BMS Endocrinology John Morris
HYPOTHALAMIC/CENTRAL CONTROL OF AUTONOMIC NERVOUS SYSTEM
The hypothalamus acts as integrative centre for regulation of the autonomic nervous system by the cerebrum, by feedback, and
from its own intrinsic sensitivity. It is involved in homeostasis; stress responses; anticipatory responses; part of integrated
somatic/endocrine/autonomic responses.
Sympathetic and parasympathetic are essentially output systems; there are also visceral afferents which are important in both
physiological regulation of and pain from the viscera; and the enteric nervous system which integrates control along the gut.
Functionally: Sympathetic: response to injury or potential injury; ‘fight or flight’
Parasympathetic: active when well-fed, warm, with 'good friend'; ‘rest and digest’
Both systems can be activated by: extrinsic (e.g. pain) and intrinsic (e.g. BP) stimuli, analysed via 'limbic system'; by psychic
activity (e.g. anxiety - tachycardia; shyness - blushing; favourite food - salivation; erotic material - vascular changes in genitalia;
anxiety - block of milk ejection, menstrual cycle).
PERIPHERAL AUTONOMIC SYSTEM (brief revision of the main points of the systems)
A. Autonomic efferent systems
1. Sympathetic system
preganglionic neurons: spinal cord T1-L2,3
sympathetic ganglia: chain from base of skull to end of sacrum
 inputs: preganglionic axons from thoraco-lumbar cord
 outputs: from all levels of the sympathetic chain
 distribution: postganglionic fibres to head, trunk, limbs;
preganglionic fibres via midline ganglia to viscera
 neurotransmitters: preganglionic: ACh (nicotinic)
postganglionic: NA, ACh, peptides
 receptors: α & β types and subtypes - effects of drugs
2. Parasympathetic system
preganglionic neurons: Cranial nns III, VII, IX, X; sacral cord S2-4
ganglia in or near targets; short postganglionic axons
 distribution: to head via ganglia:
- ciliary (III) - globe of eye: pupillary sphincter, ciliary muscle
- sphenopalatine (VII) - hard palate, nose, lacrimal gland
- submandibular (VII) - submandibular and sublingual salivary
- otic (IX) - parotid;
NB Cranial parasympathetic ganglia also act as distribution centres for
sensory (V) and postganglionic sympathetic nerves
 distribution: to viscera via vagus (X); pelvic parasympathetics
- X supplies forgut and midgut derivatives; kidneys
- pelvic parasympathetic (S2,3,4) supplies hindgut, pelvic organs.
 neurotransmitters: muscarinic ACh, peptides - effects of drugs
3. Enteric system
 neurons and plexuses in alimentary tract wall; intrinsic reflexes of gut
 inputs from sympathetic and parasympathetic axons modulate activity
 neurotransmitters: ACh, amines, peptides, ATP
B. Visceral afferents:
 receptors in gut, lung, cardiovascular
 sensitivities - distension, pain
 routes of axon projection to the CNS - physiological via IX, X, S2-4
- pain via sympathetic pathways
 projection to nucleus of tractus solitarius
Further reading:
Donadio V et al (2009) J Neurol Neurosurg Psychiatry on line.Autonomic
innervations in multiple system atrophy and pure autonomic failure.
Kaufmann H et al (2010) Neurology 74:536 Pure autonomic failure: a
restricted Lewy body synucleinopathy or early Parkinson disease?
CNS CENTRES CONTROLLING THE ANS
Hierarchical organisation of parts:
spinal cord, medulla, pons, hypothalamus, cerebral cortex.
SPINAL CORD:
spinal shock: causes absent reflexes, low BP; reflexes start to return and
BP rises, but reflexes are segmental; if cord then lesioned BP falls
again and does not recover. Very difficult to demonstrate
coordination in absence of higher centres.
sacral centres control bladder, rectum, genitalia (erection, emission;
ejaculation (requires somatic (pudendal) nerve)); role oxytocin
automatic bladder/rectum - after spinal cord injury the bladder/rectum
fills to a certain volume, then discharges.
mass reflex: a minor sensory stimulus can cause limb withdrawal,
sweating, defaecation., micturition. Probable cause: lack of
inhibition from higher centres, sprouting of dorsal roots, denervation
hypersensitivity.
Cilio-spinal centre C8,T1- this determines the sympathetic (dilator)
action on the pupil.
MEDULLA: centres which control autonomic output for
 cardiac (pressor and depressor),
 respiratory (inspiratory, expiratory, pneumotaxic),
 salivation (superior (VII), inferior (IX));
 vomiting (swallowing);
 control of blood sugar.
If cord and medulla are intact, TONIC control is OK, but responses to
challenge are very deficient, and there is no anticipation or
coordination with somatic responses.
PONS:
 micturition centre (starts to function only well after birth).
CEREBELLUM:
 motion sickness - autonomic effects salivation, sweating
 Experimental stimuli in cerebellum cause changes in BP, heart rate
 Injury to the cerebellum often affects frequency of micturition.
HYPOTHALAMUS: Sherrington's "head ganglion" of the autonomic NS;
but without cerebral cortex, control is incomplete.
 ‘Centres’: heat/cold; homeostatic responses; resistance to stress;
organises visceromotor; rage reaction. (NB functional areas do
not necessarily correspond to nuclei.
In general stimulation of anterior hypothalamus gives parasympathetic
effects; posterior gives sympathetic effects.
AMYGDALA:
 stimuli cause changes in sympathetic and parasympathetic (BP);
 removal causes placidity (deficits in social ranking; submissivity).
CEREBRAL CORTEX:
 Lesions can affect micturition control; poor temperature regulation.
 Stimuli all over (esp frontal) affect BP control; shunting of blood,
anticipatory and response. Anticipatory vasodilation of arterioles in
muscles about to be active.
Cerebral localisation of autonomic activity reflects somatic in motor
and premotor; visceral afferents reach sensorimotor primary and sensory
cortex via NTS and VPM; interconnections to posterior orbito-frontal
cortex, mediodorsal (MD) thalamus and limbic structures
Complete control of ANS requires all parts of the CNS
----------------------------
ORGAN CONTROL BY SYMPATHETIC & PARASYMPATHETIC SYSTEMS
Pelvic
--------------------------RECEPTORS
Cholinergic
(N1 nicotinic
N2 nicotinic
M1, 3, 5 muscarinic
M2, 4 muscarinic
ion channel
ion channel
Gαq; PLC; IP3 & DAG
Gαi, o; AdCycl; cAMP
somatic NS)
symp., parasymp.ganglia; adrenal medulla
Adrenergic
α1 (NA>A)
α2 (NA>A)
β1 (A>NA)
β2 (A>NA)
β3 (A>NA)
Gαq; PLC; IP3 & DAG
Gαi; AdCycl; cAMP
Gαs; AdCycl; cAMP
Gαs; AdCycl; cAMP
Gαs; AdCycl; cAMP
predominate on blood vessels
predominate on presynaptic terminals
e.g. heart on SAN, muscle; JGA,
e.g. bronchial, coron art smooth muscle, liver
e.g. fat cells, vasodilate salivary gland
e.g. heart bradycardia; presyn muscle vasodil.
5-HT
ATP P2 purinoceptors Ca channel
NO e.g. use of TNG in angina, sildenafil (Viagra) in erectile dysfunction; in pulmonary oedema.
Peptides: VIP, opioid peptides, somatostatin; substance P, CGRP in visceral afferents
SUMMARY OF AUTONOMIC CONTROL OF END ORGANS
(Symp = sympathetic; PS = parasymp)
EYE
 Pupil size (Symp α1 dilates, PS (M) (III) constricts), (opiates constrict)
 Accommodation: ciliary muscle (PS (III) accommodates), pupil changes;
 Lacrimation (VII): via int. acoustic meatus and sphenopalatine ganglion
Afferent stimuli: light, accommodation. Consensual pupillary reflex.
Pupil constriction on stimulation of visual area 19 (the visual area giving the most
corticofugal fibres; role in fixation), and of frontal eye fields (area 8; connected to limbic
structures, hypothalamus, PAG)
Sympathetic cilio-spinal centre (C8,T1) > SCG > NA symp fibres to eye;
Horner's syndrome (symp denervation of head) - usually caused by lesion at the neck of the
first rib as sympathetic chain leaves the chest.
Parasympathetic from Edinger-Westphal III, via III > ciliary ganglion > ciliary nerves (ACh)
Maximum pupillary dilation probably needs both an increase in sympathetic and a decrease
in parasympathetic tone
Think about drugs applied to eye to dilate pupil in ophthalmology
Lacrimation - VII (long complex pathway: facial nerve parasympathetic (N & M) via
internal acoustic meatus, petrosal nerves, spheno-palatine ganglion, to gland). Basal,
reflex and psychic tears.
CARDIOVASCULAR
 Control of heart rate & force
 Control vessel tone (esp. arterioles);
 Control blood volume
Afferents: baroreceptors, chemoreceptors, via IX, X to nucleus of solitary tract;
all somatosensory especially pain
Hypothalamus posterior: stimulation gives pressor BP+, rate+, vasoconstrictor
Hypothalamus anterior: stimulation gives depressor, vasodilator; (osmoreceptor neurons for
control of body water)
Some hypothalamic effects are indirect via brain stem centres; some are direct
Cerebellum: stimulation anywhere leads to cardiovascular changes
Cerebral cortex: anticipatory vascular changes before movement; Stimulation motor areas 4,
6: vasomotor changes even in paralysed limbs
Sympathetic (β1):
increased speed SA node, speed AV conduction, positive inotropic;
vasoconstricts/dilates vascular beds depending on receptors.
Parasympathetic (M2): decreased speed SA node and conduction, (minor negative
inotropic); splanchnic dilation
THERMOREGULATION
 Control of vascular system
 Control of sweating (cholinergic sympathetic),
 Control of metabolism: via ANS; control thyroid
Spinal/ bulbospinal animals are poikilothermic; need HT for homeothermic regulation
Hypothalamus anterior: heat loss: thermosensitive neurons;: local heating or electrical
stimulation leads to panting, heat loss
Hypothalamus posterior: heat conservation: stimulation gives shivering, vasoconstriction,
piloarrection (no thermoreceptor neurons). Bilateral lesions post hypothalamus impair
capacity to adapt to low temperature. Symp stimulates brown fat metabolism (neonate)
Pyrogen responses: affect thermostats of anterior HT (via PGs - aspirin); responses
depend on integrity of posterior HT
If injected into anterior hypothalamus : pyrogens, 5HT raise body temp;
A, DA, NA lower body temperature.
Postoperative hyperthermia common after operations on/ HT, suprasellar pituitary tumours
Piloarrection is produced by stimuli in many areas (but NB temp, rage)
Shivering produced by a graded increase in  tone (10-20/sec contractions); suppressed in
cortical voluntary movement
Associated somatic behaviour: stamping feet when cold; “its too hot to move”; clothes
DIGESTIVE SYSTEM and FEEDING
 ANS influences all aspects; stimulated by parasympathetic activity.
 Motility and migrating myoelectric complex starting in duodenum.
 Secretion: control submandiular gland via VII, parotid gland via IX;
Gut: oesophagus to splenic flexure colon via X; hindgut pelvic PS. (ACh M).
Hypothalamus anterior: stimulation increases secretion/peristalsis (parasympathetic); senses
nutrients (glucose, FFA), body fat (leptin), GI & pancreatic hormones
Hypothalamus posterior: stimulation inhibits secretion and peristalsis (sympathetic)
Lesions in hypothalamus can result in gastric ulcers, haemorrhage; gastric bleeding is
common after intracranial operations.
Higher centres: gastric erosions appear rapidly in very nervous animals. Relationship
human peptic ulcers and “stress”
GI tract & enteric NS: (Hirschprung's disease - defect in submucosal (Auerbach's) plexus;
Crohn’s disease VIP increased
Enteric NS: 107-8 neurons; control peristalsis & secretion so gut is relatively independent of
CNS; trophic effects
Feeding and drinking - see separate lecture
URINARY TRACT
Kidney
 Control (reduce) renal blood flow (sympathetic; α1)
 Control (increase) renin secretion via JGA (sympathetic; β1 )
Bladder: Afferents signal distension to sacral cord via pelvic plexus
Efferents - pelvic parasympathetics (ACh; M2)) stimulates micturition
sympathetic?; int sphincter? – poorly understood. (NB somatic to external sphincter)
Bladder centre in sacral cord - automatic bladder in spinal animals. After spinal injury
humans can learn a somatic reflex to empty bladder.
Pontine inhibitory centre: develops postnatally with bladder control.
GENITAL TRACT
Erection - parasympathetic vasodilation; role ACh M3; NO cGMP, Viagra; VIP
Emission - sympathetic - slow contraction vas, seminal vesicle smooth muscle;
Ejaculation - somatic (pudendal nerve. - rapid contraction of bulbospongiosus)
SLEEP
There are probably are no specific sleep centres in the HT but:
Hypothalamus: posterior lesions cause hypersomnia by preventing arousal; anterior lesions
cause insomnia. Role of orexins in arousal; narcolepsy.
Low frequency stimulation anteriorly can induce sleep; high frequency stimulation
causesawakening;
Lateral preoptic area lesions cause hyperactivity man & rats
Dorsal hypothalamic area stimulation causes sleep and motor preparation for sleep
Raphé: destruction causes insomnia; 5-HT from raphé promotes sleep.
EMOTIONAL & BEHAVIOURAL RESPONSES
Emotion is a feeling; other people can only observe the physical results
The appearance of emotional reactions can be elicited in decorticate animals.
"Sham rage" can be induced when only the hypothalamus is connected to the brain stem.
Any stimulus then causes sympathetic arousal which ceases immediately the stimulus
ends (cf real rage). Sham rage is abolished by a lesion of the posterior hypothalamus.
The autonomic system is central to the control of many systems. Hence it appears in various places in the syllabus
8.3.3 Autonomic innervations of bronchi; 8.7.2 Asthma and its pharmacology; 8.8.2 Short-term reflex control of ABP;
8.8.6.3 Sympathetic control; 8.8.8 cardiovascular regulation in critical illness; 8.9.3 Physiological changes during exercise;
16.5.2 Orbit and eyeinternal muscles of eye; 21.7 Pupillary reflexes; 22 Cranial nerves; 23.2 Hypothalamus; 24.2 Sleep;
51.1 Functions of hypothalamus; 51.2 Physiological response to stress; 52.1 body temperature regulation; 53.2 Effects of
general anaesthetics; 24.2 sleep ... and many others