Brain Structure and Function

, Volume 218, Issue 1, pp 187–208

Common and distinct neural inputs to the medial central nucleus of the amygdala and anterior ventrolateral bed nucleus of stria terminalis in rats

Original Article

Abstract

The central nucleus of the amygdala (CEA) and lateral bed nucleus of stria terminalis (BST) are highly interconnected limbic forebrain regions that share similar connectivity with other brain regions that coordinate behavioral and physiological responses to internal and environmental stressors. Their similar connectivity is frequently referred to when describing the CEA and lateral BST together as a unified “central extended amygdala”. However, the CEA and BST reportedly play distinct roles in behavioral and physiological responses associated with fear, anxiety, and social defeat, presumably due to differences in connectivity. To identify common and unique sources of input to the CEA and lateral BST, we performed dual retrograde tracing. Fluorogold and cholera toxin β were iontophoresed into the medial CEA (CEAm) and the anterior ventrolateral BST (BSTvl) of adult male rats. The anatomical distribution of tracer-labeled neurons was mapped throughout the brain. Regions with overlapping populations of CEAm- and BSTvl-projecting neurons were further examined for the presence of double-labeled neurons. Although most regions with input to the mCEA also projected to the BSTvl, and vice versa, cortical and sensory system-related regions projected more robustly to the CEAm, while motor system-related regions primarily innervated the BSTvl. The incidence of double-labeled neurons with collateralized axonal inputs to the CEAm and BSTvl was relatively small (~2 to 13%) and varied across regions, suggesting regional differences in the degree of coordinated CEAm and BSTvl input. The demonstrated similarities and differences in inputs to CEAm and BSTvl provide new anatomical insights into the functional organization of these limbic forebrain regions.

Keywords

Limbic system Extended amygdala Axon collateralization Dual retrograde tracing 

Abbreviations

ACBsh

Nucleus accumbens, shell division

aco

Anterior commissure

AI

Agranular insular cortex

amc

Amygdalar capsule

AP

Area postrema

AStr

Amygdala-striatal transition area

Aud

Auditory thalamus

BLAp

Basolateral amygdalar nucleus, posterior part

BMA

Basomedial amygdalar nucleus

BST

Bed nucleus of stria terminalis

pBST

Posterior subnuclei group of the bed nucleus of stria terminalis

BSTvl

Ventrolateral subnuclei group of the bed nucleus of stria terminalis

CA1

Field CA1, Ammon’s horn

cc

Corpus callosum

CEA

Central amygdalar nucleus

CEAm

Central amygdalar nucleus, medial part

CEAl

Central amygdalar nucleus, lateral part

CLI

Central linear nucleus raphé

cpd

Cerebral peduncle

DI

Dysgranular insular cortex

DMX

Dorsal motor nucleus of the vagus

DR

Dorsal nucleus raphé

dscp

Superior cerebellar peduncle decussation

ec

External capsule

fx

Fornix

ILA

Infralimbic area

IMD

Intermediodorsal nucleus thalamus

IPAC

Interstitial nucleus of the posterior limb of the anterior commissure

LHA

Lateral hypothalamic area

LS

Lateral septal nucleus

mcp

Middle cerebellar peduncle

MD

Mediodorsal nucleus thalamus

ml

Medial lemniscus

mlf

Medial longitudinal fascicle

mPFC

Medial prefrontal cortex

MPO

Medial preoptic area

MTN

Midline thalamic nuclei

NLOT

Nucleus of the lateral olfactory tract

NTS

Nucleus of the solitary tract

och

Optic chiasm

opt

Optic tract

PA

Posterior amygdalar nucleus

PAGvl

Periaqueductal gray, ventrolateral division

PB

Parabrachial nucleus

PBle

Parabrachial nucleus, external lateral part

PBlv

Parabrachial nucleus, ventral lateral part

PBm

Parabrachial nucleus, medial part

PBw

Parabrachial nucleus, waist part

PL

Prelimbic area

PPN

Pedunculopontine nucleus

PSTN

Parasubthalamic nucleus

PVN

Paraventricular hypothalamic nucleus

PVT

Paraventricular thalamic nucleus

py

Pyramid

scp

Superior cerebellar peduncle

SI

Substantia innominata

sm

Stria medullaris

SNc

Substantia nigra, compact part

SNr

Substantia nigra, reticular part

SPFpm

Subparafascicular nucleus thalamus, parvicellular part, medial division

st

Stria terminalis

STN

Subthalamic nucleus

TR

Postpiriform transition area

V4

Fourth ventricle

VLM

Ventrolateral medulla

VP

Ventral pallidum

VPMpc

Ventral posteromedial nucleus thalamus, parvicellular part

VTA

Ventral tegmental area

References

  1. Alheid G, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 1:1–39CrossRefGoogle Scholar
  2. Altschuler SM, Bao X, Bieger D, Hopkins DA, Miselis RR (1989) Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts. J Comp Neurol 283(2):248–268. doi:10.1002/cne.902830207 PubMedCrossRefGoogle Scholar
  3. Bhatnagar S, Dallman M (1998) Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neuroscience 84(4):1025–1039PubMedCrossRefGoogle Scholar
  4. Bhatnagar S, Huber R, Nowak N, Trotter P (2002) Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint. J Neuroendocrinol 14(5):403–410. doi:10.1046/j.0007-1331.2002.00792.x PubMedCrossRefGoogle Scholar
  5. Bhatnagar S, Huber R, Lazar E, Pych L, Vining C (2003) Chronic stress alters behavior in the conditioned defensive burying test: role of the posterior paraventricular thalamus. Pharmacol Biochem Behav 76(2):343–349. doi:10.1016/j.pbb.2003.08.005 PubMedCrossRefGoogle Scholar
  6. Cecchi M, Khoshbouei H, Javors M, Morilak DA (2002) Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress. Neuroscience 112(1):13–21PubMedCrossRefGoogle Scholar
  7. Chiba T, Kayahara T, Nakano K (2001) Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey Macaca fuscata. Brain Res 888(1):83–101. doi:10.1016/s0006-8993(00)03013-4 PubMedCrossRefGoogle Scholar
  8. Ciccocioppo R, Fedeli A, Economidou D, Policani F, Weiss F, Massi M (2003) The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ. J Neurosci 23(28):9445–9451PubMedGoogle Scholar
  9. Ciriello J, Schultz CG, Roder S (1994) Collateral axonal projections from ventrolateral medullary non-catecholaminergic neurons to central nucleus of the amygdala. Brain Res 663(2):346–351PubMedCrossRefGoogle Scholar
  10. Ciriello J, Solano-Flores LP, Rosas-Arellano MP, Kirouac GJ, Babic T (2008) Medullary pathways mediating the parasubthalamic nucleus depressor response. Am J Physiol Regul Integr Comp Physiol 294(4):R1276–R1284. doi:10.1152/ajpregu.00437.2007 PubMedCrossRefGoogle Scholar
  11. Cullinan WE, Herman JP, Watson SJ (1993) Ventral subicular interaction with the hypothalamic paraventricular nucleus: evidence for a relay in the bed nucleus of the stria terminalis. J Comp Neurol 332(1):1–20. doi:10.1002/cne.903320102 PubMedCrossRefGoogle Scholar
  12. Cullinan W, Ziegler D, Herman J (2008) Functional role of local GABAergic influences on the HPA axis. Brain Struct Funct 213(1):63–72. doi:10.1007/s00429-008-0192-2 PubMedCrossRefGoogle Scholar
  13. de Olmos J, Heimer L (1999) The concepts of the ventral striatopallidal system and extended amygdala. Annals of the New York Academy of Sciences (Advancing from the Ventral Striatum to the Extended Amygdala: Implications for Neuropsychiatry and Drug Abuse) 877:1–32Google Scholar
  14. DeVito JL, Anderson ME, Walsh KE (1980) A horseradish peroxidase study of afferent connections of the globus pallidus in Macaca mulatta. Exp Brain Res 38(1):65–73. doi:10.1007/bf00237932 PubMedCrossRefGoogle Scholar
  15. Deyama S, Nakagawa T, Kaneko S, Uehara T, Minami M (2007) Involvement of the bed nucleus of the stria terminalis in the negative affective component of visceral and somatic pain in rats. Behav Brain Res 176:367–371PubMedCrossRefGoogle Scholar
  16. Dong HW, Swanson LW (2003) Projections from the rhomboid nucleus of the bed nuclei of the stria terminalis: implications for cerebral hemisphere regulation of ingestive behaviors. J Comp Neurol 463(4):434–472PubMedCrossRefGoogle Scholar
  17. Dong HW, Swanson LW (2004) Organization of axonal projections from the anterolateral area of the bed nuclei of the stria terminalis. J Comp Neurol 468(2):277–298PubMedCrossRefGoogle Scholar
  18. Dong HW, Swanson LW (2006a) Projections from bed nuclei of the stria terminalis, anteromedial area: cerebral hemisphere integration of neuroendocrine, autonomic, and behavioral aspects of energy balance. J Comp Neurol 494(1):142–178PubMedCrossRefGoogle Scholar
  19. Dong HW, Swanson LW (2006b) Projections from bed nuclei of the stria terminalis, dorsomedial nucleus: implications for cerebral hemisphere integration of neuroendocrine, autonomic, and drinking responses. J Comp Neurol 494(1):75–107PubMedCrossRefGoogle Scholar
  20. Dong HW, Petrovich GD, Swanson LW (2000) Organization of projections from the juxtacapsular nucleus of the BST: a PHAL study in the rat. Brain Res 859(1):1–14PubMedCrossRefGoogle Scholar
  21. Dong HW, Petrovich GD, Swanson LW (2001a) Topography of projections from amygdala to bed nuclei of the stria terminalis. Brain Res Rev 38(1–2):192–246. doi:10.1016/s0165-0173(01)00079-0 PubMedCrossRefGoogle Scholar
  22. Dong HW, Petrovich GD, Watts AG, Swanson LW (2001b) Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain. J Comp Neurol 436(4):430–455PubMedCrossRefGoogle Scholar
  23. Fanselow MS, LeDoux JE (1999) Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 23(2):229–232PubMedCrossRefGoogle Scholar
  24. Fendt M, Fanselow MS (1999) The neuroanatomical and neurochemical basis of conditioned fear. Neurosci Biobehav Rev 23(5):743–760PubMedCrossRefGoogle Scholar
  25. Fendt M, Endres T, Apfelbach R (2003) Temporary inactivation of the bed nucleus of the stria terminalis but not of the amygdala blocks freezing induced by trimethylthiazoline, a component of fox feces. J Neurosci 23(1):23–28PubMedGoogle Scholar
  26. Fisk GD, Wyss JM (2000) Descending projections of infralimbic cortex that mediate stimulation-evoked changes in arterial pressure. Brain Res 859(1):83–95. doi:10.1016/s0006-8993(00)01935-1 PubMedCrossRefGoogle Scholar
  27. Freedman LJ, Cassell MD (1994) Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Res 633(1–2):243–252PubMedCrossRefGoogle Scholar
  28. Funk CK, O’Dell LE, Crawford EF, Koob GF (2006) Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 26(44):11324–11332. doi:10.1523/jneurosci.3096-06.2006 PubMedCrossRefGoogle Scholar
  29. Gauriau C, Bernard J-F (2002) Pain pathways and parabrachial circuits in the rat. Exp Physiol 87(02):251–258. doi:10.1113/eph8702357 PubMedCrossRefGoogle Scholar
  30. Gaykema RPA, Chen C–C, Goehler LE (2007) Organization of immune-responsive medullary projections to the bed nucleus of the stria terminalis, central amygdala, and paraventricular nucleus of the hypothalamus: evidence for parallel viscerosensory pathways in the rat brain. Brain Res 1130:130–145PubMedCrossRefGoogle Scholar
  31. Geerling JC, Loewy AD (2006) Aldosterone-sensitive neurons in the nucleus of the solitary tract: bidirectional connections with the central nucleus of the amygdala. J Comp Neurol 497(4):646–657PubMedCrossRefGoogle Scholar
  32. Goto M, Swanson LW (2004) Axonal projections from the parasubthalamic nucleus. J Comp Neurol 469(4):581–607PubMedCrossRefGoogle Scholar
  33. Harris GC, Aston-Jones G (2007) Activation in extended amygdala corresponds to altered hedonic processing during protracted morphine withdrawal. Behav Brain Res 176(2):251–258PubMedCrossRefGoogle Scholar
  34. Heidbreder CA, Groenewegen HJ (2003) The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics. Neurosci Biobehav Rev 27(6):555–579PubMedCrossRefGoogle Scholar
  35. Hurley KM, Herbert H, Moga MM, Saper CB (1991) Efferent projections of the infralimbic cortex of the rat. J Comp Neurol 308(2):249–276. doi:10.1002/cne.903080210 PubMedCrossRefGoogle Scholar
  36. Jaferi A, Nowak N, Bhatnagar S (2003) Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus. Physiol Behav 78(3):365–373. doi:10.1016/s0031-9384(03)00014-3 PubMedCrossRefGoogle Scholar
  37. Jasnow AM, Davis M, Huhman KL (2004) Involvement of central amygdalar and bed nucleus of the stria terminalis corticotropin-releasing factor in behavioral responses to social defeat. Behav Neurosci 118(5):1052–1061PubMedCrossRefGoogle Scholar
  38. Ju G, Swanson LW (1989) Studies on the cellular architecture of the bed nuclei of the stria terminalis in the rat: I. Cytoarchitecture. J Comp Neurol 280(4):587–602. doi:10.1002/cne.902800409 PubMedCrossRefGoogle Scholar
  39. Ju G, Swanson LW, Simerly RB (1989) Studies on the cellular architecture of the bed nuclei of the stria terminalis in the rat: II. Chemoarchitecture. J Comp Neurol 280(4):603–621. doi:10.1002/cne.902800410 PubMedCrossRefGoogle Scholar
  40. Kalia M, Sullivan JM (1982) Brainstem projections of sensory and motor components of the vagus nerve in the rat. J Comp Neurol 211(3):248–264. doi:10.1002/cne.902110304 PubMedCrossRefGoogle Scholar
  41. Li S, Kirouac GJ (2008) Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J Comp Neurol 506(2):263–287. doi:10.1002/cne.21502 PubMedCrossRefGoogle Scholar
  42. Myers EA, Rinaman L (2002) Viscerosensory activation of noradrenergic inputs to the amygdala in rats. Physiol Behav 77:723–729PubMedCrossRefGoogle Scholar
  43. Nagy FZ, Pare D (2008) Timing of impulses from the central amygdala and bed nucleus of the stria terminalis to the brain stem. J Neurophysiol 100(6):3429–3436. doi:10.1152/jn.90936.2008 PubMedCrossRefGoogle Scholar
  44. Nakagawa T, Yamamoto R, Fujio M, Suzuki Y, Minami M, Satoh M, Kaneko S (2005) Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats. Neuroscience 134:9–19PubMedCrossRefGoogle Scholar
  45. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Elsevier Academic Press, San DiegoGoogle Scholar
  46. Radley JJ, Sawchenko PE (2011) A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response. J Neurosci 31(26):9683–9695. doi:10.1523/jneurosci.6040-10.2011 PubMedCrossRefGoogle Scholar
  47. Radley JJ, Arias CM, Sawchenko PE (2006) Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. J Neurosci 26(50):12967–12976. doi:10.1523/jneurosci.4297-06.2006 PubMedCrossRefGoogle Scholar
  48. Radley JJ, Gosselink KL, Sawchenko PE (2009) A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response. J Neurosci 29(22):7330–7340. doi:10.1523/jneurosci.5924-08.2009 PubMedCrossRefGoogle Scholar
  49. Reilly S (1999) The parabrachial nucleus and conditioned taste aversion. Brain Res Bull 48(3):239–254PubMedCrossRefGoogle Scholar
  50. Reynolds SM, Zahm DS (2005) Specificity in the projections of prefrontal and insular cortex to ventral striatopallidum and the extended amygdala. J Neurosci 25(50):11757–11767. doi:10.1523/jneurosci.3432-05.2005 PubMedCrossRefGoogle Scholar
  51. Roder S, Ciriello J (1994) Collateral axonal projections to limbic structures from ventrolateral medullary A1 noradrenergic neurons. Brain Res 638(1–2):182–188PubMedCrossRefGoogle Scholar
  52. Sakai N, Yamamoto T (1998) Role of the medial and lateral parabrachial nucleus in acquisition and retention of conditioned taste aversion in rats. Behav Brain Res 93(1–2):63–70PubMedCrossRefGoogle Scholar
  53. Salazar-Juárez A, Escobar C, Aguilar-Roblero R (2002) Anterior paraventricular thalamus modulates light-induced phase shifts in circadian rhythmicity in rats. Am J Physiol Regul Integr Comp Physiol 283(4):R897–R904. doi:10.1152/ajpregu.00259.2002 PubMedGoogle Scholar
  54. Santiago AC, Shammah-Lagnado SJ (2004) Efferent connections of the nucleus of the lateral olfactory tract in the rat. J Comp Neurol 471(3):314–332. doi:10.1002/cne.20028 PubMedCrossRefGoogle Scholar
  55. Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290(2):213–242. doi:10.1002/cne.902900205 PubMedCrossRefGoogle Scholar
  56. Shammah-Lagnado SJ, Alheid GF, Heimer L (1999) Afferent connections of the interstitial nucleus of the posterior limb of the anterior commissure and adjacent amygdalostriatal transition area in the rat. Neuroscience 94(4):1097–1123PubMedCrossRefGoogle Scholar
  57. Shammah-Lagnado SJ, Alheid GF, Heimer L (2001) Striatal and central extended amygdala parts of the interstitial nucleus of the posterior limb of the anterior commissure: evidence from tract-tracing techniques in the rat. J Comp Neurol 439(1):104–126PubMedCrossRefGoogle Scholar
  58. Shin J-W, Geerling JC, Loewy AD (2008) Inputs to the ventrolateral bed nucleus of the stria terminalis. J Comp Neurol 511(5):628–657PubMedCrossRefGoogle Scholar
  59. Sun N, Roberts L, Cassell MD (1991) Rat central amygdaloid nucleus projections to the bed nucleus of the stria terminalis. Brain Res Bull 27(5):651–662PubMedCrossRefGoogle Scholar
  60. Sved AF, Cano G, Card JP (2001) Neuroanatomical specificity of the circuits controlling sympathetic outflow to different targets. Clin Exp Pharmacol Physiol 28(1–2):115–119PubMedCrossRefGoogle Scholar
  61. Swanson LW (2000) Cerebral hemisphere regulation of motivated behavior. Brain Res 886(1–2):113–164PubMedCrossRefGoogle Scholar
  62. Swanson LW (2004) Brain maps: structure of the rat brain, 3rd edn. Elsevier, San DiegoGoogle Scholar
  63. Tanimoto S, Nakagawa T, Yamauchi Y, Minami M, Satoh M (2003) Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pain in rats. Eur J Neurosci 18(8):2343–2350PubMedCrossRefGoogle Scholar
  64. Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51(1):32–58. doi:10.1002/syn.10279 PubMedCrossRefGoogle Scholar
  65. Walker DL, Davis M (1997) Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. J Neurosci 17(23):9375–9383PubMedGoogle Scholar
  66. Walker DL, Toufexis DJ, Davis M (2003) Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol 463(1–3):199–216PubMedCrossRefGoogle Scholar
  67. Walker DL, Miles LA, Davis M (2009) Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses. Prog Neuropsychopharmacol Biol Psychiatry 33(8):1291–1308PubMedCrossRefGoogle Scholar
  68. Watson RE, Wiegand SJ, Clough RW, Hoffman GE (1986) Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides 7(1):155–159PubMedCrossRefGoogle Scholar
  69. Zardetto-Smith AM, Beltz TG, Johnson AK (1994) Role of the central nucleus of the amygdala and bed nucleus of the stria terminalis in experimentally-induced salt appetite. Brain Res 645(1–2):123–134. doi:10.1016/0006-8993(94)91645-4 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of PittsburghPittsburghUSA

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