetic division of ANS The major prevertebral ganglia are named according to the arteries that they are adjacent to and include the celiac, superior mesenteric, aorticorenal, and inferior mesenteric ganglia. Each preganglionic sympathetic fiber synapses on many postganglionic sympathetic neurons that are located within one or several nearby paravertebral or prevertebral ganglia. It has been estimated that each preganglionic sympathetic neuron branches and synapses on as many as 200 postganglionic neurons, which enables the sympathetic output to have more widespread effects.

15 Parasympathetic fibers : -leave CNS through cranial n. III (pupillary sphincter and ciliary muscle of the eye), VII (lacrimal, nasal, and submandibular glands), IX (parotid gland), X (heart, lungs, esophagus, stomach, entire small intestine, proximal half of the colon, liver, gallbladder, pancreas, kidneys, and upper portions of the ureters); -additional PS fibers leave the lowermost part of the spinal cord S2-S3 spinal nerves (pelvic nerves) and occasionally S1, S4 nerves (descending colon, rectum, urinary bladder, and lower portions of the ureters). -about 75 % of all PS nerve fibers are in the vagus nerves (cr. N. X), passing to the entire thoracic and abdominal regions of the body.

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17 The visceral control system also has an important afferent pathway All internal organs are densely innervated by visceral afferents. -nociceptive (painful) inputs that travel in sympathetic nerves -mechanical and chemical (physiological) stimuli, including stretch of the heart, blood vessels, and hollow viscera, as well as PCO2, PO2, ph, blood glucose, and temperature of the skin and internal organs. Most axons from physiological receptors travel with parasympathetic fibers. Cell bodies of visceral afferent fibers are located within the dorsal root ganglia or cranial nerve ganglia (e.g., nodose and petrosal ganglia). 90% of these visceral afferents are unmyelinated. The largest concentration of visceral afferent axons can be found in the vagus nerve, which carries non-nociceptive afferent input to the CNS from all viscera of the thorax and abdomen. Most fibers in the vagus nerve are afferents, even though all parasympathetic preganglionic output (i.e., efferents) to the abdominal and thoracic viscera also travels in the vagus nerve. Vagal afferents, whose cell bodies are located in the nodose ganglion, carry information about the distention of hollow organs (e.g., blood vessels, cardiac chambers, stomach, bronchioles), blood gases (e.g., PO2, PCO2, ph from the aortic bodies), and body chemistry (e.g., glucose concentration) to the medulla.

18 Neurotransmitters of Autonomic Nervous System Neurotransmitter released by preganglionic axons Acetylcholine for both S&PS branches (cholinergic) Neurotransmitter released by postganglionic axons Sympathetic most release norepinephrine (adrenergic), also neuropeptide Y and ATP. Parasympathetic release acetylcholine, also neuropeptides (VIP)

19 Autonomic postganglionic neurons can change their transmitters phenotype! Some ANS neurons can change their transmitter phenotypes under appropriate environmental conditions, demonstrated both in vitro and in vivo phenotypic switching/plasticity: During development (e.g. innervation of sweat glands by sympathetic postganglionic neurons that are cholinergic) Postganglionic cells grown in vitro in the presence of heart conditioned medium changed from an adrenergic to a cholinergic phenotype.

20 Secretion of Acetylcholine and Norepinephrine by Postganglionic Nerve Endings Many of the PS nerve fibers and almost all the S fibers connect with the effector cells or terminate in connective tissue located adjacent to the target cells Postganglionic fibers present bulbous enlargements =varicosities, where transmitter vesicles of Ach or NE are synthesized and stored. Also in the varicosities are large numbers of mitochondria that supply ATP, required to energize Ach or NE synthesis. AP depolarization calcium ions inflow into nerve transmitter substance is secreted. Synthesis of Ach Ach acetate ion and choline, catalyzed by acetylcholinesterase (bound with collagen and glycosaminoglycans in the local connective tissue) fast end of Ach action

21 Synthesis of norepinephrine -begins in the axoplasm of the terminal adrenergic nerve endings, completed inside the secretory vesicles. Transport of dopamine into the vesicles In the adrenal medulla, this reaction goes still one step further to transform about 80 % of the NE into E: NE is removed from the secretory site by: (1) reuptake into the adrenergic nerve endings by an active transport process (50-80 % ); (2) diffusion away from the nerve endings into the surrounding body fluids and then into the blood - accounting for removal of most of the remaining NE; (3) destruction of small amounts by tissue enzymes (monoamine oxidase in the nerve endings, and catechol-o-methyl transferase, in all tissues).

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26 Signal transmission in ANS A. Sympathetic Preganglion secretes Acetylcholine (Cholinergic) Receptor on the Postganglionic neuron = Nicotinic Postganglionic neuron secretes Norepinephrine (Adrenergic), NPY, ATP, etc Target (smooth muscle, cardiac muscle, glands) Receptor = Adrenergic (α1, α2; β1, β2, β3)! Sweat glands, some blood vessels, piloerector muscle: Preganglion secretes Acetylcholine Postganglion Nicotinic receptor Postganglionic neuron secretes Acetylcholine/NO (Cholinergic/nitroxidergic) Target: -sweat gland muscarinic receptor -postganglionic fibers that innervate smooth m. in the small arteries in skeletal muscles and the brain release NO, that promotes vasodilation. Stimulation of S division has two distinctive results: - release of NE at specific locations - secretion of E and NE (4:1) into the general circulation. - alpha receptors : activated by NE > E, isoproterenol; blocked by: phenoxybenzamine - beta receptors: activated > by E; blocked by propranolol

27 Signal transmission in ANS B. Parasympathetic Preganglionic neuron secretes Acetylcholine (Cholinergic) Receptors on postganglionic neurons = Nicotinic Postganglionic neuron secretes Acetylcholine, VIP Target receptor = muscarinic (smooth muscle, heart, glands) Outflow via the Vagus Nerve (X) Fibers innervate visceral organs of the thorax and most of the abdomen (75%...) Stimulates - digestion, reduction in heart rate and blood pressure Preganglionic cell bodies Located in dorsal motor nucleus in the medulla Ganglionic neurons Confined within the walls of organs being innervated Sacral Outflow Emerges from S 2 -S 4 Innervates organs of the pelvis and lower abdomen Preganglionic cell bodies Located in visceral motor region of spinal gray matter

28 Postganglionic sympathetic and parasympathetic neurons often have muscarinic as well as nicotinic receptors Some postganglionic neurons, both sympathetic and parasympathetic, have muscarinic in addition to nicotinic receptors. At all levels of the ANS, certain neurotransmitters and postsynaptic receptors are neither cholinergic nor adrenergic. If we stimulate the release of ACh from preganglionic neurons or apply ACh to an autonomic ganglion, many postganglionic neurons exhibit both nicotinic and muscarinic responses. Because nicotinic receptors (N2) are ligand-gated ion channels, nicotinic neurotransmission causes a fast, monophasic excitatory postsynaptic potential (EPSP). In contrast, because muscarinic receptors are GPCRs, neurotransmission by this route leads to a slower electrical response that can be either inhibitory or excitatory. Thus, depending on the ganglion, the result is a multiphasic postsynaptic response that can be a combination of a fast EPSP through a nicotinic receptor plus either a slow EPSP or a slow inhibitory postsynaptic potential (IPSP) through a muscarinic receptor.

29 An example of dual nicotinic and muscarinic neurotransmission between sympathetic preganglionic and postganglionic neurons. A, Stimulation of a frog preganglionic sympathetic neuron releases ACh, which triggers a fast EPSP (due to activation of nicotinic receptors on the postganglionic sympathetic neuron), followed by a slow EPSP (due to activation of muscarinic receptors on the postganglionic neuron). B, In a rat sympathetic postganglionic neuron, the M current (mediated by a K+ channel) is normally active, hyperpolarizing the neuron. Thus, injecting current elicits only a single action potential. C, In the same experiment as in B, adding muscarine stimulates a muscarinic receptor (i.e., GPCR) and triggers a signal-transduction cascade that blocks the M current. One result is a steady-state depolarization of the cell. Injecting current now elicits a train of action potentials.

30 Nonclassic transmitters can be released at each level of the ANS

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33 Central Control of the ANS Control by the brain stem and spinal cord Reflex activity is mediated by spinal cord and brain stem (medullary centers). Reticular formation exerts most direct influence Medulla oblongata Periaqueductal gray matter Control by the hypothalamus and amygdala Hypothalamus the main integration center of the ANS that interact with both higher and lower centers to orchestrate autonomic, somatic and endocrine responses. Amygdala main limbic region for emotions Control by the cerebral cortex of the autonomic functioning via connections with the limbic system

34 Basic Structure of a Visceral Reflex 2 nd processing center Visceral reflex: Visceral sensory and autonomic neurons Participate in visceral reflex arcs -PS reflexes include : gastric and intestinal reflexes, defecation, urination, direct light reflexes, swallowing reflex, coughing reflex, baroreceptor reflex and sexual arousal. -S reflexes: cardioaccelaratory reflex, vasomotor reflex, pupillary reflex and ejaculation in males.

35 A variety of brainstem nuclei provide basic control of the ANS One of the most important lower brainstem structures is the nucleus tractus solitarii (NTS) in the medulla. The NTS contains second-order sensory neurons that receive all input from peripheral chemoreceptors and baroreceptors input, as well as nonnociceptive afferent input from every organ of the thorax and abdomen. Visceral afferents from the vagus nerve make their first synapse within the NTS, where they combine with other visceral (largely unconscious) afferent impulses derived from the glossopharyngeal (CN IX), facial (CN VII), and trigeminal (CN V) nerves. These visceral afferents form a large bundle of nerve fibers the tractus solitarius that the NTS surrounds. Afferent input is distributed to the NTS in a viscerotopic manner, with major subnuclei devoted to respiratory, cardiovascular, gustatory, and GI input. The NTS also receives input and sends output to many other CNS regions including the brainstem nuclei described above as well as the hypothalamus and the forebrain.

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37 Hypothalamus (HT) - part of diencephalon (1% of brain volume), located within the walls & floor of 3 rd ventricle, constitutes an integrative center essential for survival & reproduction, that regulates and controls the complex interactions between physiology and behavior (temperature regulation, heart rate, blood pressure, blood osmolarity, food and water intake, emotion and sex drives). - structure cytoarchitecture neurochemistry functional specializations (e.g., appetite, weight control, water balance, autonomic control, reproductive function, emotional behavior) - reciprocal connections with -almost every major subdivision of the CNS (bidirectional) -peripheral organ systems by converting synaptic information to hormonal signals (neuroendocrine regulation) - Here in this well concealed spot, almost to be covered with a thumb nail, lies the very mainspring of primitive existence vegetative, emotional, reproductive- on which, with more or less success, man has come to superimpose a cortex of inhibitions. (Cushing, 1929).

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39 HT Cytoarchitecture HT is organized into 3 longitudinal columns on either side of the 3 rd ventricle, that extend through the entire rostrocaudal extent of the HT periventricular (suprachiasmatic and arcuate nuclei), medial (contains distinct nuclei), lateral (neurons diffusely distributed)

40 Functional organization - Integrative processing in the HT HT: Brain-periphery interconnections: nervous, hormonal HT receive: Monosynaptic projections, such as first-order information from the periphery (vision) Multisynaptic cerebral pathways (limbic projections) HT integrate information HT regulatory outputs on physiology and behavior: hormonal and synaptic

41 Functional organization - Integrative processing in the HT HT & Visceral sensation -Sensory information (visceral, CV, respiratory, taste): topographically organized input through cranial nerves X & IX nucleus of solitary tract (NST) of the caudal brain stem ascending direct projections to paraventricular HT nucleus (PVH) & lateral HT area (LHA) Nucleus tractus solitarii (NST) coordinates reflex regulation of peripheral organ function -send processed sensory information to forebrain nuclei, to be integrated in the control of more complex physiological processes and behaviors. -together with the parabrachial nucleus relay splanchnic visceral and nociceptive sensory information from the spinal cord - indirect projections to HT through ventrolateral medulla and parabrachial nucleus in the pons - many of these projections are bidirectional - connections with amygdala, stria terminalis, insular cortex interoceptive sensory feedback that influences autonomic and endocrine outputs of HT homeostasis, mood! Stress induces activation of the autonomic and endocrine axes

42 HT & Central integration of autonomic function descending projection from the HT to autonomic cell groups in the brainstem and spinal cord exerts a strong influence upon the S (thoracic) and PS (cranial-lumbosacral) divisions of the ANS there are also indirect influences from HT cell groups on preganglionic neurons of the spinal cord Coordination of autonomic functions and behavioral responses to environmental challenges coordinates the the wisdom of the body (Cannon, 1937): tissue-, organ-, and system-level integration of the body s physiology to achieve homeostasis and support behavior; continuous and automatically.

43 HT & immune function & thermoregulation HT influences immune system through neuroendocrine and autonomic outputs: - activity of immune cells of the spleen is influenced directly by synaptic-like contacts of NA neurons of the sympathetic ANS - immune system activation fever - HT neurons stimulate or inhibit heat production: heat sensitive neurons in the medial preoptic area act to reduce core body temperature by inhibiting other neurons in the HT and caudal brainstem to induce thermogenesis - nonshivering thermogenesis in small animals is achieved through the activation of sympathetic activation of brown adipose tissue (BAT)- its mitochondria converts energy from fatty acids metabolism into heat There is a considerable overlap of cell groups that regulate energy balance, stress and fever!