Neuroendocrinology and autonomic functions Flashcards
(141 cards)
1
Q
What functions is the hypothalamus involved in the control?
A
sleep–wakefulness, thermoregulation, feeding, metabolic energy expenditure, drinking and fluid homeostasis, growth and reproduction.
2
Q
What is the structure of the hypothalamus?
A
consists of many nuclei clustered around the third ventricle. At its anterior end the floor of the ventricle thickens to become the median eminence which projects as the infundibulum (part of the pituitary stalk) to the posterior pituitary gland. The hypothalamus is divided into three longitudinal zones—the innermost of which, the periventricular zone, surrounds the third ventricle—and four subdivisions along its rostro-caudal axis.
3
Q
What input does the hypothalamus get from the hippocampus?
A
● By way of the subiculum, part of the hippocampal formation, which projects via the fornix to the mammillary bodies
●By way of the septum, also via the fornix, to connect with all three zones of the hypothalamus
4
Q
How does the hypothalamus get input from the amygdala?
A
via the stria terminalis, a loop that follows a similar course to the fornix, and the amygdalofugal pathway.
5
Q
What is the pathway of hypothalamic output via mammillary bodies?
A
via the mammillothalamic tract goes to the anterior thalamic nuclei (ATN) that are connected to the cingulate cortex. The cingulate cortex projects back to the hippocampal formation, so closing a loop (hypothalamus–ATN–CC–hippocampus–hypothalamus) termed the Papez circuit.
6
Q
What larger network is the papez circuit a part of?
A
includes the septum, amygdala, and prefrontal cortex which is concerned with emotion and memory.
7
Q
What connections of the mammillary bodies are implicated in memory?
A
It’s reciprocal connections via the mammillotegmental tract with the ventral tegmental nuclei in the midbrain
8
Q
The medial forebrain bundle passes through the lateral hypothalamic zone. What does it consist of?
A
monoaminergic axons ascending from brainstem nuclei. Many noradrenergic and serotonergic, but not dopaminergic, axons synapse with hypothalamic neurons.
9
Q
What input to the hypothalamus is important for hypothalamic control of the ANS?
A
The paraventricular hypothalamus and the lateral hypothalamic area receive visceral sensory input from the nucleus of the solitary tract (NST)
10
Q
The pituitary gland is divided into the neurohypophysis and the adenohypophysis. What is the structure of the neurohypophysis?
A
It is a direct outgrowth of the hypothalamus, consists of the posterior lobe, the median eminence, and the infundibulum.
11
Q
What is the structure of the adenohypophysis?
A
consists of the anterior lobe, an intermediate lobe (poorly developed in humans), and the pars tuberalis (an extension surrounding the infundibulum). The pars tuberalis and the infundibulum together make up the pituitary stalk
12
Q
What are the two groups of peptide-secreting neuroendocrine cells in the para ventricular nuclei of the HT?
A
Magnocellular and parvocellular cells
13
Q
Where do magnocellular cells send axons?
A
through the median eminence down the infundibular stalk into the posterior lobe as the tuberohypophyseal tract.
14
Q
Where are hormones made and released from magnocellular cells?
A
made in the cell bodies of the magnocellular cells and transported down their axons for release in the posterior lobe.
15
Q
What do parvocellular cells terminate on?
A
They have short axons which terminate on capillaries in the median eminence. These capillaries drain into long portal vessels that descend to form venous sinusoids in the anterior lobe; this vascular bed is the portal system.
16
Q
What happens to hormones secreted by parvocellular cells?
A
Hormones secreted by the parvocellular neurons into the median eminence are carried via the hypothalamic-pituitary portal circulation to the anterior lobe.
17
Q
How are homones delivered to the body from the pituitary gland?
A
Both lobes have fenestrated capillaries that lie on the blood side of the blood–brain barrier that drain into the systemic circulation
18
Q
What hormones do magnocellular cells in the supraoptic (SON) and paraventricular (PVN) nuclei secrete?
A
the nonapeptides arginine vasopressin and oxytocin.
19
Q
What is AVP, also known as antidiuretic hormone (ADH) secreted in response to?
A
an increase in extracellular fluid osmolality or reduced blood volume.
20
Q
What is the effect of ADH?
A
increases the water permeability of nephron collecting ducts, thereby promoting water reabsorption. This reduces extracellular fluid osmolality and urine output (an antidiuretic effect) so restoring blood volume. Thus, AVP acts as a negative feedback regulator, defending set points in body fluid osmolality and blood volume.
21
Q
Where are the osmoreceptors which respond to changes in osmolality?
A
vascular organ of the lamina terminalis (OVLT), one of the
circumventricular organs of the brain which lie on the blood side of the blood–brain
barrier. Osmolality-sensitive neurons in the OVLT synapse with the PVN and SON cells and increase their firing rate as osmolality rises.
22
Q
hypovolemia greater than 10% stimulates AVP secretion, what is the role of baroceptors in this?
A
Hypovolemia lowers mean arterial blood pressure. This is detected by stretch recep-
tors (baroreceptors) in the walls of the carotid sinus and aorta. The afferents of these pressure sensors run in the glossopharyngeal (IX) and vagus (X) cranial nerves to the nucleus of the solitary tract (NST) in the medulla. The NST activates noradrenergic neurons in the ventrolateral medulla which project to the PVN and SON to bring about AVP release. A reduced blood pressure causes decreased firing of the baroreceptor afferents and hence disinhibition of the circuitry triggering AVP secretion.
23
Q
What is renin secreted by?
A
the juxtaglomerular apparatus (JGA) of the kidney in response to several factors contingent on a fall in blood volume.
24
Q
What is renin and what is its function?
A
Renin is a proteolytic enzyme which cleaves a plasma protein, angiotensinogen, to yield a decapeptide, angiotensin I. This is further cleaved by angiotensin converting enzyme (ACE), expressed on pulmonary endothelial cells, to the octapeptide, angiotensin II
25
What are the effects of angiotensin II?
Angiotensin II stimulates the subfornical organ (a circumventricular organ), neurons of which stimulate AVP secretion. In addition, AII stimulates drinking, vasoconstriction, and
the secretion of aldosterone; all actions which help restore blood volume and pressure.
26
what aspects of reproductive function is oxytocin implicated in ?
Its stimulation of smooth muscle contraction underlies the milk ejection reflex in lactating females, and
maintenance of uterine contractions during parturition
27
Suckling is the most potent stimulation for milk ejection, What is the pathway of this reflex?
Primary afferents from the areolar and nipple skin relay with spinothalamic tract neurons in the dorsal horn of the spinal cord. Spinothalamic input causes oxytocin secretion via an undefined neural pathway
from midbrain to the PVN and SON.
28
How does the uterine smooth muscle become sensitive to oxytocin at term?
a rise in maternal estradiol/ progesterone ratio upregulates oxytocin receptors in uterine smooth muscle
29
What evokes the secretion of oxytocin during labour?
pressure of the fetal head on the cervix, via a reflex pathway similar to that for milk ejection.
30
What is the effect of oxytocin during birth?
oxytocin stimulates contractions of the uterine smooth muscle, further increasing the pressure of the fetus on the cervix.
This positive feedback mechanism is the Ferguson reflex.
31
What social interactions does oxytocin facilitate?
● Pair bonding—the tendency of two individuals in a sexual relationship to stay together—in both sexes
● Triggering maternal behavior
● Trust between individuals
32
What mediates the social interactions facilitated by oxytocin?
mediated by projections of hypothalamic oxytocin
neurons to limbic structures involved in emotion, and to the ventral tegmental area
(VTA) of the dopaminergic reward system.
33
What mechanism underlies pair bonding?
Oxytocin neurons fire during sexual intercourse in both women and men, and oxytocin produces feelings of pleasure and increased libido.It is postulated that oxytocin release becomes
conditioned by repeated intercourse with the same partner. In this model sexual/romantic love is seen as an addiction to a specific individual organized by oxytocin.
34
What is the mechanism of oxytocin triggering maternal behaviour?
rats involves increased oxytocin signaling to the VTA and consequently increased dopamine release from the nucleus accumbens.
35
How does oxytocin facilitate trust?
oxytocin could operate by
suppressing fear circuitry of the amygdala and brainstem.
36
What is the mechanism of the feelings of love and empathy felt by individuals dosed with 3,4-methylenedioxy-
methamphetamine?
could be because MDMA stimulates oxytocin secretion by activation of 5-HT1A serotonin receptors.
37
How does acute stress inhibit oxytocin release?
via actions of noradrenaline (norepinephrine) and
adrenaline (epinephrine).
38
What are the two types of hypophysiotropic hormones?
those that excite secretion are termed releasing hormones, those that inhibit are called release-inhibiting hormones.
39
Secretion from the neuroendocrine axes is modulated by negative feedback, what is this?
defined as a mechanism that acts to hold some variable at a set point. In endocrinology the set point is generally the blood concentration of a hormone and the negative feedback operates at several levels of the neuroendocrine axis.
40
What occurs in the neuroendocrine axis when the concentration of the end product hormone exceeds the set point?
more receptors are activated in the hypothalamus and anterior pituitary which consequently reduce their output of hormones. The effect is that, after some delay, the concentration of end product hormone falls
41
What happens in the neuroendocrine axis when the concentration of the hormone falls below the set point?
the hypothalamus and pituitary secrete more of their hypophysiotropic and trophic hormones, provoking an increase in concentration of the end product hormone.
42
What is autofeedback inhibition?
special case of negative feedback in which a substance directly inhibits its own synthesis
43
What is the pattern of secretion of hypothalamic hormones?
pulsatile with a period of 60–180 min. This drives pulsatile release of anterior pituitary hormones. The amplitude and period of the pulses varies on a circadian (about a day) basis and in some instances on longer time scales.
44
What is the function of the HPA axis?
regulates the synthesis and secretion of glucocorticoids, a group of steroid hormones which influence energy substrate metabolism. Most NB- cortisol
45
In the HPA axis what do cells in the paraventricular nucleus of the hypothalamus secrete?
corticotrophin releasing hormone (CRH), a peptide which acts synergistically with arginine vasopressin to stimulate release of adrenocorticotrophic hormone (ACTH) from corticotrophs
46
What is ACTH cleaved from?
large precursor, pro-opiomelanocortin.
47
Where does negative feedback of cortisol operate?
at the hippocampus, hypothalamus and pituitary
48
Where is the brain biological clock that drives the circadian rhythm?
Suprachiasmatic nucleus
49
How is ACTH/ cortisol secretion affected by the circadian rhythm?
ACTH pulses are greatest early in the morning and decline through the day to reach a low point around midnight. Cortisol secretion follows a similar pattern. This daily rhythm is influenced by the timing of light and dark, sleep and meals.
50
Which two receptors mediate the effects of cortisol?
mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These are members of a nuclear receptor superfamily that includes receptors for other steroids and for thyroid hormones.
51
When cortisol receptors are unbound, where are they situated?
present in the cytoplasm, complexed with heat shock proteins, molecular chaperones that stabilize the receptors into their functional configuration.
52
What is the effect of glucocorticoids/ cortisol on the receptor?
Glucocorticoids such as cortisol diffuse readily across cell membranes. Binding of cortisol causes the receptor to translocate into the nucleus where it binds to specific sequences of DNA, hormone responsive elements, thereby increasing or decreasing the transcription of specific genes
53
What is the distribution of mineralcorticoid and glucocorticoid receptors?
Mineralocorticoid receptors are in greatest numbers in limbic structures. Glucocorticoid receptors are more widespread, and expressed in glia as well as neurons. corticotrophs of the anterior pituitary, CRH- secreting neurons of the hypothalamus, and hippocampal neurons express GRs
54
Why does cortisol affect different target tissues depending on its concentration?
MRs have a high cortisol affinity they are mostly occupied at basal concentrations of the steroid. By contrast, GRs have a low affinity so are only occupied when the cortisol concentration is high, such as early morning.
55
The hypothalamic–pituitary–adrenal axis is activated in stress. What is the definition of stress?
generally it is a state seen in situations that derange homeostasis, or in which there is actual or perceived harm, loss, or challenge. Stressors, agents that cause stress, can be physiological or psychosocial, often arising in situations over which an individual has little control. An operational definition of stress is any state in which there is a large and/or prolonged rise in ACTH and glucocorticoid concentrations.
56
Why is cortisol useful in acute stress?
overall effect is to harness long-term energy substrates and convert them to readily available substrates, glycogen and glucose. In addition, cortisol potentiates the effects of catecholamines.
57
What inputs on on the CRH-secreting cells of the paraventricular nucleus activate the HPA axis in stress?
● Stress-evoked arousal activates noradrenergic neurons in the locus coeruleus which project to the PVN.
● Visceral sensations associated with thirst and hunger are transmitted via the glossopharyngeal (IX) and vagus (X) nerves to the nucleus of the solitary tract and adjacent regions of the medulla. These structures project catecholaminergic axons to activate the PVN.
● Inputs from the circumventricular organs which monitor osmolality or release arginine vasopressin go to the PVN to activate the HPA during dehydration.
● Neurons in the midbrain and pons, many cholinergic, project to the PVN and are thought to transmit visual, auditory, and somatosensory input associated with stressful situations.
●MosthypothalamicnucleiprojecttothePVNandtheseconnectionsfunnelinforma- tion about stressful situations from prefrontal cortex and limbic structures such as the amygdala or hippocampus.
58
What are the deleterious effects of protracted activation of the HPA during chronic stress?
High concentrations of glucocorticoids acting via GRs can impair hippocampal function and can even kill hippocampal cells. More generally, chronic activation of the HPA axis usually depresses the immune system.
59
What is an example of how the immune system effects the nervous system?
the cytokine interleukin-1, released by immune system cells in response to infection, stimulates the OVLT to secrete prostaglandin E2. This enhances CRH release by the PVN. The study of the reciprocal interactions between nervous and immune systems is psychoneuroimmunology.
60
How does the tripeptide Thyrotrophin releasing hormone (TRH) reach the ant pituitary to stimulate thyrotrophs to secrete TSH?
synthesized in PVN neurons. TRH secreted by axon terminals of these cells in the median eminence is carried by the hypothalamic–pituitary portal system to the anterior pituitary
61
What is the structure of TSH?
is a glycoprotein consisting of two chains, a and b.
62
What is the effect of TSH?
It is liberated into the systemic circulation and stimulates division and growth of cells in the thyroid gland, and the synthesis and secretion of the thyroid hormones. There are two thyroid hormones, thyroxine (T4) and triidothyronine (T3), named for the number of iodine atoms they contain
63
What is the structure of thyroid hormone receptors?
members of the steroid receptor superfamily. They form heterodimers with retinoid X receptors.
64
How do thyroid hormone receptors differ from glucocorticoid receptors?
the heterodimer binds to hormone-responsive elements in the DNA in the absence of ligand.
65
Thyroid receptors have a higher affinity for T3 than T4, how is T4 converted to T3?
T4, which forms the bulk of the secreted hormones, is a prohormone which is converted to T3 by the neuronal cytosolic enzyme, 5¢-deiodinase II.
66
How is thyroid hormone output controlled by negative feedback at several levels of the HPT axis?
A drop in thyroid hormone concentration causes the increased secretion of TSH by thyrotrophs of the anterior pituitary. TRH secretion from the hypothalamus is also subject to feedback inhibition by both T4 and T3.
67
Pulses of TRH secretion drives pulsatile TSH output. How do these changes throughout the day?
frequency and amplitude of the pulses is entrained into a circadian rhythm by the suprachiasmatic nucleus, rising throughout the night, falling during the morning, and remaining low throughout the afternoon. This circadian rhythm is sensitive to light and dark, but unaffected by sleep patterns.
68
How is thyroid secretion increased with cold exposure?
Temperature-sensitive neurons in the preoptic hypothalamus which get input from skin thermoreceptors project to brainstem noradrenergic neurons. These, in turn, synapse with the TRH-secreting cells of the PVN. Cold exposure activates the noradrenergic neurons, provoking a rise in TRH secretion within a few minutes. The resulting increase in the concentrations of thyroid hormones enhances metabolic rate, helping to maintain core temperature
69
What is the function of growth hormone?
stimulates cell division and growth of many tissues, particularly during the perinatal period and the growth spurt that heralds puberty, enhancing protein synthesis by increasing transcription and translation. GH mobilizes fatty acids as energy substrates. This is adaptive during exercise, stress, and fasting, three major physiological variables which increase GH secretion.
70
GH secretion from somatotrophs of the anterior pituitary is regulated by which two peptide hormones?
growth hormone releasing hormone (GHRH) and somatostatin.
71
Where is growth hormone releasing hormone synthesized?
arcuate nucleus of the hypothalamus.
72
where are somatostatin-containing cells responsible for inhibiting GH secretion restricted to?
hypothalamic periventricular nucleus.
73
What are the respective effects of GHRH and somatostatin on GH secretion, and how do they exert these?
exert their opposing effects on GH secretion via GPCRs linked to the cAMP second messenger system; GHRH receptors enhance, while
somatostatin receptors reduce, cAMP.
74
What is the pattern of secretion of GH?
The secretion of GH is circadian and pulsatile, driven mostly by pulses of GHRH from the hypothalamus. The pulses are much bigger at night and triggered by deep slow wave sleep. This nocturnal GH secretion is greatest in children and declines with age.
75
What brings about GH secretion?
brought about by a serotonergic pathway from the brainstem to the hypothalamus.
GHRH secretion is also stimulated by dopaminergic, noradrenergic, and enkephalinergic pathways in the brain. Thyroid hormones are required for normal levels of GH synthesis and secretion.
76
How does Negative feedback control of GH secretion occur?
occurs at the pituitary by suppression of the synthesis and secretion of GH, and at the hypothalamus by reduction of GHRH secretion. GH also stimulates the secretion of somatostatin. This negative feedback is exerted by insulin-like growth factor (IGF-1), one of a group of peptides called somatomedins which mediate the effects of GH. IGF-1 is produced either in the brain, or peripherally, in
response to GH.
77
What stimulates GH secretion during puberty/ the growth spurt?
gonadal secretion of androgens and estrogens
rises,
78
neurons scattered throughout the hypothalamus synthesize a decapeptide,gonadotrophin- releasing hormone. What is the effect of GnRH?
GnRH is secreted from axon terminals in the median eminence into the portal system. GnRH stimulates gonadotrophs of the anterior pituitary to secrete two gonadotrophins, follicle stimulating hormone (FSH) and luteinizing hormone (LH)
79
What is the structure of gonadotrophins?
large glycoproteins each consisting of two peptides, an a chain and a b chain. The a chains of FSH and LH are identical (and very similar to the a chain of TSH) but the b chains are distinct.
80
What is the effect of gonadotrophins?
stimulate the gonads to produce sex steroids and have effects on gamete development.
81
What is the pattern of secretion of gonadotrophins?
secretion is cyclical in females but not in males. The secretion of gonadotrophins is pulsatile, as with other anterior lobe hormones, and is driven by bursts of GnRH from the hypothalamus. GnRH neurons have an intrinsic rhythmicity but this is modified by steroid hormones. In men, the pulses are regular, spaced about 3 hours apart, but in women the period varies between 1 and 12 hours depending on the phase of her reproductive cycle. Humans have a circadian rhythm in testosterone secretion and women have modest cyclical changes in blood testosterone concentration, higher around ovulation
82
What is the effect of LH at the testis?
stimulates Leydig cells to synthesize and secrete androgens, principally testosterone.
83
What is the effect of FSH at the testis?
FSH, together with testosterone, acts on Sertoli cells to organize the development of spermatozoa and secrete a glycoprotein, inhibin
84
What is the mechanism of negative feedback control of gonadotropins in males?
Testosterone acts both at the hypothalamus, decreasing the frequency of the episodic GnRH bursts, and at the anterior pituitary, making it less responsive to GnRH. Inhibin specifically suppresses only FSH secretion and acts only at the anterior lobe.
85
What is the role of the HPG axis in women?
● Stimulate the growth of a group of ovarian follicles (one of which goes to maturity)
● Produce cyclical changes in sex steroid output,which prepares the reproductive tract for fertilization and implantation
● Trigger ovulation at the appropriate time
86
What are the two phases of the female reproductive cycle?
The first half of the cycle (in women this is typically 1–14 days) is the follicular phase, because it is dominated by the growth of the ovarian follicle which secretes estradiol and inhibin. The second half of the cycle is the luteal phase (15–28 days), because after ovulation the follicle becomes a corpus luteum which secretes progesterone.
87
What is the negative feedback control of gonadotrophin secretion in females?
Feedback depends on the phase of the cycle. For most of the follicular phase low or moderate levels of estradiol, and inhibin, exert negative feedback effect on gonadotrophin secretion. However, by about day 14, levels of estradiol become high enough to flip the HPG axis into a positive feedback mode. Now the estrogen stimulates a rise in LH and FSH secretion, which triggers ovulation, and switches the steroid metabolism of the post-ovulatory follicle to produce progesterone. The rise in progesterone secretion at the start of the luteal phase terminates the positive feedback LH surge and the system reverts to negative feedback mode.
88
Which two levels does steroid feedback work at?
One is by changing the sensitivity of the anterior pituitary to GnRH. The other is by altering the size of the GnRH signal from the hypothalamus
89
How do steroids exert their effects on GnRH neurons (they do not have steroid receptors)?
steroids must exert their effects on these cells via neuronal afferents.
90
Progesterone reduces GnRH pulse frequency, how does this effect gonadotrophin release?
low frequency favors FSH release, high frequency LH release.
91
What is the effect of low estradiol levels on GnRH?
At low estradiol concentrations the GnRH pulse frequency and amplitude are such that the numbers of functional GnRH receptors on the gonadotrophs are relatively low. Consequently the anterior pituitary is moderately insensitive to GnRH. This is negative feedback in the follicular phase, and the low GnRH pulse frequency favors FSH release. Estradiol may affect GnRH pulse amplitude by acting on dopaminergic neurons that make presynaptic synapses on GnRH terminals
92
What is the effect of high estradiol levels in the late follicular phase on GnRH?
possibly acting via GABAergic neurons in the mediobasal hypothalamus, causes GnRH release to occur in high- frequency low-amplitude pulses. This pattern allows upregulation of GnRH receptors on the anterior pituitary gonadotrophs which become exquisitely sensitive to the GnRH. Consequently there is a rapid rise in LH. This is positive feedback.
93
The pre-ovulatory surge in LH is augmented by GnRH self-priming. What is this?
refers to an increase in gonadotrophin release seen with repeated pulses of GnRH. It depends on early induction of (unknown) genes by GnRH and/or progesterone.
94
What is the effect of rising progesterone on GnRH?
rising progesterone concentrations switch the secretion of GnRH into a low-frequency high-amplitude pattern of release. This downregulates GnRH receptors in the anterior pituitary so that gonadotrophin secretion plummets in the luteal phase. Progesterone may exert its effects via b-endorphin neurons.
95
What is the cause of the inactivity of the HPG axis until puberty?
This is due to a neural brake in the CNS and not because of the lack of gonadal steroids. The nature of this neural brake is unclear, but GABA and neuropeptide Y and kisspeptin have all been implicated.
96
What is the trigger for puberty?
The precise trigger for puberty is not known, but it involves a metabolic signal that encodes body mass. In girls, a critical mass of 30 kg appears necessary for puberty to commence, with menarche (time of first menstrual period) occurring at about 47 kg. One candidate for the metabolic signal is leptin which is released by fat cells. The blood concentration of leptin is thought to signal the size of fat stores to the hypothalamus. Leptin inhibits neuropeptide-Y-containing neurons in the arcuate nucleus.
97
What is prolactin secreted by?
Lactotrophs of the anterior lobe
98
What is the structure of prolactin?
PRL is a glycoprotein with a similar amino acid sequence to growth hormone.
99
What is the function of prolactin?
It is one of several hormones that stimulates the growth of the mammary glands during pregnancy. Suckling produces a reflex secretion of prolactin which stimulates the synthesis and secretion of milk.
100
When is prolactin released?
PRL concentrations are highest during pregnancy and lactation. Like growth hormone, exercise and stress stimulate prolactin release.
101
How is prolactin synthesis and secretion inhibited?
by dopamine released into the portal system by dopaminergic neurons in the arcuate nucleus. Lactotrophs of the anterior pituitary express D2 dopamine receptors. These are GPCRs at which dopamine produces a fall in cAMP concentration, thereby reducing transcription of the prolactin gene
102
How is PRL released stimulated physiologically?
● Vasoactive intestinal peptide(VIP)secreted
by hypothalamic neurons into the portal system. This is the main short-term PRL releasing factor.
● Estrogens(producing a mid-cycle peak in PRL secretion) important in late pregnancy.
●Oxytocin from the posterior pituitary, which gains access to the anterior lobe via tiny blood vessels called the short portal vessels. This is important in lactating women.
103
Why are lactating women infertile?
With frequent suckling (every 2–3 hours) the amount of prolactin released is sufficient to block ovulation by suppressing LH and GnRH secretion
104
What is the overall function of the autonomic/ visceral nervous system?
adjusts the contraction of smooth muscle and heart muscle and controls glandular secretion so that key physiological variables (e.g., core temperature, cardiac output, blood pressure, blood glucose) are maintained at levels appropriate to the environment or ongoing activities. The ANS is concerned with feedback regulation of physiological variables.
105
What are reflex activities in the ANS controlled by?
By definition there are no afferents in the ANS but, its reflex activities are controlled by somatic and visceral afferent input.
106
Many autonomic adjustments, though not negative feedback, are homeostatic in that they change physiological variables so as to cope with altered demands, what happens in response to stressors?
activation of the sympathetic nervous system (SNS) to targets such as the heart, blood vessels, airways, and liver results in increased cardiac output, regional alterations in blood flow, raised airflow through the lungs, and elevations in blood glucose concentrations, all adaptations which improve the chances of surviving the stress unscathed.
107
What does the ANS do in 'rest and digest' mode?
parasympathetic nervous system (PNS) activation is seen; the PNS generally stimulates exocrine gland secretion and promotes anabolic processes.
108
What is an example of a situation where the ANS works by positive feedback?
Sexual responses in humans
require autonomic reflexes (both sympathetic and parasympathetic) in which the motor response (enlargement of the penis or clitoris by vasocongestion) increases the firing of the same visceral afferents which drive the reflex response. This is positive feedback
because it carries the system away from its usual stable state.
109
Acetylcholine (ACh) is the major neurotransmitter at all autonomic ganglia. Was is its effect at each of its receptors?
ACh released from preganglionic neurons acts on nicotinic cholinergic receptors to produce a fast excitatory postsynaptic potential (epsp) which, if sufficiently large, makes the postganglionic cell fire. In addition ACh acts on M1 muscarinic receptors producing a slow epsp—prolonging the firing of the postganglionic cell by many seconds—by closing a population of potassium (KM) channels. In this way long-lasting autonomic responses are generated by brief stimuli.
110
Almost all terminals of the sympathetic postganglionic axons secrete noradrenaline, what is the only exception?
the cholinergic sympathetic supply to sweat glands.
111
What is the role of the adrenal glands in the ANS?
The adrenal medulla chromaffin cells are regarded as a postganglionic component of the SNS and secrete adrenaline (epinephrine; and noradrenaline, norepinephrine) directly into the blood as a result of activity in the preganglionic sympathetic fibers which supply it.
112
Autonomic nerve terminals, in addition to secreting noradrenaline or ACh, also release ATP and peptides as co-transmitters. What is the effect of ATP co-release?
acts on the smooth muscle of blood vessels to produce fast excitatory postsynaptic potentials and rapid contraction. This is followed by a slower response due to noradrenaline
113
Peptide co-transmitters in the ANS include neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). What is the function of these?
They prolong and modulate the effects of the primary transmitter. For example, NPY in sympathetic terminals enhances the vasoconstrictor response to noradrenaline. VIP from parasympathetic terminals on salivary glands
causes vasodilation which enables ACh to produce a greater salivary secretion.
114
core temperature of around 37∞C is maintained by behavioral and physiological mechanisms. What is the core?
defined as the inside of the head, trunk, and limbs, from deep to the subcutaneous fat layer.
115
When are physiological heat loss or heat gain mechanisms activated?
whenever the ambient temperature moves outside the thermoneutral zone, a window about 1∞C wide in which an individual feels comfortable. The thermoneutral zone depends on humidity, wind velocity, and clothing. For naked humans in still air at 50% relative humidity it is 28∞C.
116
What is the first response to ambient temperature moving outside the thermoneutral zone?
adjustment in firing of sympathetic nerves to smooth muscles of skin arterioles. In heat stress, firing is reduced and the fall in noradrenaline (norepinephrine) evoked vascular smooth muscle contraction causes cutaneous vasodilation. This warms the skin, increasing heat loss by radiation. In the cold, increased sympathetic activity causes cutaneous vasoconstriction.
117
What do larger excursions from the thermoneutral zone evoke?
either sweating or shivering.
118
How is sweating initiated?
Sweat glands are innervated by sympathetic neurons that are atypical in secreting acetylcholine. ACh acts on muscarinic receptors to trigger sweat production which causes skin cooling by evaporation.
119
What is shivering?
Shivering is the almost
simultaneous contraction of agonist–antagonist muscle pairs. It starts in jaw muscles
and spreads to the trunk and proximal limb muscles.
120
How is shivering initiated?
Shivering is brought about by activation of brainstem reticular neurons that synapse with g-fusimotor neurons. The contraction of intrafusal fibers excites stretch reflexes. So, shivering is mediated peripherally by the somatic not the autonomic nervous system. Muscle contraction generates heat.
121
What is non-shivering thermogenesis?
caused by increased sympathetic activity to brown adipose tissue (BAT), mostly located in the neck and between the shoulder blades. Released
noradrenaline acts on b3 adrenoceptors to stimulate a rise in cAMP. This activates lipolysis, liberating free fatty acids which are metabolized by b-oxidation in BAT mitochondria, and at the same time uncoupling oxidative phosphorylation in the mitochondria, generating heat.
122
The pre-optic area (POA) of the hypothalamus has internal warm thermoreceptors that
monitor core temperature, and gets input from skin warm receptors, what is the output of the POA?
It projects to the periaqueductal gray
which then relays via the raphe nucleus to preganglionic sympathetic neurons in the intermediolateral column of the spinal cord. This is the route by which vasomotor tone is adjusted. In addition the POA stimulates the supraoptic nucleus to secrete antidiuretic hormone from the posterior pituitary. This helps conserve water.
123
What is the input and function of the paraventricular (PVN) and dorsomedial hypothalamic (DMH) nuclei?
They get input from skin cold receptors and stimulate brown fat and shivering.
124
How does the hypothalamus integrate thermoregulatory responses?
Warm sensitive neurons in the POA modulate both heat loss, via the vasomotor pathway, and the heat gain mechanisms by inhibiting the PVN and DMH. that thresholds for activating either sweating or shivering can change.
125
The core temperature maintained by thermoregulation is the set point. What is it provided by?
is provided by the activity of interneurons in the hypothalamus that are not temperature sensitive. These are regulated by catecholaminergic neurons in the pontine reticular formation, and the set point is not constant.
126
What is the circadian rhythm of the temperature set point?
it falls about 0.5∞C during sleep, and is increased by progesterone during the luteal phase of the menstrual cycle by about the same amount. Chronic exposure to hot or cold environments cause gradual long-term shifts (adaptation) of the set point.
127
How does the ANS help the short-term regulation of mean arterial pressure?
At rest the ANS operates to maintain a roughly constant MAP by negative feedback. Mean arterial pressure is the product of cardiac output (Q), the volume output of the left ventricle per minute, and the peripheral resistance (R), which is related to the radius of the arterioles. The ANS regulates cardiac output via both sympathetic and parasympathetic supply to the heart. Both are tonically active at rest and increases
(decreases) in cardiac output are achieved by raising (lowering) sympathetic activity and reducing (elevating) parasympathetic activity.
128
What variables of CO do the sympathetic and parasympathetic system affect?
sympathetic activity raises both force and rate, whereas parasympathetic activity lowers rate, but has little effect on force because few parasympathetic fibers innervate the ventricles.
129
How is peripheral blood vessel resistance controlled?
controlled solely by altering the tonic firing rates of sympathetic neurons going to vascular smooth muscle. Increased firing frequency causes vasoconstriction which raises peripheral resistance.
130
Where does the circuitry for the negative feedback regulation of MAP reside?
medulla
131
How are changes in MAP sensed?
Baroreceptors are stretch receptors located in the carotid sinus and the aortic arch that are sensitive to rapid alterations in MAP. Their afferents run in the glossopharyngeal (IX) and vagus (X) cranial nerves respectively and terminate in the nucleus of the solitary tract
132
How does the nucleus of the solitary tract control ANS outflow to the heart?
The NST projects to the dorsal vagal nucleus (DNX) and to the nucleus ambiguus (NA), both of which give rise to preganglionic parasympathetic axons
that run in the vagus nerve to the heart. The NTS controls sympathetic outflow to heart
and blood vessels by input to the caudal ventrolateral medulla (CVLM). This contains GABAergic inhibitory neurons which synapse in the rostral ventrolateral medulla, axons
of which run down the spinal cord, terminating on preganglionic sympathetic neurons.
133
A rise in MAP increases the firing rate of baroreceptor afferents, what is the ANS response to this?
this directly activates
the parasympathetic innervation to the heart, slowing its rate. However, the presence of inhibitory neurons in the CVLM means that baroreceptor discharge suppresses sympathetic outflow to the heart, reducing its rate and force of contraction, and arterioles,
which reduces peripheral resistance. The net effect is a fall in blood pressure back to the set point.
134
How are cardiovascular variables modified to match circumstances?`
During exercise the cerebellar and cerebral cortex act to modify hypothalamic autonomic regulation. Similarly cardiovascular responses seen in emotional states require limbic system components such as the amygdala and the cingulate cortex.
135
Which are the primary efferents in breathing?
Axons of motor neurons in spinal segments C3–C5 run in the phrenic nerves to the diaphragm, contraction of which increases chest volume during inspira-
tion. Motor neurons in C4–L3 supply neck muscles and external intercostal muscles that aid inspiration, and internal intercostal muscles and abdominal muscles responsible for expiration.
136
What is the dorsal respiratory group?
They are clusters of neurons in the nucleus of the solitary tract (NST) of the medulla. One cluster are inspiratory upper motor neurons which synapse with spinal motor neurons supplying the diaphragm and external intercostal muscles. These cells are active during quiet inspiration. They receive inputs from another cluster of DRG cellsthat integrate the
visceral inputs.
137
What are the ventral respiratory group (VRG)?
They are in the ventrolat-
eral medulla, are silent in quiet breathing but active in heavy breathing. The VRG houses both inspiratory and expiratory neurons which are reciprocally innervated by inhibitory connections. Hence, when the inspiratory neurons are firing the expiratory neurons are silent and vice versa.
138
What is the pontine respiratory group?
It includes the Kölliker–Fuse nucleus (KFN), which drives the medullary respiratory neurons so as to prolong inspiration (apneusis), and cells in the parabrachial nucleus (PBN) of the rostral pons which overrides apneusis, thereby terminating inspiration.
139
Where does the basic respiratory rhythm originate from?
from the pre-Botzinger complex (pBOT), a nucleus just rostral to the VRG which makes extensive connections with the VRG, DRG, and pons. Pre-Botzinger complex cells have intrinsic pacemaker properties.
140
Integrating neurons in the DRG receive sensory input, largely via the vagus nerve. What are these sources which modify the basic rhythm of breathing?
● Nociceptors (lung irritant receptors) which trigger the cough reflex.
● Pulmonary stretch receptors which inhibit inspiration.
● Baroreceptors, which inhibit inspiration: if blood pressure falls (as a result of hemorrhage, for example) depth of inspiration increases.
● Peripheral chemoreceptors in the carotid body and aortic arch which are activated by
large reductions in partial pressure of O2
● Central chemoreceptors which are excited by a rise in brain extracellular fluid concentrations of CO2 and fall in pH and drive deeper breathing in response.
141
Where are central chemoreceptors found?
in the retrotrapezoid nucleus which is adjacent to the nucleus of the facial (VII) nerve.
