Advertisement

Brain Structure and Function

, Volume 217, Issue 1, pp 5–17 | Cite as

Synaptology of ventral CA1 and subiculum projections to the basomedial nucleus of the amygdala in the mouse: relation to GABAergic interneurons

  • M. Müller
  • H. Faber-Zuschratter
  • Y. Yanagawa
  • O. Stork
  • H. Schwegler
  • Rüdiger LinkeEmail author
Original Article

Abstract

GABAergic neurons of the amygdala are thought to play a critical role in establishing networks for feedback and feedforward inhibition and in mediating rhythmic network activity patterns relevant for emotional behavior, determination of stimulus salience, and memory strength under stressful experiences. These functions are typically fulfilled in interplay of amygdala and hippocampus. Therefore, we explored the putative connectivity of GABAergic neurons with the hippocampo-amygdalar projection with the anterograde tracers Phaseolus vulgaris leucoagglutinin (Phal) and Miniruby injected to GAD67-GFP knock-in mice in which GABAergic neurons are labeled by the expression of the gene for green fluorescent protein (GFP) inserted to the GAD1 gene locus (Tamamaki et al. J Comp Neurol 467:60–79, 2003). We found that, while hippocampal axons target all nuclei of the amygdala, the densest fiber plexus was found in the posterior basomedial nucleus. Electron microscopy revealed that the vast majority of contacts in this nucleus were formed by thin fibers making small asymmetrical contacts, predominantly on GFP-negative profiles. However, several asymmetrical contacts could also be seen on GFP-positive profiles. A surprising result was the occasional occurrence of anterogradely labeled symmetrical synapses indicating a GABAergic contribution to the projection from the hippocampus to the amygdala. While hippocampal input to the amygdala appears to be largely excitatory and targets non-GABAergic neurons, our data provide evidence for a direct involvement of GABAergic neurons in the interplay of these regions, either as target in the amygdala or as projection neurons from the hippocampus. These particular “interface neurons” may be of relevance for the information processing in the amygdalo-hippocampal system involved in emotional behavior and memory formation.

Keywords

Amygdala Hippocampus GABA GAD GFP Synapse Electron microscopy 

Notes

Acknowledgments

We thank S. Röhl for excellent technical support. Supported by SFB 779-B5 (M.M., H.F.-Z., O.S.,H.S., R.L.) and Grant-in-Aids for Scientific Research from the MEXT, Japan and Takeda Science Foundation (Y.Y.).

Conflict of interest

The authors declare that they have no conflict of interest

References

  1. Adams JC (1981) Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem 29:775PubMedCrossRefGoogle Scholar
  2. Albrecht A, Bergado-Acosta JR, Pape HC, Stork O (2010) Role of the neural cell adhesion molecule (NCAM) in amygdalo-hippocampal interactions and salience determination of contextual fear memory. Int J Neuropsychopharmacol 13:661–674PubMedCrossRefGoogle Scholar
  3. Alvarez RP, Biggs A, Chen G, Pine DS, Grillon C (2008) contextual fear conditioning in humans: cortical-hippocampal and amygdala contributions. J Neurosci 28:6211–6219PubMedCrossRefGoogle Scholar
  4. Bergado-Acosta JR, Sangha S, Narayanan RT, Obata K, Pape HC, Stork O (2008) Critical role of the 65-kDa isoform of glutamic acid decarboxylase in consolidation and generalization of Pavlovian fear memory. Learn Mem 15:163–171PubMedCrossRefGoogle Scholar
  5. Bissiere S, Humeau Y, Luthi A (2003) Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci 6:587–592PubMedCrossRefGoogle Scholar
  6. Brinley-Reed M, Mascagni F, McDonald AJ (1995) Synaptology of prefrontal cortical projections to the basolateral amygdala: an electron microscopic study in the rat. Neurosci Lett 202:45–48PubMedCrossRefGoogle Scholar
  7. Canteras NS, Swanson LW (1992) Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHA-L anterograde tract-tracing study in the rat. J Comp Neurol 324:180–194PubMedCrossRefGoogle Scholar
  8. Carlsen J (1988) Immunocytochemical localization of glutamate decarboxylase in the rat basolateral amygdaloid nucleus, with special reference to GABAergic innervation of amygdalostriatal projection neurons. J Comp Neurol 273:513–526PubMedCrossRefGoogle Scholar
  9. Carlsen J, Heimer L (1988) The basolateral amygdaloid complex as a cortical-like structure. Brain Res 441:377–380PubMedCrossRefGoogle Scholar
  10. Cenquizca LA, Swanson LW (2007) Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res Rev 56:1–26PubMedCrossRefGoogle Scholar
  11. Chen S, Aston-Jones G (1998) Axonal collateral-collateral transport of tract tracers in brain neurons: false anterograde labelling and useful tool. Neuroscience 82:1151–1163PubMedCrossRefGoogle Scholar
  12. Ehrlich I, Humeau Y, Grenier F, Ciocchi S, Herry C, Lüthi A (2009) Amygdala inhibitory circuits and the control of fear memory. Neuron 62:757–771PubMedCrossRefGoogle Scholar
  13. Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19PubMedCrossRefGoogle Scholar
  14. Franklin KBJ, Paxinos G (2007) The mouse brain in stereotaxic coordinates. Elsevier, New YorkGoogle Scholar
  15. Gerfen CR, Sawchenko PE (1984) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: Immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris Leucoagglutinin (PHA-L). Brain Res 290:219–238PubMedCrossRefGoogle Scholar
  16. Groenewegen HJ, Wouterlood FG (1990) Light and electron microscopic tracing of neuronal connections with Phaseolus vulgaris-leucoagglutinin (PHA-L), and combinations with other neuroanatomical techniques. In: Björklund A, Hökfelt T, Wouterlood FG, van den Pol AN (eds) Handbook of chemical neuroanatomy, Vol. 8: Analysis of neuronal microcircuits and synaptic interactions. Elsevier Science Publishers B.V, Amsterdam, pp 47–124Google Scholar
  17. Hajos F, Staiger JF, Halasy K, Freund TF, Zilles K (1997) Geniculo-cortical afferents form synaptic contacts with vasoactive intestinal polypeptide (VIP) immunoreactive neurons of the rat visual cortex. Neurosci Lett 228:179–182PubMedCrossRefGoogle Scholar
  18. Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A, Brown RA, Neve RL, Guzowski JF, Silva AJ, Josselyn SA (2007) Neuronal competition and selection during memory formation. Science 316:457–460PubMedCrossRefGoogle Scholar
  19. Herry C, Ciocchi S, Senn V, Demmou L, Muller C, Lüthi A (2008) Switching on and off fear by distinct neuronal circuits. Nature 454:600–606PubMedCrossRefGoogle Scholar
  20. Hobin JA, Ji J, Maren S (2006) Ventral hippocampal muscimol disrupts context-specific fear memory retrieval after extinction in rats. Hippocampus 16:174–182PubMedCrossRefGoogle Scholar
  21. Ji J, Maren S (2007) Hippocampal involvement in contextual modulation of fear extinction. Hippocampus 17:749–758PubMedCrossRefGoogle Scholar
  22. Jinno S (2009) Structural organization of long-range GABAergic projection system of the hippocampus. Front Neuroanat 3. doi: 10.3389/neuro.05.013.2009
  23. Jinno S, Klausberger T, Marton LF, Dalezios Y, Roberts JD, Fuentealba P, Bushong EA, Henze D, Buzsaki G, Somogyi P (2007) Neuronal diversity in GABAergic long-range projections from the hippocampus. J Neurosci 27:8790–8804PubMedCrossRefGoogle Scholar
  24. Kaneko K, Tamamaki N, Owada H, Kakizaki T, Kume N, Totsuka M, Yamamoto T, Yawo H, Yagi T, Obata K, Yanagawa Y (2008) Noradrenergic excitation of a subpopulation of GABAergic cells in the basolateral amygdala via both activation of nonselective cationic conductance and suppression of resting K+ conductance: a study using glutamate decarboxylase 67-green fluorescent protein knock-in mice. Neuroscience 157:781–797PubMedCrossRefGoogle Scholar
  25. Kishi T, Tsumori T, Yokota S, Yasui Y (2006) Topographical projection from the hippocampal formation to the amygdala: a combined anterograde and retrograde tracing study in the rat. J Comp Neurol 496:349–368PubMedCrossRefGoogle Scholar
  26. Lanciego JL, Wouterlood FG (2006) Multiple neuroanatomical tract-tracing: approaches for multiple tract tracing. In: Zaborszky L, Wouterlood FG, Lanciego JL (eds) Neuroanatomical tract-tracing 3. Molecules, neurons, and systems. Springer, New York, pp 336–363CrossRefGoogle Scholar
  27. LeDoux JE (2000) Emotion circuits in the brain. Ann Rev Neurosci 23:155–184PubMedCrossRefGoogle Scholar
  28. LeDoux JE, Farb CR, Milner TA (1991) Ultrastructure and synaptic associations of auditory thalamo-amygdala projections in the rat. Exp Brain Res 85:577–586PubMedCrossRefGoogle Scholar
  29. Li R, Nishijo H, Ono T, Ohtani Y, Ohtani O (2002) Synapses on GABAergic neurons in the basolateral nucleus of the rat amygdala: double-labeling immunoelectron microscopy. Synapse 43:42–50PubMedCrossRefGoogle Scholar
  30. Makkar SR, Zhang SQ, Cranney J (2010) Behavioral and neural analysis of GABA in the acquisition, consolidation, reconsolidation, and extinction of fear memory. Neuropsychopharmacology 35:1625–1652PubMedGoogle Scholar
  31. Maren S, Hobin JA (2007) Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala. Learn Mem 14:318–324PubMedCrossRefGoogle Scholar
  32. McDonald AJ (1982) Neurons of the lateral and basolateral amygdaloid nuclei: a Golgi study in the rat. J Comp Neurol 212:293–312PubMedCrossRefGoogle Scholar
  33. Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T (2008) Identification of a Neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus. PLoS ONE 3(7):e2695. doi:10.1371/journal.pone.0002695
  34. Moser M-B, Moser EI (1998) Functional differentiation in the hippocampus. Hippocampus 8:608–619PubMedCrossRefGoogle Scholar
  35. Muller JF, Mascagni F, McDonald AJ (2003) Synaptic connections of distinct interneuronal subpopulations in the rat basolateral amygdalar nucleus. J Comp Neurol 456:217–236PubMedCrossRefGoogle Scholar
  36. Muller JF, Mascagni F, McDonald AJ (2007) Serotonin-immunoreactive axon terminals innervate pyramidal cells and interneurons in the rat basolateral amygdala. J Comp Neurol 505:314–335PubMedCrossRefGoogle Scholar
  37. Muller JF, Mascagni F, McDonald AJ (2011) Cholinergic innervation of pyramidal cells and parvalbumin-immunoreactive interneurons in the rat basolateral amygdala. J Comp Neurol 519:790–805PubMedCrossRefGoogle Scholar
  38. Ottersen OP (1982) Connections of the amygdala of the rat. IV. Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase. J Comp Neurol 205:30–48PubMedCrossRefGoogle Scholar
  39. Pape HC, Pare D (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419–463PubMedCrossRefGoogle Scholar
  40. Peters A, Palay SL, Webster HD (1991) The fine structure of the nervous system. Oxford University Press, New YorkGoogle Scholar
  41. Pinard CR, Muller JF, Mascagni F, McDonald AJ (2008) Dopaminergic innervation of interneurons in the rat basolateral amygdala. Neuroscience 157:850–863PubMedCrossRefGoogle Scholar
  42. Pitkänen A, Pikkarainen M, Nurminen N, Ylinen A (2000) Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex. Ann N Y Acad Sci 911:369–391PubMedCrossRefGoogle Scholar
  43. Rainnie DG, Asprodini EK, Shinnick-Gallagher P (1991) Inhibitory transmission in the basolateral amygdala. J Neurophysiol 66:999–1009PubMedGoogle Scholar
  44. Repa JC, Muller J, Apergis J, Desrochers TM, Zhou Y, LeDoux JE (2001) Two different lateral amygdala cell populations contribute to the initiation and storage of memory. Nat Neurosci 4:724–731PubMedCrossRefGoogle Scholar
  45. Richter-Levin G, Akirav I (2000) Amygdala-hippocampus dynamic interaction in relation to memory. Mol Neurobiol 22:11–20PubMedCrossRefGoogle Scholar
  46. Roberts GW (1992) Neuropeptides: cellular morphology, major pathways, and functional considerations. In: Aggleton JP (ed) The amagdala. Neurobiological aspects of emotion, memory, amd mental dysfunction. Wiley-Liss, New York, pp 115–142Google Scholar
  47. Royer S, Martina M, Paré D (1999) An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci 19:10575–10583PubMedGoogle Scholar
  48. Rudy JW, Matus-Amat P (2005) The ventral hippocampus supports a memory representation of context and contextual fear conditioning: implications for a unitary function of the hippocampus. Behav Neurosci 119:154–163PubMedCrossRefGoogle Scholar
  49. Samson RD, Dumont EC, Pare D (2003) Feedback inhibition defines transverse processing modules in the lateral amygdala. J Neurosci 23:1966–1973PubMedGoogle Scholar
  50. Segal M, Richter-Levin G, Maggio N (2010) Stress-induced dynamic routing of hippocampal connectivity: a hypothesis. Hippocampus 20:1332–1338PubMedCrossRefGoogle Scholar
  51. Seidenbecher T, Laxmi TR, Stork O, Pape HC (2003) Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301:846–850PubMedCrossRefGoogle Scholar
  52. Shaban H, Humeau Y, Herry C, Cassasus G, Shigemoto R, Ciocchi S, Barbieri S, van der Putten H, Kaupmann K, Bettler B, Lüthi A (2006) Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition. Nat Neurosci 9:1028–1035PubMedCrossRefGoogle Scholar
  53. Smith Y, Paré J-F, Paré D (1998) Cat intraamygdaloid inhibitory network: ultrastructural organization of parvalbumin-immunoreactive elements. J Comp Neurol 391:164–179PubMedCrossRefGoogle Scholar
  54. Smith Y, Paré J-F, Paré D (2000) Differential innervation of parvalbumin-immunoreactive interneurons of the basolateral amygdaloid complex by cortical and intrinsic inputs. J Comp Neurol 416:496–508PubMedCrossRefGoogle Scholar
  55. Sosulina L, Graebenitz S, Pape HC (2010) GABAergic interneurons in the mouse lateral amygdala: a classification study. J Neurophysiol. doi: 10.1152/jn.00207.2010
  56. Stoppel C, Albrecht A, Pape HC, Stork O (2006) Genes and neurons: molecular insights to fear and anxiety. Genes Brain Behav 5:34–47PubMedCrossRefGoogle Scholar
  57. Sutherland RJ, O’Brien J, Lehmann H (2008) Absence of systems consolidation of fear memories after dorsal, ventral, or complete hippocampal damage. Hippocampus 18:710–718PubMedCrossRefGoogle Scholar
  58. Szinyei C, Heinbockel T, Montagne J, Pape H-C (2000) Putative cortical and thalamic inputs elicit convergent excitation in a population of GABAergic interneurons of the lateral amygdala. J Neurosci 20:8909–8915PubMedGoogle Scholar
  59. Szinyei C, Stork O, Pape HC (2003) Contribution of NR2B subunits to synaptic transmission in amygdaloid interneurons. J Neurosci 23:2549–2556PubMedGoogle Scholar
  60. Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J-I, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60–79PubMedCrossRefGoogle Scholar
  61. Truitt WA, Johnson PL, Dietrich AD, Fitz SD, Shekhar A (2009) Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala. Neuroscience 160:284–294PubMedCrossRefGoogle Scholar
  62. Valverde F (1962) Intrinsic organization of the amygdaloid complex. A Golgi study in the mouse. Trab Inst Cajal Invest Biol 54:291–314Google Scholar
  63. Van Groen T, Wyss JM (1990) Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections. J Comp Neurol 302:515–528PubMedCrossRefGoogle Scholar
  64. Woodruff AR, Sah P (2007a) Inhibition and synchronization of basal amygdala principal neuron spiking by parvalbumin-positive interneurons. J Neurophysiol 98:2956–2961PubMedCrossRefGoogle Scholar
  65. Woodruff AR, Sah P (2007b) Networks of parvalbumin-positive interneurons in the basolateral amygdala. J Neurosci 27:553–563PubMedCrossRefGoogle Scholar
  66. Wouterlood FG, Jorritsma-Byham B (1993) The anterograde neuroanatomical tracer biotinylated dextran-amine: comparison with the tracer Phaseolus vulgaris-leucoagglutinin in preparations for electron microscopy. J Neurosci Meth 48:75–87CrossRefGoogle Scholar
  67. Yilmazer-Hanke DM, Hantsch M, Hanke J, Schulz C, Faber-Zuschratter H, Schwegler H (2004) Neonatal thyroxine treatment: changes in the number of corticotropin-releasing-factor (CRF) and neuropeptide Y (NPY) containing neurons and density of tyrosine hydroxylase positive fibers (TH) in the amygdala correlate with anxiety-related behavior of wistar rats. Neuroscience 124:283–297PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • M. Müller
    • 1
  • H. Faber-Zuschratter
    • 1
  • Y. Yanagawa
    • 2
    • 3
  • O. Stork
    • 4
  • H. Schwegler
    • 1
  • Rüdiger Linke
    • 1
    Email author
  1. 1.Institute of AnatomyOtto-von-Guericke UniversityMagdeburgGermany
  2. 2.Department of Genetic and Behavioral NeuroscienceGumma UniversityMaebashiJapan
  3. 3.Japan Science and Technology AgencyCRESTTokyoJapan
  4. 4.Department of Genetics and Molecular Neurobiology, Institute of BiologyOtto-von-Guericke UniversityMagdeburgGermany

Personalised recommendations