BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 1 Terms you should understand: autonomic nervous system, sympathetic nervous system, parasympathetic nervous system, ganglion (ganglia), preganglionic neuron, postganglionic neuron, vagus nerve, cholinergic, nicotinic receptor, muscarinic receptor, adrenergic, epinephrine (Epi), norepinephrine (NorEpi), α-adrenergic receptor, ß-adrenergic receptor, agonist, d-tubocurarine, α- Bungarotoxin, atropine, adrenal medulla, limbic system, solitary nucleus, vagus nerve, hypothalamus (lateral and ventromedial), aphagia, hyperphagia, amygdala, cingulate gyrus, frontal cortex. I. The two divisions of the autonomic nervous system (sympathetic and parasympathetic) supply most of the nervous control for the involuntary ("vegetative" or “visceral”) functions of the body. They are a second efferent system (in addition to "voluntary" motor output from brain and spinal cord), sending signals that modulate activity of glands or muscles, usually smooth muscles. A. These two systems work together to produce homeostasis; e.g., the balance between the two systems keeps blood pressure, body temperature, and acid-base balance constant. B. Both branches of the autonomic nervous system consist of a two-neuron chain between the central nervous system and the periphery. The somata of the pre-ganglionic neurons in both branches of the autonomic nervous system lie within the brain or the spinal cord. Autonomic nervous system Somatic motor Sympathetic Parasympathetic Central nervous system Sympathetic Fig. 7.1 Peripheral chain nervous ganglion system Parasympathetic (near spinal gangion cord) (near taraget) Target Skeletal Smooth and cardiac muscle; glands muscle C. Preganglionic neurons (somata inside the CNS) synapse with postganglionic neurons (somata outside the CNS). 1. Sympathetic postganglionic cell bodies are in ganglia near the CNS. Most of them are in the chain of sympathetic ganglia that runs along either side of the spinal cord. 2. Parasympathetic postganglionic cell bodies lie in ganglia near the organ innervated. 3. Postganglionic neurons in both systems synapse onto the end organs: e.g., smooth muscles, cardiac muscle fibers, endocrine glands, exocrine glands to control such functions as heart rate, digestion, respiration rate, salivation, perspiration, urination, sexual arousal. 4. Strongly tied to our emotions: some argue that autonomic responses cause emotional responses. BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 2 Fig. 7.2. Comparison of the anatomy of the sympathetic and skeletal efferents. Fig. 7.3. Locations of some sympathetic and parasympathetic ganglia. (Fig. 11-5 in Silverthorn, 5th Ed.) BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 3 D. Many functions of the sympathetic nervous system are related to mobilization for activity and/or emergencies (“fight or flight”); it is an arousal system. 1. Sympathetic preganglionic neurons are cholinergic; i.e., they release ACh. a. The receptors on the postganglionic neurons are excited by ACh. b. They are also excited by nicotine. Therefore, these receptors are said to be nicotinic receptors. (Receptors at the neuromuscular junction are also nicotinic.) 2. Most sympathetic postganglionic neurons are adrenergic; i.e., they release norepinephrine (NorEpi; aka noradrenaline) with a little epinephrine (Epi; aka adrenaline) included. (A few postganglionic sympathetic neurons are cholinergic, e.g., neurons that innervate sweat glands.) a. The targets of postganglionic sympathetic neurons have on their cell membranes receptors for norepinephrine, called adrenergic receptors. b. There are several types of adrenergic receptors; the two major classes are: i . α-adrenergic receptors: higher binding affinity for NorEpi ii. ß-adrenergic receptors: higher binding affinity for Epi iii. These receptors usually have opposite effects on end organs; e.g., α-adrenergic receptors constrict most blood vessels and ß-adrenergic receptors dilate them, by contracting (α- adrenergic) and relaxing (ß-adrenergic) the smooth muscles in the walls the blood vessels. Fig. 7.4. Transmitters and receptors in the sympathetic and parasympathetic pathways. (Fig. 11-7 in Silverthorn, 5th Ed.) 3. Increased activity in sympathetic the sympathetic nervous system produces many whole-body effects consistent with a mobilization function. a. Heart rate and vigor of cardiac contraction increases. b. Blood pressure increases because the smooth muscles in the walls of blood vessels contract. c. Gut motility and blood flow to the gut decreases. d. The liver releases glucose into the blood, making it available to working muscles. E. Many parasympathetic functions support and augment vegetative functions, such as digestion. 1. Preganglionic parasympathetic neurons are nicotinic cholinergic. BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 4 2. Postganglionic parasympathetic neurons are also cholinergic, but the receptors on their targets are insensitive to nicotine. a. Instead, they are excited by muscarine, a toxin from a toadstool. These receptors are, therefore, called muscarinic receptors. i. They respond to many other agonists (substances that mimic the effects of the natural transmitter) that have no effect on nicotinic receptors. ii. They are metabotropic: ACh bind to the receptor activates second messenger systems, much more like the cellular effects of hormonal signaling. b. Muscarine has no effect on the neuromuscular junction or on the preganglionic-to- postganglionic cell synapse in either branch of the autonomic nervous system. c. Parasympathetic activity produces its vegetative functions because the target organs have muscarinic receptors. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Comparison of the pharmacology of autonomic synapses Preganglionic Postganglionic Postganglionic Receptors on transmitter receptors transmitter target organs Sympathetic Acetylcholine Nicotinic Norepinephrine Adrenergic branch cholinergic (a catecholamine) (either α or β) Para- Acetylcholine Nicotinic Acetylcholine Muscarinic sympathetic cholinergic cholinergic branch Spinal cord Ganglion Target Some useful blockers to know about: d-tubocurarine (an active agent in the poison called curare)--blocks primarily nicotinic AChRs α-Bungarotoxin--blocks ONLY nicotinic AChRs atropine--blocks muscarinic AChRs, but not nicotinic AChRs ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ F. In normal life, the sympathetic and parasympathetic systems work in active opposition to one another. The state of the animal at any particular time reflects the balance between them. Under normal conditions, neither system is turned fully off or turned fully on. 1. Autonomic control is involuntary and automatic (e.g., you cannot decide that your gut will increase its peristaltic movements). a. Control by the autonomic nervous system depends on reflex arcs, similar to the stretch reflex. i. Sensory receptors for most autonomic reflexes are found in the viscera; they respond to signals like blood pressure or stretch of the gut wall. ii. There may be several layers of interneurons. iii. The output is always a preganglionic neuron that synapses onto a postganglionic neuron, which synapses onto the target. BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 5 b. The autonomic nervous system works in coordination with the adrenal medulla. i. Neurons in the brain excite adrenal medullary cells using nicotininc cholinergic synapses. ii. The adrenal medullary cells release Epi into the blood stream, where it binds to ß2-adrenergic receptors in blood vessel muscle cells, causing them to relax. iii. The Epi is also carried to other tissues and organs (e.g., heart, adipose tissue). iv. The adrenal medulla is like a sympathetic ganglion, with a HUGE synaptic cleft. Fig. 7.5. Summary of the functions of the autonomic nervous system and the adrenal medulla. 2. Control of the output of the two systems lies within several nuclei in the "lower" part of the brain, particularly around the hypothalamus and in the brain stem. a. The solitary nucleus in the brain stem is an important center for the integration of visceral sensory information. b. Other nuclei in the brain stem serve either sensory or motor roles in autonomic control. For example, the motor nucleus of the vagus nerve contains many parasympathetic preganglionic neurons. BIPN100 F15 Human Physiol I Lecture 7: Autonomic Nervous System & Limbic System p. 6 3. The hypothalamus, which consists of many nuclei, acts as the "head ganglion" of the autonomic nervous system. (It also has crucially important endocrine functions as well.) Fig. 7.6. Functional anatomy of the hypothalamus. a. Stimulating defined regions of the hypothalamus produces coordinated somatic responses. For example, stimulating a cat’s lateral hypothalamus increases blood pressure, raises body hair, constricts pupils, arches the back, and raises the tail - all characteristic of anger. b. Lesioning the lateral hypothalamus: the cat cannot be provoked to display anger. c. Motivational states (e.g., hunger and thirst) are mediated by neurons in the hypothalamus. i. Lesions of the lateral hypothalamus (LH) cause aphagia - total loss of appetite. Stimulation in this region causes feeding. The LH has been termed the “hunger center”. ii. Lesions in the ventromedial hypothalamus (VMH) cause hyperphagia and gross obesity.