Skip to main content
Log in

Routes to, from and within the subiculum

  • At-a-glance article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The subiculum is one of the major output areas of the hippocampus and has extensive projections to extrahippocampal targets. It is likely to play a pivotal role in the distribution of outgoing information from the hippocampus. The hippocampus, including the subiculum, is important for the formation, consolidation and retrieval of memory. These functions require a network that is flexible enough to encode incoming information and also allows for reliable distribution, storage and integration into previously encoded memories. Finally, relevant information has to be retrieved in a context-specific manner to allow for an appropriate behavioral response. The subiculum as a gateway between the hippocampus and cortex might serve to integrate and process information from the hippocampus proper and its other inputs before conveying it to more permanent storage locations. This review summarizes how the subiculum is embedded into upstream and downstream circuits, describes what is known about the local network topology and discusses cellular and functional properties of subicular cells subtypes. Lastly, it describes how these properties might help to separate information into parallel output streams and distribute it to its multiple target areas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aggleton JP, Christiansen K (2015) The subiculum: the heart of the extended hippocampal system. Prog Brain Res 219:65–82

    Article  PubMed  Google Scholar 

  • Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571–591

    Article  PubMed  CAS  Google Scholar 

  • Amaral DG, Dolorfo C, Alvarez-Royo P (1991) Organization of CA1 projections to the subiculum: a PHA-L analysis in the rat. Hippocampus 1:415–435

    Article  PubMed  CAS  Google Scholar 

  • Anderson MI, O’Mara SM (2003) Analysis of recordings of single-unit firing and population activity in the dorsal subiculum of unrestrained, freely moving rats. J Neurophysiol 90:655–665

    Article  PubMed  Google Scholar 

  • Behr J, Wozny C, Fidzinski P, Schmitz D (2009) Synaptic plasticity in the subiculum. Prog Neurobiol 89:334–342

    Article  PubMed  Google Scholar 

  • Böhm C, Peng P, Maier N, Winterer J, Poulet JFA, Geiger JRP, Schmitz D (2015) Functional diversity of subicular principal cells during hippocampal ripples. J Neurosci 35:13608–13618

    Article  PubMed  PubMed Central  Google Scholar 

  • Brown SP, Hestrin S (2009) Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Nature 2:1133–1136

    Article  CAS  Google Scholar 

  • Buzsáki G (1989) Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 31:551–570

    Article  PubMed  Google Scholar 

  • Cembrowski MS, Bachman J, Wang L, Sugino K, Shields B, Spruston N (2016) Spatial gene-expression gradients underlie prominent heterogeneity of CA1 pyramidal neurons. Neuron 89:351–368

    Article  PubMed  CAS  Google Scholar 

  • Chrobak JJ, Buzsáki G (1994) Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat. J Neurosci 14:6160–6170

    Article  PubMed  CAS  Google Scholar 

  • Chrobak JJ, Buzsáki G (1996) High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat. J Neurosci 16:3056–3066

    Article  PubMed  CAS  Google Scholar 

  • Deadwyler SA, Hampson RE (2004) Differential but complementary mnemonic functions of the hippocampus and subiculum. Neuron 42:465–476

    Article  PubMed  CAS  Google Scholar 

  • Ding S-L (2013) Comparative anatomy of the prosubiculum, subiculum, presubiculum, postsubiculum, and parasubiculum in human, monkey, and rodent. J Comp Neurol 521:4145–4162

    Article  PubMed  Google Scholar 

  • Ego-Stengel V, Wilson MA (2010) Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20:1–10

    PubMed  PubMed Central  Google Scholar 

  • Eller J, Zarnadze S, Peter Bäuerle P, Dugladze T, Gloveli T (2015) Cell type-specific separation of Subicular principal neurons during network activities. PLoS One. https://doi.org/10.1371/journal.pone.0123636

  • Geva-Sagiv M, Romani S, Las L, Ulanovsky N (2016) Hippocampal global remapping for different sensory modalities in flying bats. Nat Neurosci 19:952–958

    Article  PubMed  CAS  Google Scholar 

  • Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB (2009) Selective suppression of hippocampal ripples impairs spatial memory. Nat Neurosci 12:1222–1223

    Article  PubMed  CAS  Google Scholar 

  • Graves AR, Moore S, Bloss EB, Mensh BD, Kath WK, Spruston N (2012) Hippocampal pyramidal neurons comprise two distinct cell types that are countermodulated by metabotropic receptors. Neuron 76:776–789

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Greene JR, Mason A (1996) Neuronal diversity in the subiculum: correlations with the effects of somatostatin on intrinsic properties and on GABA-mediated IPSPs in vitro. J Neurophysiol 76:1657–1666

    Article  PubMed  CAS  Google Scholar 

  • Harris KD, Shepherd GMG (2015) The neocortical circuit: themes and variations. Nat Neurosci 18:170–181

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hulse BK, Moreaux LC, Lubenov EV, Siapas AG (2016) Membrane potential dynamics of CA1 pyramidal neurons during hippocampal ripples in awake mice. Neuron 89:800–813

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jadhav SP, Kemere C, German PW, Frank LM (2012) Awake hippocampal sharp-wave ripples support spatial memory. Science 336:1454–1458

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10:100–107

    Article  PubMed  CAS  Google Scholar 

  • Jung HY, Staff NP, Spruston N (2001) Action potential bursting in subicular pyramidal neurons is driven by a calcium tail current. J Neurosci 21:3312–3321

    Article  PubMed  CAS  Google Scholar 

  • Karlsson MP, Frank LM (2009) Awake replay of remote experiences in the hippocampus. Nat Neurosci 12:913–918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawaguchi Y, Hama K (1987) Fast-spiking non-pyramidal cells in the hippocampal CA3 region, dentate gyrus and subiculum of rats. Brain Res 425:351–355

    Article  PubMed  CAS  Google Scholar 

  • Kim Y, Spruston N (2012) Target-specific output patterns are predicted by the distribution of regular-spiking and bursting pyramidal neurons in the subiculum. Hippocampus 22:693–706

    Article  PubMed  Google Scholar 

  • Kim SM, Ganguli S, Frank LM (2012) Spatial information outflow from the hippocampal circuit: distributed spatial coding and phase precession in the subiculum. J Neurosci 32:11539–11558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kintscher M, Breustedt J, Miceli S, Schmitz D, Wozny C (2012) Group II metabotropic glutamate receptors depress synaptic transmission onto subicular burst firing neurons. PLoS One. https://doi.org/10.1371/journal.pone.0045039

  • Kloosterman F, Witter MP, Van Haeften T (2003) Topographical and laminar organization of subicular projections to the parahippocampal region of the rat. J Comp Neurol 455:156–171

    Article  PubMed  Google Scholar 

  • Köhler C, Schultzberg M, Radesäter AC (1987) Distribution of neuropeptide Y receptors in the rat hippocampal region. Neurosci Lett 75:141–146

    Article  PubMed  Google Scholar 

  • Korte M, Schmitz D (2016) Cellular and system biology of memory: timing, molecules, and beyond. Physiol Rev 96:647–693

    Article  PubMed  CAS  Google Scholar 

  • Kosel KC, Van Hoesen GW, Rosene DL (1983) A direct projection from the perirhinal cortex (area 35) to the subiculum in the rat. Brain Res 269:347–351

    Article  PubMed  CAS  Google Scholar 

  • Krook-Magnuson E, Varga C, Lee S-H, Soltesz I (2012) New dimensions of interneuronal specialization unmasked by principal cell heterogeneity. Trends Neurosci 35:175–184

    Article  PubMed  CAS  Google Scholar 

  • Lee AK, Wilson MA (2002) Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36:1183–1194

    Article  PubMed  CAS  Google Scholar 

  • Lee S-H, Marchionni I, Bezaire M, Varga C, Danielson N, Lovett-Barron M, Losonczy A, Soltesz I (2014) Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells. Neuron 82:1129–1144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lever C, Burton S, Jeewajee A, O'Keefe J, Burgess N (2009) Boundary vector cells in the subiculum of the hippocampal formation. J Neurosci 29:9771–9777

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lisman JE (1997) Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci 20:38–43

    Article  PubMed  CAS  Google Scholar 

  • Naber PA, Witter MP (1998) Subicular efferents are organized mostly as parallel projections: a double-labeling, retrograde-tracing study in the rat. J Comp Neurol 393:284–297

    Article  PubMed  CAS  Google Scholar 

  • Naber PA, Witter MP, Silva FHL (2000) Networks of the hippocampal memory system of the rat. The pivotal role of the subiculum. Ann N Y Acad Sci 911:392–403

    Article  PubMed  CAS  Google Scholar 

  • Namura S, Takada M, Kikuchi H, Mizuno N (1994) Topographical organization of subicular neurons projecting to subcortical regions. Brain Res Bull 35(3):221–231

    Article  PubMed  CAS  Google Scholar 

  • O’Keefe J, Nadel L (1978) The Hippocampus as a cognitive map. S.L. Oxford University Press

  • Olson JM, Tongprasearth K, Nitz DA (2017) Subiculum neurons map the current axis of travel. Nat Neurosci 20:170–172

    Article  PubMed  CAS  Google Scholar 

  • Packer AM, Yuste R (2011) Dense, unspecific connectivity of neocortical parvalbumin-positive interneurons: a canonical microcircuit for inhibition? J Neurosci 31:13260–13271

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pandey A, Sikdar SK (2014) Depression biased non-Hebbian spike-timing-dependent synaptic plasticity in the rat subiculum. J Physiol 592:3537–3557

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peng Y, Tomás B, Federico J, Klisch C, Vida I, Geiger JRP (2017) Layer-specific organization of local excitatory and inhibitory synaptic connectivity in the rat presubiculum. Cereb Cortex 27:2435–2452

    Article  PubMed  PubMed Central  Google Scholar 

  • Pitkänen A, Pikkarainen M, Nurminen N, Ylinen A (2000) Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat: a review. Ann N Y Acad Sci 911:369–391

    Article  PubMed  Google Scholar 

  • Roy DS, Kitamura T, Okuyama T, Ogawa SK, Sun C, Obata Y, Yoshiki A, Tonegawa S (2017) Distinct neural circuits for the formation and retrieval of episodic memories. Cell 170:1000–1012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schlingloff D, Káli S, Freund TF, Hájos N, Gulyás AI (2014) Mechanisms of sharp wave initiation and ripple generation. J Neurosci 34:11385–11398

    Article  PubMed  CAS  Google Scholar 

  • Sharp PE (2006) Subicular place cells generate the same “map” for different environments: comparison with hippocampal cells. Behav Brain Res 174:206–214

    Article  PubMed  CAS  Google Scholar 

  • Sharp PE, Green C (1994) Spatial correlates of firing patterns of single cells in the subiculum of the freely moving rat. J Neurosci 14:2339–2356

    Article  PubMed  CAS  Google Scholar 

  • Staff NP, Jung HY, Thiagarajan T, Yao M, Spruston N (2000) Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus. J Neurophysiol 84:2398–2408

    Article  PubMed  CAS  Google Scholar 

  • Stewart M (1997) Antidromic and orthodromic responses by subicular neurons in rat brain slices. Brain Res 769:71–85

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Nguyen AQ, Nguyen JP, Le L, Saur D, Choi J, Callaway EM, Xu X (2014) Cell-type-specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing. Cell Rep 7:269–280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tsao A, Moser M-B, Moser EI (2013) Traces of experience in the lateral entorhinal cortex. Curr Biol 23:399–405

    Article  PubMed  CAS  Google Scholar 

  • Valero M, Cid E, Averkin RG, Aguilar J, Sanchez-Aguilera A, Viney TJ, Gomez-Dominguez D, Bellistri E, de la Prida LM (2015) Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples. Nat Neurosci 18:1281–1290

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wilson MA, McNaughton BL (1994) Reactivation of hippocampal ensemble memories during sleep. Science 265:676–679

    Article  PubMed  CAS  Google Scholar 

  • Winterer J, Maier N, Wozny C, Beed P, Breustedt J, Evangelista R, Peng Y, D'Albis T, Kempter R, Schmitz D (2017) Excitatory microcircuits within superficial layers of the medial entorhinal cortex. Cell Rep 19:1110–1116

    Article  PubMed  CAS  Google Scholar 

  • Witter MP (2006) Connections of the subiculum of the rat: topography in relation to columnar and laminar organization. Behav Brain Res 174:251–264

    Article  PubMed  CAS  Google Scholar 

  • Witter MP, Amaral DG (1991) Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex. J Comp Neurol 307:437–459

    Article  PubMed  CAS  Google Scholar 

  • Witter MP, Groenewegen HJ, da Silva FHL, Lohman AH (1989) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog Neurobiol 33:161–253

    Article  PubMed  CAS  Google Scholar 

  • Witter MP, Ostendorf RH, Groenewegen HJ (1990) Heterogeneity in the dorsal subiculum of the rat. Distinct neuronal zones project to different cortical and subcortical targets. Eur J Neurosci 2:718–725

    Article  PubMed  Google Scholar 

  • Wozny C, Maier N, Fidzinski P, Breustedt J, Behr J, Schmitz D (2008a) Differential cAMP signaling at hippocampal output synapses. J Neurosci 28:14358–14362

    Article  PubMed  CAS  Google Scholar 

  • Wozny C, Maier N, Schmitz D, Behr J (2008b) Two different forms of long-term potentiation at CA1-subiculum synapses. J Physiol 586:2725–2734

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wright NF, Erichsen JT, Vann SD, O’Mara SM, Aggleton JP (2010) Parallel but separate inputs from limbic cortices to the mammillary bodies and anterior thalamic nuclei in the rat. J Comp Neurol 518:2334–2354

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu X, Sun Y, Holmes TC, López AJ (2016) Noncanonical connections between the subiculum and hippocampal CA1. J Comp Neurol 524:3666–3673

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Noam Nitzan for critical comments on the manuscript.

Funding

Funding for this work has been received from Deutsche Forschungsgemeinschaft (SFB 958, Exc 257 and KE 788/3-1, Research Unit Interneuron Synaptic Plasticity FOR 2143 and Research Training Groups GRK 1123 and GRK 1589), the Bernstein Center for Computational Neuroscience Berlin (01GQ1001A), Bernstein Focus Learning (01GQ0972) and BMBF (SMARTAGE).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudia Böhm.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Böhm, C., Peng, Y., Geiger, J.R.P. et al. Routes to, from and within the subiculum. Cell Tissue Res 373, 557–563 (2018). https://doi.org/10.1007/s00441-018-2848-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2848-4

Keywords

Navigation