• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • CommentGo Back
Download
 
Aaptatin nr cnitins f strss is a prir-ity fr a rganiss. Strss can b bray finas an acta r anticipat isrptin f hstasis ran anticipat thrat t -bing. Strssr-ratinfratin fr a ar snsry systs (frxap, intrcpti cs, sch as b  ansarity, an/r xtrcpti cs, sch as th sf a pratr) is cny t th brain, hich rcritsnra an nrncrin systs (ffctrs) tiniiz th nt cst t th ania. Th physigicarspns t strss ins an fficint an highy cn-sr st f intrcking systs an ais t aintainphysigic intgrity n in th st aning f circstancs.Th atnic nrs syst (ANS)
(BOX 1)
pr- is th st iiat rspns t strssr xpsr— thrgh its sypathtic an parasypathtic ars,hich prk rapi atratins in physigica statsthrgh nra innratin f n rgans. Fr xap,th sypath-arnary ar can rapiy (in sc-ns) incras hart rat an b prssr by xcitingth cariascar syst
1
. Iprtanty, xcitatin f thANS ans qicky — ing t rfx parasypathticactiatin — rsting in shrt-i rspnss.Actiatin f th hypthaaic-pititary-arncr-tica (HPA) axis rsts in atins in circating g-ccrticis
(BOX 1)
. Pak pasa gccrtici sccr tns f ints aftr th initiatin f strss
2
. Tht-stp hrna chanis f HPA inctin
(BOX 1)
 is sggish rati t th atncy f th synaptic cha-niss that ri sypath-arnary actiatin,an it nsrs that thr is an apifi an ratiy prtract scrtry pis.Th brain triggrs strss rspnss that ar cn-srat ith th natr f th stis. Physica strssrs— sch as b ss, infctin an pain — rqir aniiat ‘systic’ ractin that is triggr by rfx-i chaniss. Th brain as rspns t nn-physicar ‘psychgnic’ strssrs bas n prir xprinc rinnat prgras
3
. Ths rspnss rqir prcssingin th frbrain an can ccr in anticipatin f r inractin t strssf nts.This Ri arsss th brain circits that rgatANS an HPA axis rspnss t strss. Th first sctinris th nrcircitry, fcsing n ascning inptsfr th brainst, scning infncs fr th
limbic
 frbrain, an hypthaaic chaniss that intgratibic an brainst inpt ith rspct t hstaticfback 
(FIG. 1)
. Th scn sctin args that thstrss-cntr circitry is rrganiz in th
chronicallystrssd
brain, ining th rcritnt f s rginsan iinish infnc f thrs. Th fina sctiniscsss rap f strss circits an ths cntr-ing ry an rar, an anatica arrangntthat pris pprtnity fr ta intractin in thtiat nra intrprtatin f strssr significanc.
Stress triggers: brainstem and hypothalamus
Brainstem systems.
Th brainst rcis inpts thatsigna ar hstatic prtrbatins, sch as bss, rspiratry istrss, iscra r satic pain aninfaatin
3
. Sypathtic rspnss t ths inpts
Department of Psychiatry,University of Cincinnati,Cincinnati, Ohio45237‑0506, USA.Correspondence to J.P.H.e‑mail: james.herman@uc.edu
doi:10.1038/nrn2647Publishd onlin 13 May 2009
Limbic system
Th collction of highlyintrconnctd forbrainstructurs that ar involvd inprocssing motion andmmory.
Chronic stress
Ongoing or rpatd xposurto on or mor typs of strssstimuli ovr a priod rangingfrom days to months.
Neural regulation of endocrineand autonomic stress responses
Yvonne M. Ulrich‑Lai and James P. Herman
Abstract | The survival and well-being of all species requires appropriate physiologicalresponses to environmental and homeostatic challenges. The re-establishment andmaintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses aremediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and thebrainstem, so that the respective contributions of the neuroendocrine and autonomicsystems are tuned in accordance with stressor modality and intensity. Limbic regions that areresponsible for regulating stress responses intersect with circuits that are responsible formemory and reward, providing a means to tailor the stress response with respect to priorexperience and anticipated outcomes.
REVIEWS
NATuRe RevIewS
|
 
NeuroscieNce 
volume 10
|
juNe 2009
|
 
397
focus on stress
© 2009 Macmillan Publishers Limited. All rights reserved
 
 
Intermediolateralcolumn (T1–L2)HindbrainSacral spinal cordCardiovascular systemAbdominal visceraAdrenalmedullaAdrenal cortexPituitaryPVNMedianeminenceCRH, AVPand othersACTH
Preganglionic
Rlating to th first nuron inth two-nuron chains thatmdiat autonomic rsponss.
Postganglionic
Rlating to th scond nuronin th two-nuron chains thatmdiat autonomic rsponss.
in rfx arcs that cnicat ith aras in tha (fr xap, th rstra ntratra a)an
prganglionic
sypathtic nrns in th intr-iatra c cn f th spina cr
1
 
(FIG. 2)
.Crinat atin
 
f th parasypathtic branchf th ANS as ccrs fing strss, t atr th ‘agatn’ t th hart an ngs
1
an t hp cntr th ra-tin f atnic rspnss. This parasypathticrspns t strss is iat by th ncs abigsan th rsa tr ncs f th ags nr, pssi-by thrgh inpt fr th ncs f th sitary tract(NTS)
1
 
(FIG. 2)
. In aitin, ary an spina crsysts infr highr-rr atnic intgratisits in th hinbrain (fr xap, th raph pais,th atra parabrachia ncs an th Köikr-Fsncs), ibrain an frbrain (fr xap, thrsia hypthaas (DmH))
1
, hich atth atnic rspns t strssrs in accranc ith
Box 1 |
HPA axis and autonomic nervous system responses to stress
The sympatho-adrenomedullary (see the left-hand side of the figure) and hypothalamic-pituitary-adrenocortical (HPA)(see the right-hand side of the figure) axes are the primary systems for maintaining or reinstating homeostasis duringstress. Stressor exposure results in activation of preganglionic sympathetic neurons in the intermediolateral cell columnof the thoracolumbar (T and L, respectively) spinal cord (shown in blue). These preganglionic neurons project to pre- orparavertebral ganglia that in turn project to end organs and to chromaffin cells of the adrenal medulla. This sympatheticactivation represents the classic ‘fight or flight’ response that was first characterized by Walter Cannon and colleagues inthe early twentieth century
152
; it generally increases circulating levels of adrenaline (primarily from the adrenal medulla)and noradrenaline (primarily from sympathetic nerves), heart rate and force of contraction, peripheral vasoconstriction, andenergy mobilization. Parasympathetic tone can also be modulated during stress. In the parasympathetic system (shown inred), activation of craniosacral preganglionic nuclei activates
postganglionic
nuclei located in or near the end organs thatthey innervate; parasympathetic actions are generally opposite to those of the sympathetic system.For the HPA axis, stressor exposure activates hypophysiotrophic neurons in the paraventricular nucleus of thehypothalamus that secrete releasing hormones, such as corticotropin-releasing hormone (CRH) and arginine vasopressin(AVP), into the portal circulation of the median eminence. These releasing hormones act on the anterior pituitary topromote the secretion of adrenocorticotropic hormone (ACTH), which in turn acts on the inner adrenal cortex (that is, thezona fasciculata) to initiate the synthesis and release of glucocorticoid hormones (for example, corticosterone in rats andcortisol in humans). Circulating glucocorticoids then promote the mobilization of stored energy and potentiate numeroussympathetically mediated effects, such as peripheral vasoconstriction. Moreover, the adrenal cortex is directly innervatedby the sympathetic nervous system, which can regulate corticosteroid release
153
. Thus, the HPA axis and sympatheticsystem have largely complementary actions throughout the body, including energy mobilization and maintenance of blood pressure during stress.
reVIeWs
398
|
juNe 2009
|
volume 10
www.nat.m/w/n
 
reVIeWs
© 2009 Macmillan Publishers Limited. All rights reserved
 
 Stress signals
•Experiential
factors
•
Inna
te pr
ogrammes
Ongoing homeostaticfeedbackStress signals
•
Homeosta
tic imbalanc
e
•
Pain
•
Inflammation
Top-down regulation
Limbic
for
ebr
ain
‘Middle management’
BS
T and hypothalamus
Stress response triggers
Brainstem
Hypothalamus
CVO
Output systems
HP
A acti
vat
ion (PVN
)
SAM acti
vat
ion (ANS)
Subfornical organ
A forbrain circumvntricularorgan that lacks a blood–brainbarrir.
Preautonomic
Rlating to th CNS nuronsthat ar involvd in rgulatingprganglionic sympathtic orparasympathtic nurons inth spinal cord and/orbrainstm.
FOS 
An immdiat arly gn,xprssion of which is tightlylinkd to rcnt cllularxcitation.
scning infratin fr th hypthaas anth ibic frbrain. Athgh a f ths circits par-ticipat in atnic intgratin, thir prcis r(s) instrss-inc rspnss is nt yt fin.Signas f hstatic ibaanc in th brainstas a t actiatin f th HPA axis: ascning brain-st (an prhaps spina) pathays prct haiy t th parcar iisins f th parantricarncs f th hypthaas (PvN)
(FIG. 3)
. Fr xa-p, catchainrgic (sch as nrarnrgic anarnrgic) prctins t th hypphysitrphic znf th PvN riginat in th NTS an C1–C3 rgins
4,5
 an participat in HPA actiatin
6
. NTS prctins tthis ara ras aitina nracti factrs (inc-ing nrppti Y, gcagn-ik ppti 1, inhibin-β,satstatin an nkphain
7–9
) that can rgat HPAactiatin. In s bt nt a NTS nrns ths factrsar ccaiz ith nrarnain an arnain
8
.Dstrctin f ascning nrarnain an arna-in nrns rcs HPA axis rspnss t stii thatsigna hstatic prtrbatins (fr xap, hypgy-caia r intrkin 1β inctin)
10,11
bt s ntaffct psychgnic rspnss. Ths, it as prps thatascning catchainrgic pathays iat systic-strss rspnss
3
. Hr, s nn-catchainrgicNTS c grps (fr xap, gcagn-ik ppti 1nrns)
12
ar in in gnrating HPA rspnss tbth psychgnic an systic strssrs, sggsting thatthr is s gr f fnctina spciaizatin angNTS an PvN pathays.Th parcar PvN as rcis srtnrgicinnratin fr th ian raph nci in th i-brain. Srtnin actiats th HPA axis
13
by actiatingsrtnin 2A rcptrs n PvN nrns
14
. Srtnrgicfibrs prct qay t th PvN an srrningrgins
15
, raising th pssibiity that srtnin asinfncs ca circit nrns that prct t th PvN.
Circumventricular organs: integration of peripheral signals.
Cpnnts f th aina trinais systin th frbrain (that is, th ian prptic ncs,th
subfornical organ
an th rgan ascs f th aina trinais) rspn t prtrbatins in fian ctryt baanc an b prssr. This systis ssntia fr th cntra rgatin f b prssrby angitnsin II. Th sbfrnica rgan
16
has irctangitnsin II-cntaining prctins t th iaparcar PvN, hr it stiats HPA axis acti-ity by actiating th angitnsin II typ I rcptr
17
. Thaina trinais as prcts t thr hypthaaicstrctrs, incing th antrntra prptic ncs,th DmH an th
prautonomic
PvN
18
, thrgh hichit can initiat strss-inc changs in cariascaractiity 
19
.
Paraventricular and dorsomedial hypothalamicnuclei.
Ang sra hypthaaic nci that arircty in in rgating HPA axis an atnicrspnss t strssrs, th PvN stans t as a princi-pa intgratr f strss signas. Th PvN hss istinctppatins f nrns that prct t th ian i-nnc an t atnic targts in th brainst anspina cr sch as th intriatra c cn,th parabrachia ncs, th rsa tr ncsf th ags nr an th NTS
20
. Transnrna tracingstis inicat that parasypathtic an sypathticprctin nrns ar intring in th PvN, sg-gsting that ths nrns inpt int bth ars f ANSfnctin
21
.Th PvN is haiy innrat by GABA (γ-ain-btyric aci)-rgic inpts
22
, hich pri a sbstantiainhibitry tn
23,24
 
(FIGS 3,4)
. S f th GABArgicinnratin t th PvN cs fr nrns in thpri-PvN rgin
25
, hich in trn is targt by sraibic brain rgins, nabing it t transat ibic infr-atin int atin f th HPA axis r atnicactiatin
26
.Th DmH rgats atnic an prhaps as HPAaxis rspnss t psychgnic stii. lca stiatinf th DmH incrass hart rat, b prssr an HPAaxis rspnss t a psychgica strssr
27
, hras inhi-bitin attnats strss-inc incrass in hart rat anb prssr
28
. Hr, inactiatin f th DmH snt affct cariascar rspnss t harrhag
28
, ini-cating that hypaic stii ar prcss shr(st iky thrgh brainst rfx pathays). ThDmH ight as b in in gating PvN actiatin:ca inhibitin f th rsa DmH rcs arncrti-ctrpic hrn (ACTH) ras an nra xcitatin(as rfct by actiatin f th iiat ary gn
FOS
29
) in th parcar PvN t psychgnic bt ntsystic stii
30
. mrr, th ntra DmH inhibitsnrna actiity in th PvN
31
, inicating that th DmHcntains anaticay sgrgat nrna ppatinsthat actiat r inhibit HPA axis actiity 
(FIG. 3)
.
Figure 1 |
Gna hm  ban at-t gaty pathway.
Stressorsactivate brainstem and/or forebrain limbic structures. The brainstem can generate rapidhypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS)responses through direct projections to hypophysiotrophic neurons in theparaventricular nucleus of the hypothalamus (PVN) or to preganglionic autonomicneurons (stress response triggers). By contrast, forebrain limbic regions have no directconnections with the HPA axis or the ANS and thus require intervening synapses beforethey can access autonomic or neuroendocrine neurons (top-down regulation). A highproportion of these intervening neurons are located in hypothalamic nuclei that are alsoresponsive to homeostatic status, providing a mechanism by which the descendinglimbic information can be modulated according to the physiological status of the animal(‘middle management’). BST, bed nucleus of the stria terminalis; CVO, circumventricularorgan; SAM, sympathoadrenomedullary system.
reVIeWs
NATuRe RevIewS
|
 
NeuroscieNce 
volume 10
|
juNe 2009
|
 
399
focus
 
on stress
© 2009 Macmillan Publishers Limited. All rights reserved
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
You must be to leave a comment.
Submit
Characters: ...