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INTRODUCTION
THE SECRETORYHYPOTHALAMUS
AN OVERVIEW OFTHE HYPOTHALAMUS
Homeostosis
Structure of the Hypotholomus
ond Connections
PATHWAYS TO THE PITUITARY
Hypotholomic
Controlof the Posterior
Pituitory
Hypotholamic
Controlof the AnteriorPituitory
r Box 15.l OJ'Special
Inlerest:Stressand the Brain
CONCLUDING REMARKS
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482 C HAPTE R I 5 . C H E M I C A L C O N T R O L O F TBHMEI N A N D B E H A V I O R
V INTRODUCTION
It should be obvious by now that knowing the organization of synaptic
connections is essentialto understanding how the brain works. It's not
from a love of Greek and Latin that we belabor the neuroanatomyl Most
of the connectionswe have describedare preciseand specific.For exam-
ple, in order for you to read thesewords, there must be a very fine-grained
neural mapping of the light falling on your retina-how elsecould you see
the dot on this question mark? The information must be carried centrally
and preciselydispersedto many parts of the brain for processing,coordi-
nated with control of the motor neurons that closelyregulatethe six mus-
clesof each eye as it scansthe page.
In addition to anatomical precision, point-to-point communication in
the sensoryand motor systemsrequires mechanismsthat restrict synaptic
communicationto the cleft betweenthe axon terminal and its target.It just
wouldn't do for glutamate releasedin somatosensorycortex to activate
neurons in motor cortexl Furthermore,transmissionmust be brief enough
to allow rapid responsesto new sensoryinputs. Thus, at these synapses,
only minute quantitiesof neurotransmitterare releasedwith eachimpulse,
and thesemoleculesare then quickly destroyedenzymaticallyor taken up
by neighboring cells. The postsynapticactions at transmitter-gatedion
channelslast only as long as the transmitter is in the cleft, a few milliseconds
at most. Many axon terminalsalsopossesspresynaptic"autoreceptors"that
detectthe transmitter concentrationsin the cleft and inhibit releaseif they
get too high. Thesemechanismsensurethat this type of synaptictransmis-
sion is tightly constrained,in both spaceand time.
The elaboratemechanismsthat constrain point-to-point synaptictrans-
mission bring to mind a telecommunicationsanalogy.Telephonesystems
make possiblevery specificconnectionsbetween one place and another;
your mother in Tacomacan talk just to you in Providence,reminding you
that her birthday was last week. The telephone lines can act like precise
synapticconnections.The influenceof one neuron (your mother) is targeted
to a small number of other neurons (in this case,only you). The embar-
rassingmessageis limited to your earsonly. For a real neuron in one of the
sensoryor motor systemsdiscussedso far, its influence usually extendsto
the few dozen or few hundred cellsit synapseson-a conferencecall, to be
sure, but still relatively specific.
Now imagine your mother being interviewed on a television talk show,
which is broadcastvia a cable network. In this case,the widespreadcable
connectionsmay allow her to tell millions of people that you forgot her
birthday, and the loudspeaker in each television set will announce the
messageto anyone within earshot. Likewise, certain neurons communi-
cate with hundreds of thousandsof other cells.Thesewidespreadsystems
also tend to act relatively slowly, over secondsto minutes. Becauseof
their broad, protracted actions, such systemsin the brain can orchestrate
entire behaviors, ranging from falling asleep to falling in love. Indeed,
many of the behavioral dysfunctionscollectively known as mental disor-
ders are believed to result specificallyfrom imbalancesof certain of these
chemicals.
In this chapter,we take a look at three componentsof the nervous system
that operatein expandedspaceand time (Figure l5.I). One component is
L}resecretory hypothalamus. By secretingchemicalsdirectly into the blood-
stream, the secretoryhypothalamus can influence functions throughout
both the brain and the body. A secondcomponent, controlled neurally by
the hypothalamus, is the autonomicnervoussystem(,4NS),introduced in
Chapter 7. Through extensiveinterconnectionswithin the body, the ANS
V INTRODUCTION 483
-
o
(a)
: F
t
FIGURE I5.I
Patternsof communicationin the nervoussystem.(a) Mostof the systems we
havediscussed inthisbookmaybe described aspoint-to-point.The properfunctioningof
thesesystems requires restricted
synaptic
activationof targetcellsandsignalsof briefdura-
tion.In contrast,
threeothercomponents of the nervous system actovergreatdistances
andfor longperiods of time,(b) Neurons of thesecretory hypothalamus affecttheir
manytargetsby releasing hormones directlyintothe bloodstream. (c) Networlaof inter-
connected neurons of theANScanworktogether to activatetissuesalloverthe body.
(d) Diffusemodulatory systemsextendtheirreach withwidelydivergent axonal
proJectrons.
V THE SECRETORYHYPOTHALAMUS
Recallfrom Chapter 7 that the hypothalamus sits below the thalamus, along
the walls of the third ventricle. Ir is connecredby a stalk to the piruitary
gland, which danglesbelow the base of the brain, just above the roof of
your mouth (Figure 15.2). Although this tiny cluster of nuclei makes up
lessthan Io/oof.the brain'smass,the influenceof the hypothalamuson body
physiology is enormous. Let's take a brief tour of the hypothalamus and
then focus on some of the ways in which it exerts its powerful influence.
)
Periven-
1,,,"
tricular -,l
thalamus
Third
ventricle
FIGURE I5.3
Zonesof the hypothalamus. Thehypothalamus hasthreefunctionalzones:
lateral,
andperiventricular:The
medial, periventricular
zonereceivesinputsfromthe otherzones,the
brainstem,andthetelencephalon. cellsinthe periventricular
Neurosecretory zonesecrete
hormones intothebloodstream. cellscontrol
Otheroeriventricular theautonomicnervous
system.
FIGURE I5.4
lrlagnocellularncurprecl€tory cellr of thc lrypothelamur.Thisisa midsagittal view
of the hypothalamus andpituitaryMagnocellular
neurosecretory cellssecrete
oxytocinand
vasopressindirectlyintocapillaries
in the posterior
lobeof the pituitary
the delivery of the newbom. It also stimulates the ejection of milk from the
mammary glands. All lactating mothers know about the complex "let-
down" reflex that involves the oxytocin neurons of the hypothalamus.
Oxytocin releasemay be stimulated by the somatic sensationsgeneratedby
a suckling baby. But the sight or cry of a baby (even someone else,s)can
also trigger the release of milk beyond the mother's conscious control. In
each case,information about a sensory stimulus-somatic, visual, or audi-
tory-reaches the cerebralcortex via the usual route, the thalamus, and the
cortex ultimately stimulates the hypothalamus to trigger oxytocin release.
The cortex can also suppresshypothalamic functions, as when anxiety in-
hibits the letdown of milk.
Vasopressin, also called antidiuretic hormone (ADH), regulates
blood volume and salt concentration. When the body is deprived of water,
the blood volume decreasesand blood salt concentration increases.These
changes are detected by pressure receptors in the cardiovascular system
and salt concentration-sensitive cells in the hypothalamus, respectively.
vasopressin-containingneurons receive information about these changes
and respond by releasing vasopressin,which acts directly on the kidneys
and leads to water retention and reduced urine production.
Under conditions of lowered blood volume and pressure,communication
between the brain and the kidneys actually occurs in both directions (Fig-
ure 15.5).The kidneys secretean enzymeinto the blood calledrmin.Blevated
renin sets off a sequenceof biochemical reactions in the blood. Angiotensino-
gen, alarge protein releasedfrom the liver, is converted by renin to angiotensin
HYPOTHALAMUS
THE SECRETORY 487
Loweredblood
pressure
FIGURE I5.5
Communicationbetweenthe kidneysand the brain.Underconditions of lowered
bloodvolume or pressure,
the kidney Renininthe
reninintothe bloodstream,
secretes
bloodpromotes of the peptide
thesynthesis ll,whichexcites
angiotensin theneuronsin
organ.The
thesubfornical subfornicalneurons the hypothalamus,
stimulate an
causing
(ADH)oroduction
in vasooressin
increase anda feelins
of thirst,
an actual gland. The cells of the anterior lobe synthesizeand secretea wide
range of hormones that regulate secretionsfrom other glands throughout
the body (together constituting the endocrine system). The pituitary hor-
mones act on the gonads, the thyroid glands, the adrenal glands, and the
mammary glands (Table 15.1). For this reason, the anterior pituitary was
traditionally describedas the body's "master gland." But what controls the
master gland? The secretory hypothalamus does. The hypothalamusitself is
the true mastergland of the endocrinesystem.
The anterior lobe is under the control of neurons in the periventricular
area called parvocellular neurosecretory cells. These hypothalamic
neurons do not extend axons all the way into the anterior lobe; instead,
they communicate with their targers via the bloodstream (Figure 15.6).
These neurons secrete what are called hypophysiotropic hormones into
a uniquely specialized capillary bed at the floor of the third ventricle. These
tiny blood vesselsrun down the stalk of the pituitary and branch in the
anterior lobe. This network of blood vessels is called the hypothalamo-
pituitary portal circulation. Hypophysiotropic hormones secreted by
hypothalamic neurons into the portal circulation travel downstream until
they bind to specific receptors on the surface of pituitary cells. Activation
of these receptors causes the pituitary cells to either secrete or stop secret-
ing hormones into the general circulation.
Regulation of the adrenal glands illustrates how this system works. Located
just above the kidneys, the adrenal glands consist of two parts, a shell called
the adrenal cortex and a center called the adrenal medulla. The adrenal
cortex produces the steroid hormone cortisol; when it is released into the
bloodstream, cortisol acts throughout the body to mobilize energy reserves
and suppress the immune system, preparing us to carry on in the face of
life's various stresses.In fact, a good stimulus for cortisol release is stress,
ranging from physiological stress, such as a loss of blood; to positive emo-
tional stimulation, such as falling in love; to psychological stress, such as
anxiety over an upcoming exam.
Parvocellular neurosecretory cells that control the adrenal cortex determine
whether a stimulus is stressful or not (as defined by the release of cortisol).
These neurons lie in the periventricular hypothalamus and release a peptide
V THE SECRETORY
HYPOTHALAMUS 489
FIGURE I5.6
Parvocellularneunosecretory cellsof the hypothalamus. neurosecre-
Parvocellular
hypophysiotropic
torycellssecrete hormones intospecialized bedsof thehypothal-
capillary
portalcirculation.These
amo-pituitary hormones lobeof thepituitary,
travelto theanterior
wheretheytrigger of pituitary
the release
or inhibit hormones fromsecretorycells.
FIGURE I5.7
The stress resPonse.Underconditions of physiological,
emotional,or psychological
stimu-
lalionor stress,
the periventricular
hypothalamus secretescorticotropin-releasing
hormone
(CRH)intothe hypothalamo-pituitary portalcirculation.This
triggersthe release
of adreno-
corticotropichormone(ACTH)intothe generalcirculation. ACTH stimulates the releaseof
cortisolfromthe adrenalcortex.Cortisolcanact directlyon hypothalamic neurons,aswell
as on otherneuronselsewhere in the brain.
again: Your heart rate slows and blood pressure drops, digestive functions
work harder on breakfast, and you stop sweating.
Notice that you may not have moved out of your chair throughout this
unpleasant event. Maybe you didn't even move your pencil. But your
body's internal workings reacted dramatically. Unlike the somaticmotlr system,
whose alpha motor neurons can rapidly excite skeletal muscles with pin-
point accuracy,the actions of the ANS are typically multiple, widespread,
and relatively slow. Therefore, the ANS operates in expanded space and
time. In addition, unlike the somatic motor system, which can only excite
its peripheral targets, the ANS balances synaptic excitation and inhibition
to achieve widely coordinated and graded control.
ANS Circuits
Together,the somatic motor system and the ANS constitute the total neu-
ral output of the CNS. The somatic motor system has a single function: It
innervates and commands skeletal muscle fibers. The ANS has the complex
492 cHAprER | 5 . cHEMtcALcoNTRoLoFTHEBRAINANDBEHAVIoR
FIGUREI5.8
ANS
The organization ofthe three neural
outputs of the CNS. The sole output of
Somaticmotor Sympathetic Parasympathetic
the somatic motor system is the lower motor
neuronsin the ventral horn ofthe spinalcord
and the brain stem,which Sherrinetoncalled CNS
the finalcommon pathwayfor thJgeneration
of behavior:Br.rtsome behaviors,such as sali- Preganglionic
vating,sweating,and genitalstimulation,de- fibers
pend insteadon the ANS.Thesevisceralmo-
tor responsesdepend on the sympatheticand Autonomic
parasympathetic divisionsof the ANS, whose (sympathetic)
lower motor neurons(i.e.,postganglionic ganglion
neurons)lie outsidethe CNS in autonomic PNS
ganglra.
Autonomic
(parasympathetic)
ganglion
Postganglionic
fibers
FIGURE I5.9>
The chemicaland anatomicalorganizationof the sympatheticand parasym-
patheticdivisionsof the ANS. Noticethatthepreganglionic
inputs
of bothdivisions
useAChasa neurotransmitter:The
postganglionic
parasympathetic
innervation
of thevisceral
organs
alsousesACh,butthepostganglionicsympathetic
innervation
usesnorepinephrine
(with the exceptionof innervationof the sweat glandsand vascularsmooth musclewithin
skeletalmuscle,which use ACh).The adrenalmedullareceivespreganglionic sympatheticin-
nervation and secretesepinephrine into the bloodstream when activated.Note the pattern
of innervation by the sympatheticdivision:Targetorgans in the chest cavity are contacted by
postganglionic neuronsoriginatingin the sympatheticchain,and target organsin the abdomi-
nal cavity are contacted by postganglionicneurons originatingin the collateral ganglia.
W THEAUTONOMICNERVOUS
SYSTEM
Dilates Constricts
pupil pupil oculomolor^
: * : . .. . . - - n e r v e( l l l )
Constricts
bloodvessels
Relaxes
airways
Accelerates
heartbeat
glucose
Stimulates ,l
"".\ and
Production /
\ release (
/
l
, Vaousnerve(X)
Stimulates , l '
digestion
-'" "-* "-"1
,x-"*"'q:r'"
Stimulates /
secretionof 'lcreas ,l
epinephrine and /
-- -- -^" / Stimulates
;!."".*)- pancreas
norepinephrine
fromadrenal ./ to releaseinsulin
medulla. ,i anddigestive
A enzvmes
A I
;
t/ .i
-
r
--l .r*,*, - -'""tilates blood
vesselsin gut
Small
intestine
,,
\ /-r,^00",
,Y'---X.'
urinary Y
Relaxes urinary
Stimulates
Sympathetic bladder bladderto contract i
chain
NEneurons
The preganglionic neurons of the sympathetic division lie within the in-
termediolateral
gray matterof the spinal cord. They send their axons through
the ventral roots to synapseon neurons in the ganglia of the sympathetic
chain, which lies next to the spinal column, or within collateral ganglia
found within the abdominal cavity. The preganglionic parasympathetic
neurons, on the other hand, sit within a variety of brain stem nuclei and
the lower (sacral)spinal cord, and their axons travel within severalcranial
nervesas well as the nerves of the sacralspinal cord. The parasympathetic
preganglionicaxons travel much farther than the sympatheticaxons, be-
causethe parasympatheticganglia are typically located next to, on, or in
their targetorgans(seeFigures15.8and I5.9).
The ANS innervates three types of tissue: glands, smooth muscle, and
cardiacmuscle.Thus, almost every part of the body is a target of the ANS,
as shown in Figure 15.9. The ANS:
I Innervatesthe secretoryglands(salivary sweat,tear, and variousmucus-
producing glands).
r Innervates the heart and blood vesselsto control blood pressureand
flow
t Innervatesthe bronchi of the lungs to meet the oxygen demandsof the
body.
I Regulatesthe digestiveand metabolic functions of the liver, gastroin-
testinal tract, and pancreas.
t Regulatesthe functions of the kidney, urinary bladder, large intestine,
and rectum.
r Is essentialto the sexualresponses
of the genitalsand reproductiveorgans.
t Interactswith the body's immune system.
The physiological influences of the sympathetic and parasympathetic
divisionsgenerallyopposeeach other. The sympatheticdivision tends to be
most activeduring a crisis,real or perceived.The behaviorsrelatedto it are
summarizedin the puerile (but effective)mnemonic used by medical stu-
dents, calledthe four Fs: fight, flight, fright, and sex. The parasympathetic
division facilitatesvarious non-four-F processes, such as digestion,growth,
immune responses,and energy storage.In most cases,the activity levelsof
the two ANS divisionsare reciprocal;when one is high, the other tends to
be low and vice versa.The sympatheticdivision freneticallymobilizesthe
body for a short-term emergencyat the expenseof processesthat keep it
healthy over the long term. The parasympatheticdivision works calmly for
the long-term good. Both cannot be stimulatedstrongly at the sametime;
their generalgoalsare incompatible.Fortunately,neural circuitsin the cNS
inhibit activity in one division when the other is active.
some exampleswill help illustrate how the balance of activity in the
sympatheticand parasympatheticdivisions controls organ functions. The
pacemakerregion of the heart triggerseach heartbeatwithout the help of
neurons,but both divisionsof the ANS innervate it and modulate it; sym-
patheticactivity resultsin an increasein the rate of beating,while parasym-
pathetic activity slows it down. The smooth musclesof the gastrointestinal
tract are also dually innervated,but the effect of each division is the oppo-
site of its effecton the heart. Intestinal motility, and thus digestion,is stim-
ulated by parasympatheticaxons and inhibited by sympatheticaxons. Not
all tissuesreceiveinnervation from both divisions of the ANS. For exam-
ple, blood vesselsof the skin, and the sweat glands,are innervated only by
excitatory sympatheticaxons. Lacrimal (tear-producing)glandsare excited
only by parasympatheticinput.
1T THEAUTONOMICNERVOUS
SYSTEM 495
Blood
Axon
vessel
Small
intestine i t \
FIGURE I5.IO
The enteric division of the ANS. This cross-sectional view of the smai ntestrneshows
tne rrlente'ic plexusand t"e subnucousplex-s.
rhe two networ\s o{ tr^eente'ic divis'o^:
They both containvsceralsensoryand motor neuronsthat contro the functonsofthe
d gestrveorgans.
495 C HAPTE R I 5 . CHEMICALCONTROL
OFTHEBRATNAND
BEHAVIOR
V THE DIFFUSEMODULATORYSYSTEMS
OF THE BRAIN
Considerwhat happenswhen you fall asleep.The internal commands,,you
are becomingdrowsy" and "You are falling asleep"are messages that must
be receivedby broad regions of the brain. Dispensingthis information re-
quires neurons with a particularly widespreadpattern of axons.The brain
has severalsuch collectionsof neurons, each using a particular neuro-
transmitter and making widely dispersed,diffuse, almost meanderingcon-
nections.Rather than carrying detailedsensoryinformation, thesecells of-
ten perform regulatoryfunctions,modulatingvastassemblies of postsynaptic
neurons (suchas the cerebralcortex, the thalamus,and the spinal cord) so
that they becomemore or lessexcitable,more or lesssynchronouslyactive,
and so on. collectively,they are a bit like the volume, treble,and basscon-
trols on a radio, which do not change the lyrics or melody of a song but
dramaticallyregulatethe impact of both. In addition, different systemsap-
pear to be essentialfor aspectsof motor control, memory, mood, motiva-
tion, and metabolicstate.Many psychoactivedrugs affectthesemodulatory
systems,and the systemsfigure prominently in current theoriesabout the
biologicalbasisof certain psychiatricdisorders.
F I G U RIE5 . II
Norepinephrine.containing neuronsof the locus coeruleus.The reacton of
noradrenergic neuronswith formadehyde gascausesthemto lJuoresce
green, enabling
anatom calinvest gationof ther w despread
prolect
ons.(Source:
Courtesy of Dr:KjellFuxe.)
Norepinephrinesystem
(/,
Hypothalamus
lernporat t(JtJe
a/
Locuscoeruleus-
To spinalcord
F I G U R EI 5 , I 2
The noradrenergic diffuse modulatory system arising from the locus
coeruleus. The smallclusterof ocuscoeruleusneu[onsprojectaxonsthat nnervatevast
areasof the CNS, nc ud ng the spinalcord,cerebeum,thalamus,
and cerebracortex,
" THE DIFFUSE
MODULATORY
SYSTEMS
OFTHEBRAIN 50 I
Serotonlnsystem
Basalganglia
F I G U R IE5 . I 3
The serotonergic difruse modulatory systems arising from the raphe nuclei.
alongthemidlineof the brainstemand pro1ect
The raphenucleiare clustered extensively
to all levelsof the CNS.
502 C HAPTE R I 5 . C H E M I C A L C O N T R O L O FB
TRHA
EI N A N D
BEHAVIOR
Awakening
to Dopamine
by Arvid Carlsson
Our discoveryof dopaminein the brain emergedfrom a lead to the developmentof the syndrome of Parkinson's
"Eureka!"
kind of experiment.We had treated rabbitsand disease, and that the replenishmentof DA stores by r--
mice with reserpine,a drug commonlyused in the 1950s dopa could alleviateParkinson's symptoms.Thus, for the
as an antipsychotic agent.These animalshad obvioussigns first time, a putative neurotransmitterin the CNS had
of sedationand a characteristictype of immobility known been shown to exert a profound effect on brain function
as catalepsy(FigureA, top). We then treated them with and on an important pathophysiological mechanism.
l-dopa,a precursor to norepinephrineand epinephrine. lmagineour surpriseto learn that these findingswere
We were amazedto see that within l5 minutesof an in- m e t w i t h a n a l m o s t u n a n i m o u sd i s b e l i e fb y t h e m o s t
travenousinjection of r--dopa, there was a dramatic re- prominentresearchers in this field!Among the objections
versalof the whole syndromeinducedby reserpine.The were that dopaminehad not shown any physiological ac-
animalswere up and running,fully awake,and mobile (Fig- tivity before and that this type of amine had not been
ure A, bottom). demonstratedin neurons.In addition,the prevailingview
We had previously found that following reserpine in those days was that communicationbetween nerve
treatment, NE disappearsalmost entirely from brain and c e l l s i n t h e C N S o c c u r r e d v i a e l e c t r i c a lr a t h e r t h a n
other tissues.lf the behavioralaction of reserpinewas due chemicalsignals.Fortunately,thanks to a histochemical
to depletionof NE, we reasonedit shouldbe possibleto method developedin our lab by Nils-Ake Hillarpand his
restore the behaviorby replenishing the NE stores.This colleagues, we were ableto demonstratethat DA, NE,and
could not be done by injectingNE itselfbecausethe cat- serotonin are indeed located to nerve cell bodies and
echolaminecannot cross the blood-brainbarrier.r--dopa, axons in the CNS in a fashionvery similarto the distri-
however,like many other amino acids,might be able to bution of NE in the peripheralnervoussystem.Moreover,
penetrateinto the brain and then be converted to NE by we presentedadditionalpharmacological and biochemical
the appropriateenzymes. lndeed,our experimentsseemed e v i d e n c ef o r c h e m i c a lt r a n s m i s s i o ni n t h e C N S .T h u s ,
to confirm our hypothesis.However,when we analyzed within a few years,our views on chemicaltransmissionin
the brainsof the animalsshowingthis dramaticawaken- the CNS were Senerallyaccepted,thereby heraldinga
ing response,the NE level remainedat about zero, and paradigmshift in brain research.
our hypothesiswas obviouslyfalse.
We then turned our attention to dopamine,which in
those dayswas supposedto be only a precursorto NE.We
developeda specificand sensitivechemicalmethod for as-
sayingdopamineand found that dopamineoccurs normally
in the brain in levelscomparableto NE. Dopaminestores,
like those of NE and serotonin,were depleted by reser-
pine.Unlike NE, however,the DA levelswere restored af-
ter l-dopa treatment with a time course closelyrelatedto
the awakeningresponse.Moreover,most of the dopamine
in the brain was found in the basalganglia-structuressup-
oosedto be involvedin the control of movements.ln the
meantime,we had learnedthat a common side effectof re-
serpinein humanswas a movementdisorderfaithfullymim-
ickingthe syndromeof Parkinson'sdisease.
A t a n i n t e r n a t i o n a lc a t e c h o l a m i n es y m p o s i u m i n
Bethesda,Maryland,in October 1958,we could,on the
F I G U RAE
basisof these observations, proposethat dopamineis in- Rabbits rmmobilized
by reserptne
(top) and reawakened
by dopa
volved in the control of movements.that a lack of DA can (botton). (Courtesyof ArvidCarlsson.)
V THE DIFFUSE
MODULATORY
SYSTEMS
OFTHE BMIN 503
Dopamlnesystem
I F I G U RI E
5.I4
The dopaminergicdifrusemodulatorysystemsarisingfrom the substantia
nigra and the ventral tegmental area.Thesubstantia nigraandventraltegmental
area
lieclosetogether inthemidbrain,They prolect
to thestriatum(caudate
nucleus and
putamen) andlimbicandfrontalcortical
regions,
respectively,
F I G U RI E
5.I5
The cholinergicdifrusemodulatory systemsarisingfrom the basalforebrain
and brain stem.Themedial septal
nuclei
andbasalnucleus project
of Meynert widely
uponthecerebral cortex,
including pontomesencephalotegmental
the hippocampus.The
complex projects andpartsof theforebrain.
to thethalamus
a-Methyltyrosine
\ ,t/
\ Z
Cocaineor
amphetamin€
Activatespostsynapticand Activatespostsynapticand
presynapticr€ceptors presynapticreceptors
FIGURE I5.16
Stlmulant drug actlon on the catecholamlne axon termlnal. On the left is a
noradrenergic terminaland on the right is a dopaminergic
terminal.Both neurotransmitters
are catecholamines synthesizedfrom the dietaryaminoacidtyrosine.Dopa (3,4-dihydrox-
ypheynylalanine)is an intermediatein the synthesis
of both.Theactionsof NE and DA are
usuallyterminatedby uptakebackinto the axonterminal.Amphetamineand cocaineblock
this uptake,therebyallowingNE and DA to remainin the synapticcleft longer:
CONCLUDINGREMARKS 507
,,,f'
CONCLUDING REMARKS
I n t h i s c h a p t e r ,w e h a v e e x a m i n e d t h r e e c o m p o n e n t s o f t h e n e r v o u s s y s -
tem that are characterizedby the great reach of their influences. The se-
cretory hypothalamusand autonomic nervous system communicate with
c e l l s a l l o v e r t h e b o d y , a n d t h e d i f f u s e m o d u l a t o r y s y s t e m sc o m m u n i c a t e
with neurons in many differentparts of the brain. They are alsocharacter-
ized by the duration of their direct effects,which can range fmm mir.rutes
t o h o u r s . F i n a l l y , t h e y a r e c h a r a c t e r i z e db y t h e i r c h e m i c a l n e u r o t r a n s m i t -
ters. In many instances,the transmitter definesthe system. For example, in
t h e p e r i p h e r y ,w e c a n u s e t h e w o r d s " n o r a d r e n e r g i c "a n d " s y m p a t h e t i c "i n -
t e r c h a n g e a b l yT. h e s a m e t h i n g g o e sf o r " r a p h e " a n d " s e r o t o n i n " i n t h e f o r e -
b r a i n , a n d " s u b s t a n t i an i g r a " a n d " d o p a m i n e " i n t h e b a s a l g a n g l i a .T h e s e
chemical idiosyncrasieshave allowed interpretations of drug effects on be-
h a v i o r t h a t a r e n o t p o s s i b l ew i t h m o s t o t h e r n e u r a l s y s t e m s T . hus, we have
a g o o d i d e a w h e r e i n t h e b r a i n a m p h e t a m i n e a n d c o c a i n ee x e r t t h e i r s t i n t -
ulant effects,and where in the periphery they act to raise blood pressure
and heart rate.
A t a d e t a i l e dl e v e l , e a c h o f t h e s y s t e m sd i s c u s s e di n t h i s c h a p t e rp e r f u r n t s
different functions. But at a general level, they all maintain brain homeosta-
sri: They regulate different processeswithin a certain physiological range.
F o r e x a m p l e , t h e A N S r e g u l a t e sb l o o d p r e s s u r ew i t h i n a r a n g e t h a t i s a p -
p r o p r i a t e .B l o o d p r e s s u r ev a r i a t i o n so p t i m i z e a n a n i m a l ' s p e r f o r m a n c eu n -
der different conditions. In a similar way, the noradrenergic krcus coeruleus
a n d s e r o t o n e r g i cr a p h e n u c l e i r e g u l a t e l e v e l s o f c o n s c i o u s n e s as n d m o o d .
T h e s e l e v e l sa l s o v a r y w i t h i n a r a n g e t h a t i s a d a p t i v e t o t h e o r g a n i s m .I n
t h e n e x t s e v e r a l c h a p t e r s ,w e w i l l e n c o u n t e r t h e s e s y s t e m sa g a i n i n t h e
c o n t e x t o f s p e c i f i cf u n c t i o n s .
,r/
| il'1 l. Battlefieldtraumavictimswho harelost largevolumesof blood often exprcssa cravingto drink water.Why?
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2. You'vesayed up all night tryrnt to meet a term paperdeadline.You now are typingfrantically,keepingone
eye on the paper and dre other on ttre clock How hasthe periventricularzone of the hypothalamus or-