Homeostasis and nervous system

1. Homeostasis and nervous system

2. Behavior and homeostasis 2/16 • stimulation of the hypothalamus and limbic system induces complex motor-vegetative-endocrine reactions • these reactions serve homeostasis,reproduction or survival in dangerous situations • motor components supplement purely vegetative or humoral reactions and are indispensable for the adequate behavior • hypothalamus and limbic system is under descending, voluntary control from the neocortex – luckily... • experimental analysis of these processes is difficult: lesions, injuries, then stimulation (Hess, 1930-; Jose Delgado, 1960-), later recording, immunohistochemical analysis, local microinjection of drugs • all these would be impossible without the invention of the stereotaxis – Horsley and Clark

3. Hypothalamic neurons Nucl.dorsomedialis Nucl. posterior Commissura anterior Corp.mammillare Nucl. paraventricularis Nucl.ventromedialis Nucl. preopticus med. Nucl. anterior Nucl. arcuatus Nucl. suprachiasmaticus Nucl. supraopticus Chiasma opticus Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 17-3 Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 17-4 Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 5-15 3/16 • the three basic types of hypothalamic neurons: • large neurosecretory – n. supraopticus, n. paraventricularis – vasopressin (AVP), oxytocin (9 aa) • small neurosecretory – diffuse location, axons in eminentia mediana – CRH, TRH, GHRH, GnRH (LHRH), AVP, somatostatin, dopamine (PIF) • not neurosecretory – all the other cells, most of them release neuropeptides alone or together with other transmitters (AII, SP, neurotensin, CCK, opioids, AVP, NPY, etc.) ,  • blood-brain barrier has windows (fenestrated capillaries) – direct exchange of molecules between the blood and the neurons – circumventricular organs • eminentia mediana: releasing and inhibiting factors • neurohypophysis: AVP and oxytocin • subfornical organ (water balance), organum vasculosum (circulation): short pathway to the HT • area postrema (food uptake): long pathway to the HT 

4. Hypothalamic in- and output I. • the hypothalamus receives neuronal and humoralinputs and generates neuronal and humoral responses • theoretically it means four combinations • neuronal input – humoral response: • oxytocin secretion – during breast-feeding, stimulation of the nipple, the view and the crying of the baby stimulates, anxiety inhibits • vasopressin secretion – neurons themselves function as osmoreceptors (shrinking – hypopolarization), and: • osmoreceptors in organum vasculosum and subfornical organ • information from volume receptors • AII stimulates AIIergic neurons in the subfornical organ, projection to POA • chemoreceptive trigger zone of vomiting • warm receptors in skin increase, cold receptors decrease AVP production - urination increases in cold environment • distillated water in the mouth • alcohol inhibits AVP production – „Bier mit Schnapps” • any increase in AVP production might increase water intake – complicated behavioral response 4/16

5. Hypothalamic in- and output II. • neuronal and humoral input – humoral output • in the regulation of adenohypophysis both are present: negative feedback (humoral input), increase of CRH-AVP production in stress induced by neuronal inputs • neuronal and humoral input – neuronal output • regulation of food intake – very complicated • several hypothalamic neuropeptides, leptin from adipose tissue, etc. participates • ventromedial nucleus: after its lesion, the animal consumes more from tasty food, more intense insulin response - obesity • lateral hypothalamus: after its lesion, the animal refuses to eat the usual food, but consumes the especially tasty • before these nuclei were called satiation and hunger centers, respectively • neuronal input – neuronal output • regulation of heartbeat and circulation, e.g. fainting from fear – these reactions are emotional and can be induced from the amygdala • thermoregulation and sympathoadrenal reaction in more details 5/16

6. Thermoregulation I. 6/16 • metabolism produces heat, in warm environment we are heated up through the skin as well • homoeothermic animals have to regulate their body temperature • at rest, the largest producers of heat are the brain, heart, intestines and muscles, during exercise the muscles • 85% of heat is dissipated through the skin, 15% is lost through the lungs; heat is transported by the blood • core temperature: temperature of internal organs that also depends on the organ – blood flowing through the heart would be optimal, but difficult to measure • in the morning, after awakening and at rest it is 37.5°daily fluctuation 1°, peak early afternoon, minimum at dawn • shell temperature: skin and subcutaneous connective tissue, measured at different points

7. Heat production in the body 7/16

8. Thermoregulation II. 8/16 • core temperature can be approximated by measuring in the oral cavity or in the rectum, the armpit is less reliable • minimal heat production and dissipation in thermoneutral environment: 21-23° with clothes on, 27-30° naked • regulation is based on negative feedback, control mechanisms act according to the „control error” or ambient temperature („prediction”) • in the anterior hypothalamus warm and cold neurons detect core temperature • further receptors in the spinal cord, liver, etc. • activity of thermosensitive neurons is modified by information coming from the skin • stimulation of this area causes hypothermia, its lesion results in hyperthermia – „cooling center”

9. Thermoregulation III. 9/16 • stimulation of the posterior hypothalamus causes vasoconstriction in the skin and shivering, after its lesion hypothermia develops in cold temperature – „heating center” • in some animals cold induces T3/T4 production • brown adipose tissue in newborns and many animal species – warming, e.g. after hibernation • depending on ambient temperature, three zones can be distinguished in thermoregulation: • 31-34° - vasomotor regulation zone – evaporation, radiation is sufficient, skin circulation regulates • above 34° vasomotor-sudomotor zone: air is warmer than skin, evaporation (sweating) is the only mean, sympathetic tone ceases in skin, maximal vasodilatation helped by bradykinin from by activated sweat glands • in cold – zone of metabolic regulation: vasoconstriction is maximal, but insufficient, heat production by uncoupling in mitochondria • these are supplemented by behavioral reactions

10. Fever 10/16 • activation of immune system is accompanied by the increase of core temperature • any increase exceeding 1° is called fever, below this value, it is low fever • „reference value” increases, heat production increases – shivering • when the cause is over, intense sweating, temperature decreases • fever is induced mostly by endogenous pyrogens (e.g. IL-1) • strong relationship with sleep regulation: sleep deprivation increases reference value, cold feeling • prolonged sleep deprivation: increased reference value and increased heat dissipation – death is caused by the disturbance in energy balance

11. Alarm reaction 11/16 • under normal circumstances, sympathetic nervous system and adrenal medulla change their noradrenaline and adrenaline release as needed • in case of threat (exam), injury, physical exercise, blood loss, strong cold, etc. sympathoadrenal activation is induced – fight-or-flight, acute stress response (W.Cannon) • pupil is dilated, hears are erected, sweating increases (cold sweat), hyperglycemia and characteristic behavioral symptoms appear: in cats arching of the back, hissing, scratching • in addition to the sympathetic nervous system, adrenal medulla is also involved • adrenal medulla is built up by chromaffin cells, with chromaffin granules in columns around capillaries – sympathetic ganglion cells are of the same origin

12. Adrenal medulla 12/16 • two types of cells: adrenaline and noradrenaline producing; in humans 80:20 % ratio • tyrosine – tyrosine hydroxylase: DOPA – decarboxylation: dopamine – dopamine-β-hydroxylase: NA – enters chromaffin granule • in 80% of the cells, NA goes to the cytoplasm, receives a methyl group, reenters as adrenaline • transcription of the methylating enzyme occurres only by high glucocorticoid levels – importance of anatomical arrangement • release is regulated by preganglionic fibers through n-ACh • Adr in blood comes exclusively from here, NA (higher level!) mostly from sympathetic terminals • adrenergic effects depend on the levels and ratios, NA causes strong vasoconstriction (Adr and not NA should be injected into the heart) • Adr cannot penetrate blood-brain barrier!!

13. Adrenergic receptors 13/16

14. Control of alarm reaction 14/16 • by stimulating the lateral and posterior hypothalamus, the full alarm reaction, or its certain elements can be elicited • vegetative and behavioral reactions in cats are exactly the same as when seeing a dog • when stimulation stops, the reaction ceases immediately • hypothalamus contains the whole program • the reaction is sometimes called „sham-rage”, but it is not appropriate, as attack is always directed against a target – real rage • partial lesion of the limbic system might lead to rage reactions elicited spontaneously or by pleasant stimuli (stroking)

15. Emotions 15/16 • responses to environmental stimuli are variable – they also depend on previous experiences • stimuli obtain emotional dimensions • these functions depend on the limbic system • limbic (on the edge) cortex was named by Broca as these areas surround foramen Monroi: gyrus cinguli, gyrus parahippocampalis, gyrus dentatus, hippocampus • now we consider amygdala, septum, parts of the basal ganglia and the diencephalon as components of the limbic system • according to Papez, the limbic system is the site of emotions, now we list learning among the functions of this system as well • amygdala is most important for the development of fear reactions • while we do not know whether an animal feels fear and anxiety, its reactions resemble human reactions

16. Fear 16/16 • aversive stimuli that induce escape reactions (e.g. electric shock) increase heart rate, blood pressure, breathing, lead to secretion of NA, Adr, ACTH, glucocorticoids, and cause freezing, urination, defecation in animals • these reactions are organized by theamygdala: painful stimuli reach directly, those requiring analysis through the thalamus and cortex the amygdala • output to the brainstem, hypothalamus, cortex • conditioned fear reaction can be also developed • glutamatergic pathways are involved with GABAergic inhibitory endings on the synapses (benzodiazepines, alcohol decrease anxiety – the liquid psychiatrist) • amygdala is very important in socialization (to distinguish reward and penalty) – more important in monkeys than in humans

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18. Medial hypothalamus Nucl.dorsomedialis Nucl. posterior Commissura anterior Corp.mammillare Nucl. paraventricularis Nucl.ventromedialis Nucl. preopticus med. Nucl. anterior Nucl. arcuatus Nucl. suprachiasmaticus Nucl. supraopticus Chiasma opticus Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 17-3

19. Coronal section of hypothalamus Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 17-4

20. Windows on blood-brain barrier Blumenfeld, Sineauer Assoc. Inc., 2002, Fig. 5-15