B. Osmund. California State University, San Marcos.

Moreover solian 50mg line, there is extensive evidence that anti-anxiety drugs prevent activation of the behavioural inhibition system by blunting monoaminergic transmission in the hippocampus best solian 100 mg. This comprises the amygdala generic 100 mg solian amex, hypothalamus and central grey in the midbrain 100 mg solian sale. It is generally agreed that the periaquaductal grey area (PAG) of the central grey is responsible for eliciting the flight/fight response which incorporates autonomic changes and analgesia as well as the locomotor response cheap solian 50 mg amex. Gray (1987) proposes that the central grey is normally inhibited by the (ventromedial) hypo- thalamus and that the influence of the hypothalamus is governed in opposing ways by the behavioural inhibition system and the amygdala. Whereas the former augments hypothalamic inhibition of the flight/fight response, the latter inhibits it, thereby releasing the flight/fight response (Fig. The amygdala is thought to be a major target for conditioned sensory inputs and to organise the con- ditioned fear response (LeDoux and Muller 1997); this is effected by its connections to the hypothalamus and PAG. Serotonergic neurons, originating in the dorsal Raphe nucleus (DRN), innervate both the amygdala and the PAG. In the former region, they are thought to augment active avoidance of aversive signals by exaggerating the amygdalar response to conditioned aversive stimuli (Deakin and Graeff 1991; Graeff et al. This response could be modulated, at the level of both the DRN and the amygdala, by neuronal inputs from both the frontal ANXIETY 417 Figure 19. Inputs from the behavioural inhibition system also augment the activity of the (ventromedial) hypothalamus which suppresses the flight/ fight response generated in the periaquaductal grey. In contrast, the amygdala inhibits hypothalamic activity and releases the flight/fight response. Anti-anxiety drugs are thought to inhibit monoaminergic activation of the behavioural inhibition system cortex, which is thought to process the perception of sensory information, and the hippocampus, which processes contextual (environmental) cues. Deakin and Graeff (1991) further propose the existence of a pathway, again arising in the DRN, which inhibits activation of the PAG. It is suggested that a reduction of serotonergic transmission in this area releases the flight/fight response. Under normal conditions, activity in this system is governed by higher centres in the forebrain (the cortex and hippocampus) so that, when interpretation of prevailing stimuli deems it appropriate, the flight/fight response is suppressed. A deficit in serotonergic inhibition of the PAG is thought to be the origin of panic. For instance, during low arousal states, a decline in the activity of forebrain serotonergic systems would diminish the inhibition of the PAG. This would ensure that threatening stimuli would evoke a protective escape response by default until cortical systems switch off the PAG response, if appropriate, as arousal increases (Handley 1995). It could also explain why patients often report that they are woken up during the night by their panic attacks. This system comprises the amygdala, hypothalamus and periaquaductal grey (PAG) and coordinates behavioural and neuroendocrine responses to conditioned and unconditioned aversive stimuli. Activity within the defence system is governed by higher centres, such as the frontal cortex and hippocampus. Serotonergic neurons projecting from the dorsal Raphe nucleus are proposed to activate the amygdala (‡) thereby promoting the response to conditioned aversive stimuli (anxiety). Projections from this nucleus to the dorsal and ventral periaquaductal grey (dPAG and vPAG) are thought to suppress (7) the flight/fight response to aversive stimuli. A deficit in serotonergic transmission to this brain region is thought to underlie panic. Possible targets for anti-anxiety drugs, acting via the GABAA receptor, are indicated by the dotted arrows. See text for further details There is a good deal of evidence that postsynaptic 5-HT2A/2C receptors mediate the actions of 5-HT in both the amygdala and the PAG (Deakin, Graeff and Guimaraes 1992). Thus local infusion of 5-HT2A/2C antagonists into the amygdala has an anti- conflict effect in animals while their systemic administration might have (albeit controversially) anti-anxiety effects in humans. In contrast, these drugs promote the flight/fight response to aversive stimuli. This leads to the prediction that drugs that relieve anxiety, through inhibition of 5-HT transmission in the amygdala, will exacerbate panic by inhibiting the restraining influence of 5-HT in the PAG. In fact, this has been offered as an explanation for the panic attacks experienced by some patients given buspirone.

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Two isoforms of the receptor were identified which differed only in the length of their amino-terminals Ð these were termed GABABR1a (960 amino acids) and GABABR1b (844 amino acids) purchase 100 mg solian with amex. Additional isoforms purchase solian 50 mg line,both termed GABABRIc generic solian 50mg mastercard,have also been identified in rat (Pfaff et al order 50mg solian amex. Each protein has a predicted structure consisting of a large N-terminal and seven transmembrane domains buy discount solian 50 mg online,similar to metabotropic glutamate receptors. The cloned receptors,when expressed in cell lines and studied by radioligand binding assays,showed some of the expected pharmacology of GABAB receptors. However,the affinity of agonists was much lower than seen with native receptors and not all expected coupling to effector systems could be demonstrated (possibly because of inappropriate or inefficient linkage to G-proteins). Subsequently,a second receptor protein, GABABR2,was identified (Jones et al. GABABR1 AMINO ACIDS: INHIBITORY 243 244 NEUROTRANSMITTERS,DRUGS AND BRAIN FUNCTION and GABABR2 are found in areas of the brain known to contain GABAB receptors, including hippocampus,cerebellum and cortex,but some differences in their distribution suggest that in certain cases homomeric GABABRs may be functional or that dimerisation may occur with other unidentified GABABRs (Bowery and Enna 2000). The existence of structurally and pharmacologically distinct pre- and postsynaptic GABAB receptors is supported by the recent demonstration that gabapentin,an anticonvulsant GABA analog,is a selective agonist for postsynaptic GABA R1a/R2 heterodimers coupled to K‡ channels (Ng et al. B GABAC RECEPTORS Early studies of the action of GABA and its analogues on spinal neurons revealed that the depressant action of one of these, cis-4-aminocrotonic acid (CACA),was not blocked by bicuculline. Several analogues of GABA shared the same properties and did not interact with the then newly described GABAB receptors. In 1984,the term GABAC was introduced to distinguish this third class of GABA receptor (Johnston 1996). Like GABA receptors,GABA receptors activate anion channels permeable to ClÀ (and A C HCO À) and the responses are similarly governed by the distribution of ClÀ across the 3 neuronal membrane. GABAC RECEPTOR PHARMACOLOGY GABAC receptors are defined by their insensitivity to bicuculline and their activation by conformationally restricted analogues of GABA such as CACA and (‡)-CAMP (1S,2R-2-(aminomethyl)cyclopropanecarboxylic acid). They are blocked by picrotoxin but can be selectively antagonised by TPMPA (1,2,5,6-tetrahydropyridin4-ylphosphinic acid). Unlike GABAA receptors,they are not affected by benzodiazepines,barbiturates or anaesthetics (Barnard et al. STRUCTURE OF GABAC RECEPTORS The best evidence for the existence of functional GABAC receptors and the clearest indication as to their molecular identity comes from work on the retina. Expression of retinal mRNA in Xenopus oocytes produces GABA-gated chloride channels with conventional GABAA receptor pharmacology as well as channels with characteristics of GABAC receptors (i. The basis of this distinction was made clear with the cloning from a retinal cDNA library of a new GABA receptor subunit termed r (Cutting et al. Originally classed as GABAA subunits,with which they have $35% sequence identity,they are now accepted as a distinct group of subunits,forming the basis of the relatively simple,and evolutionarily older,GABAC receptors. Unlike subunits of the GABAA receptor, r subunits form fully functional homomeric receptors and do not co-assemble with a or b subunits. These homomeric receptors are similar to native GABAC receptors,in that they are activated by GABA and CACA,blocked by picrotoxin and TPMPA but not bicuculline,and unaffected by barbiturates,benzodiazepines or anaesthetics (Fig. Receptors formed from r subunits have a higher affinity for GABA than many GABAA receptors formed from abg combinations,have a lower single-channel conductance and produce currents that decay more slowly after removal of GABA. Picrotoxinin is the active component of picrotoxin and also acts at GABAA receptors. The receptors can form as homomeric assemblies of r subunits but native receptors may be heteromeric assemblies of r subunits (e. Activation of these presynaptic receptors inhibits glutamate release from the bipolar cells. However,the true molecular composition of native GABAC receptors is still under investigation. While homomeric receptors formed from r subunits share many features of retinal GABAC receptors,a number of discrepancies have been noted in the details of ion permeability, single-channel conductance and channel open time (Wotring,Chang and Weiss 1999). Thus,it has been suggested that native GABAC receptors may be composed of heteromeric assemblies of r subunits or,in certain cases,that such assemblies may also contain a g2 subunit (Qian and Ripps 1999). All three r subunits have been identified in brain,but their precise location and the functional significance of this expression is unclear. In particular,the basis of GABAC receptor-like responses seen,for example,in the spinal cord,cerebellum,optic tectum and hippocampus is yet to be determined. It is involved in many metabolic pathways,is an essential component of proteins,and is found throughout the brain.

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The reflex arc enables a rapid cheap solian 50 mg mastercard, automatic Review Activities Objective Questions 7 solian 100mg on-line. A person with quadriplegia from a spinal (b) It contains components of the (e) the sacral plexus cord injury at the level of C5 can speak buy cheap solian 100 mg online, autonomic nervous system discount 100 mg solian otc. Roots solian 100mg fast delivery, trunks, divisions, and cords are digest food, breath, and regulate his or her (c) Sensory receptors, nerves, ganglia, characteristic of heartbeat, yet the person cannot move and plexuses are all part of the PNS. Which cranial nerve innervates the (c) axillary/brachial appointment with the company doctor muscle that raises the upper eyelid? Following a routine physical exam, (b) the oculomotor nerve ligament is tapped is an example of the physician scheduled the man for a (c) the abducens nerve (a) a visceral reflex. Discuss (b) the facial nerve Essay Questions the possible treatment of this condition. Explain the structural and functional (You may have to refer to medical (d) the vagus nerve relationships between the central nervous textbooks in your library to find the system, the autonomic nervous system, answer. Which cranial nerve passes through the and the peripheral nervous system. List the cranial nerves and describe the punch during the world featherweight (a) the facial nerve major function(s) of each. How is each championship fight, the ringside (b) the glossopharyngeal nerve cranial nerve tested for dysfunction? List the roots of each of the spinal damage when his right zygomatic bone 6. Describe where each plexus is located and state the nerves that originate symptoms might the boxer have displayed fibers? Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Autonomic Nervous System 13 Introduction to the Autonomic Nervous System 435 Structure of the Autonomic Nervous System 438 Functions of the Autonomic Nervous System 444 Control of the Autonomic Nervous System by Higher Brain Centers 448 CLINICAL CONSIDERATIONS 450 Clinical Case Study Answer 451 Chapter Summary 451 Review Activities 452 Clinical Case Study A low-flying crop duster sprays a field worker. Within the hour, he develops blurry vision, ex- cessive salivation, and a runny nose. As the minutes pass, he begins to experience nausea, vom- iting, abdominal cramping, and coughing up of copious mucus. An observant paramedic called to the scene makes a diagnosis of organophosphate poisoning and promptly initiates therapy. Can you account for each of the symptoms this man suffered by describing the normal response of individual organs to parasympathetic stimuli? What effect would this drug have on the eyes, salivary glands, and nose? FIGURE: Because many pesticides are neurotoxins that can be readily absorbed through the skin and mucous membranes, caution must always be taken when using these poisons. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 Chapter 13 Autonomic Nervous System 435 Autonomic motor nerves innervate organs whose functions INTRODUCTION TO THE are not usually under voluntary control. The effectors that re- AUTONOMIC NERVOUS SYSTEM spond to autonomic regulation include cardiac muscle tissue (within the heart), smooth muscle tissue (within the viscera), The action of effectors (muscle tissue and glandular epithelium) is and glandular epithelium. These effectors are part of the organs controlled to a large extent by motor neuron impulses. Skeletal of the viscera, of blood vessels, and of specialized structures muscles, which are the voluntary effectors, are regulated by so- within other organs. The involuntary effectors (smooth muscle vation contrast with the voluntary control of skeletal muscles by tissue, cardiac muscle tissue, and glandular epithelium) are regu- way of somatic motor innervation. The traditional distinction between the somatic system and the autonomic nervous system is based on the fact that the Objective 1 Define the terms preganglionic neuron and former is under conscious control whereas the latter is not. Recently, postganglionic neuron and explain how the motor pathways however, it has been discovered that we have the remarkable ability of the somatic motor and autonomic motor systems differ. This “discovery” comes as old news to Indian yogis, who have been exploiting this ability for generations. Objective 2 Explain how the autonomic innervation of involuntary effectors differs from the innervation of Unlike the somatic motor system, in which impulses are skeletal muscle. Rather than directly innervat- ing the effector organ, the axon of this neuron synapses with a sec- Organization of the Autonomic ond neuron within an autonomic ganglion. The autonomic portion of the nervous system is concerned with The second neuron in this pathway, called a postganglionic, or maintaining homeostasis within the body by increasing or de- creasing the activity of various organs in response to changing physiological conditions. Although the autonomic nervous sys- tem (ANS) is composed of portions of both the central nervous viscera: L. Autonomic Nervous © The McGraw−Hill Anatomy, Sixth Edition Coordination System Companies, 2001 436 Unit 5 Integration and Coordination FIGURE 13.

Only a few of the many clinical considerations of the cen- tral nervous system will be discussed here order solian 50mg. These include neuro- Creek logical assessment and drugs 100 mg solian fast delivery, developmental problems buy solian 50mg with visa, injuries solian 100mg cheap, (a) infections and diseases purchase 100mg solian, and degenerative disorders. Third lumbar vertebra Neurological Assessment and Drugs Coccyx Spinal cord Neurological assessment has become exceedingly sophisticated and accurate in the past few years. In a basic physical examination, only the reflexes and sensory functions are assessed. But if the physician suspects abnormalities involving the nervous system, further neuro- logical tests may be done, employing the following techniques. A lumbar puncture is performed by inserting a fine needle (b) Sacrum Subarachnoid Dura mater between the third and fourth lumbar vertebrae and withdrawing space Inserted a sample of CSF from the subarachnoid space (fig. A cis- needle ternal puncture is similar to a lumbar puncture except that the CSF is withdrawn from a cisterna at the base of the skull, near FIGURE 11. The pressure of the CSF, which is nor- needle between the third and fourth lumbar vertebrae (L3–L4) and mally about 10 mmHg, is measured with a manometer. Samples of (b) withdrawing cerebrospinal fluid from the subarachnoid space. In addi- tion, excessive fluid, accumulated as a result of disease or trauma, may be drained. With that speed, body functions as well as The condition of the arteries of the brain can be deter- structures may be studied. These types of data are important in detecting nique, a radiopaque substance is injected into the common early symptoms of a stroke or other disorders. Aneurysms and vascular constrictions or displacements by ply by examining brain-wave patterns using an electroen- tumors may then be revealed on radiographs. Sensitive electrodes placed on the The development of the CT scanner, or computerized scalp record particular EEG patterns being emitted from evoked axial tomographic scanner, has revolutionized the diagnosis of cerebral activity. The CT scanner projects a sharply focused, de- patients to predict seizures and to determine proper drug therapy, tailed tomogram, or cross section, of a patient’s brain onto a tele- and also to monitor comatose patients. The versatile CT scanner allows quick and The fact that the nervous system is extremely sensitive to accurate diagnoses of tumors, aneurysms, blood clots, and hemor- various drugs is fortunate; at the same time, this sensitivity has rhage. The CT scanner may also be used to detect certain types potential for disaster. Drug abuse is a major clinical concern be- of birth defects, brain damage, scar tissue, and evidence of old or cause of the addictive and devastating effect that certain drugs recent strokes. Much has been written on drug A machine with even greater potential than the CT scan- abuse, and it is beyond the scope of this text to elaborate on the ner is the DSR, or dynamic spatial reconstructor. A positive aspect of drugs is their administration CT scanner, the DSR is computerized to transform radiographs in medicine to temporarily interrupt the passage or perception of into composite video images. Injecting an anesthetic drug near a nerve, as in dimensional view is obtained, and the image is produced much dentistry, desensitizes a specific area and causes a nerve faster than with the CT scanner. Nerve blocks of a limited extent occur if an appendage is cross-sectional images in 5 seconds, whereas the CT scanner can cooled or if a nerve is compressed for a period of time. Nervous Tissue and the © The McGraw−Hill Anatomy, Sixth Edition Coordination Central Nervous System Companies, 2001 392 Unit 5 Integration and Coordination discovery of pharmacological drugs, physicians would frequently German measles, and excessive irradiation of the fetus are all cool an affected appendage with ice or snow before performing commonly associated with mental retardation. A local anesthetic causes a nerve block by desensi- tizing a specific area. Injuries Although the brain and spinal cord seem to be well protected within a bony encasement, they are sensitive organs, highly sus- Developmental Problems ceptible to injury. Congenital malformations of the CNS are common and fre- Certain symptomatic terms are used when determining quently involve overlying bone, muscle, and connective tissue. Headaches are the most com- The more severe abnormalities make life impossible, and the mon ailment of the CNS. Most headaches are due to dilated less severe malformations frequently result in functional disabil- blood vessels within the meninges of the brain. Neurological malformations usually have a genetic basis, generally symptomatic of brain disorders; rather, they tend to be but they also may result from environmental factors such as associated with physiological stress, eyestrain, or fatigue. Some tent and intense headaches may indicate a more serious problem, of these malformations were briefly described in the previous such as a brain tumor. It is not known why only 5%–10% of the tebral elements and may or may not involve the spinal cord.

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