Skip to main content
SpringerLink
Log in

Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal area: a tracing study in the rat

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Neurons in layer III of the medial entorhinal area (MEA) in the rat are extremely vulnerable to local injections of amino-oxyacetic acid and to exprimentally induced limbic seizures. A comparable specific pathology has been noted in surgical specimens from patients with temporal lobe epilepsy. Efforts to understand this preferential neuronal vulnerability led us to study the neural input to this layer in the rat. Iontophoretic injection of the retrograde tracer fast blue, aimed at layer III of the MEA, resulted in retrogradely labeled neurons in the presubiculum in all the injected hemispheres. The nucleus reuniens thalami, the anteromedial thalamic nucleus, the ventral portion of the claustrum (endopiriform nucleus), the dorsomedial parts of the anteroventral thalamic nucleus, and the septum-diagonal band complex were labeled less frequently. In only one experiment, retrogradely labeled neurons were observed in the ventrolateral hypothalamus and in the brainstem nucleus raphe dorsalis. Since projections from claustrum to the entorhinal cortex has not been studied in the rat with modern sensitive anterograde tracing techniques, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were placed into the ventral portion of the claustrum. Anterogradely labeled fibers in the entorhinal area proved not to be confined to the MEA, since a prominent projection distributed to the lateral entorhinal area as well. In both areas, the densest terminal labeling was present in layers IV–VI, whereas layer III appeared to be only sparsely labeled. The present data indicate that of all potential afferents only those from the presubiculum distribute preferentially to layer III of the MEA. This, in turn, suggests a potentially important role of the presubiculum in the seizure-related degeneration of neurons in layer III of the MEA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alonso A, Köhler C (1984) A study of the reciprocal connections between the septum and the entorhinal area using anterograde and retrograde axonal transport methods in the rat brain. J Comp Neurol 225:327–342

    Google Scholar 

  • Bartesaghi R, Gessi T, Migliore M (1995) Input-output relations in the entorhinal-hippocampal-entorhinal loop: entorhinal cortex and dentate gyrus. Hippocampus 5:440–451

    Google Scholar 

  • Beckstead RM (1978) Afferent connections of the entorhinal area in the rat as demonstrated by retrograde cell-labeling with horseradish peroxidase. Brain Res 152:249–264

    Google Scholar 

  • Bekenstein JW, Lothman EW (1993) Dormancy of inhibitory interneurons in a model of temporal lobe epilepsy. Science 259:97–100

    Google Scholar 

  • Biziere K, Coyle JT (1978) Influence of cortico-striatal afferents on striatal kainic acid neurotoxicity. Neurosci Lett 8:303–310

    Google Scholar 

  • Blackstad TW (1956) Commissural connections of the hippocampal region in the rat, with special reference to their mode of termination. J Comp Neurol 105:417–537

    Google Scholar 

  • Caballero-Bleda M, Witter MP (1993) Regional and laminar organization of projections from the presubiculum and parasubiculum to the entorhinal cortex: an anterograde tracing study in the rat. J Comp Neurol 328:115–129

    Google Scholar 

  • Cabellero-Bleda M, Witter MP (1994) Projections from the presubiculum and the parasubiculum to morphologically characterized entorhinal-hippocampal projection neurons in the rat. Exp Brain Res 101:93–108

    Google Scholar 

  • Canteras NS, Simerly RB, Swanson LW (1994) Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol 348:41–79

    Google Scholar 

  • Clifford DB, Olney JW, Benz AM, Fuller TA, Zoruski CF (1990) Ketamine, phencyclidine, and MK-801 protect against kainic acid-induced seizure-related brain damage. Epilepsia 31:382–390

    CAS  PubMed  Google Scholar 

  • Collins RC, Tearse RG, Lothman EW (1983) Functional anatomy of limbic seizures: focal discharges from medial entorhinal cortex in rat. Brain Res 280:25–40

    Google Scholar 

  • Colonnier M (1968) Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study. Brain Res 9:268–287

    Google Scholar 

  • Cross AJ, Jones JA, Baldwin HA, Green AR (1991) Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. Br J Pharmacol 104:406–411

    Google Scholar 

  • Du F, Schwarcz R (1992) Aminooxyacetic acid causes selective neuronal loss in layer III of the rat medial entorhinal cortex. Neurosci Lett 147:185–188

    Google Scholar 

  • Du F, Whetsell WO Jr, Abou-Khalil B, Blumenkopf B, Lothman EW, Schwarcz R (1993) Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Epilepsy Res 16:223–233

    Google Scholar 

  • Du F, Eid T, Lothman EW, Köhler C, Schwarcz R (1995) Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. J Neurosci 15:8301–8313

    Google Scholar 

  • During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizures in the conscious human brain. Lancet 341:1607–1611

    Google Scholar 

  • Eid T, Du F, Schwarcz R (1995) Differential neuronal vulnerability to aminooxyacetic acid and quinolinic acid in the rat parahippocampal region. Neuroscience 68:645–656

    Google Scholar 

  • Gastaut H (1956) Colloque sur les problemes d'anatomie normale et pathologique poses par les decharges epileptiques. Acta Med Belg 5–66

  • Gaykema RPA, Luiten PGM, Nyakas C, Traber J (1990) Cortical projection patterns of the medial septum-diagonal band complex. J Comp Neurol 293:103–124

    Google Scholar 

  • Haug FMS (1976) Sulphide silver pattern and cytoarchitectonics of parahippocampal areas in the rat. Special reference to the subdivision of area entorhinalis (area 28) and its demarcation from the pyriform cortex. Adv Anat Embryol Cell Biol 52:1–73

    Google Scholar 

  • Haeften T van, Wouterlood FG, Jorritsma-Byham B, Witter MP (1995) Light-and electron-microscopic demonstration of a presubicular GABAergic projection to the medial entorhinal cortex of the rat (abstract). Eur J Neurosci [Suppl] 8:153

    Google Scholar 

  • Johansen FF, Diemer NH (1991) Enhancement of GABA neurotransmission after cerebral ischemia in the rat reduces loss of hippocampal CA1 pyramidal cells. Acta Neurol Scand 84:1–6

    Google Scholar 

  • Jones RSG (1993) Entorhinal-hippocampal connections: a speculative view of their function. Trends Neurosci 16:58–64

    Google Scholar 

  • Köhler C (1985) Intrinsic projections of the retrohippocampal region in the rat brain. I. The subicular complex. J Comp Neurol 236:504–522

    Google Scholar 

  • Köhler C (1986) Intrinsic connections of the retrohippocampal region in the rat brain. II. The medial entorhinal area. J Comp Neurol 246:149–169

    Google Scholar 

  • Köhler C, Schwarcz R, Fuxe K (1978) Perforant path transections protect hippocampal granule cells from kainate lesion. Neurosci Lett 10:241–246

    Google Scholar 

  • Krettek JE, Price JL (1977) Projections from the amyglaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat. J Comp Neurol 172:723–752

    Google Scholar 

  • McGeer EG, McGeer PL, Singh K (1978) Kainate-induced degeneration of neostriatal neurons: dependency upon corticostriatal tract. Brain Res 139:381–383

    Google Scholar 

  • Meldrum BS (1995) Neurotransmission in epilepsy. Epilepsia 36:S30-S35

    Google Scholar 

  • Nadler JV, Cuthbertson GJ (1980) Kainic acid neurotoxicity toard hippocampal formation: dependence on specific excitatory pathways. Brain Res 195:47–56

    Google Scholar 

  • Olney JW, Collins RC, Sloviter RS (1986) Excitotoxic mechanisms of epileptic brain damage. Adv Neurol 44:857–877

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, San Diego, CA

    Google Scholar 

  • Ramón y Cajal S (1911) Histologie du systeme nerveux de l'homme et des vertebrés. Maloine, Paris

    Google Scholar 

  • Raviola G, Raviola E (1967) Light and electron-microscopic observations on the inner plexiform layer of the rabbit retina. Am J Anat 120:403–426

    Google Scholar 

  • Risold PY, Canteras NS, Swanson LW (1994) Organization of projections from the anterior hypothalamic nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol 348:1–40

    Google Scholar 

  • Rutecki PA, Grossman RG, Armstrong D, Irish-Loewen S (1989) Electrophysiological connections between the hippocampus and entorhinal cortex in patients with complex partial seizures. J Neurosurg 70:667–675

    Google Scholar 

  • Ruth RE, Collier TJ, Routtenberg A (1982) Topography between the entorhinal cortex and the dentate septotemporal axis in rats. I. Medial and intermediate entorhinal projecting cells. J Comp Neurol 209:69–78

    Google Scholar 

  • Ruth RE, Collier TJ, Routtenberg A (1988) Topographical relationship between the entorhinal cortex and the septotemporal axis of the dentate gyrus in rats. II. Cells projecting from lateral entorhinal subdivisions. J Comp Neurol 270:506–516

    Google Scholar 

  • Segal M (1977) Afferents to the entorhinal cortex of the rat studied by the method of retrograde transport of horseradish peroxidase. Exp Neurol 57:750–765

    Google Scholar 

  • Sloviter RS (1991) Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the “dormant basket cell” hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus 1:41–66

    Google Scholar 

  • Spencer SS, Spencer DD (1994) Entorhinal-hippocampal interactions in medial temporal lobe epilepsy. Epilepsia 35:721–727

    Google Scholar 

  • Steward O (1976) Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat. J Comp Neurol 167:285–314

    Google Scholar 

  • Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. J Comp Neurol 169:347–370

    Google Scholar 

  • Swanson LW, Köhler C, Björklund A (1987) The limbic region. I. The septohippocampal system. In: Björklund A, Hökfelt T, Swanson LW (eds) (Handbook of chemical neuroanatomy, vol 5) Integrated systems of the CNS, part I. Elsevier, Amsterdam, pp 125–227

    Google Scholar 

  • ]Uchizono K (1965) Characteristics of excitatory and inhibitory synapses in the central nervous system of the cat. Nature 207:642–643

    Google Scholar 

  • Vertes RP (1991) A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol 313:643–668

    Google Scholar 

  • Vertes RP (1992) PHA-L analysis of projections from the supramammillary nucleus in the rat. J Comp Neurol 326:595–622

    Google Scholar 

  • Witter MP, Room P, Groenewegen HJ, Lohman AHM (1986) Reciprocal connections of the insular and piriform claustrum with limbic cortex: an anatomical study in the cat. Neuroscience 24:519–539

    Google Scholar 

  • Witter MP, Griffioen AW, Jorritsma-Byham B, Krijnen JLM (1988) Entorhinal projections to the hippocampal CA1 region in the rat: an underestimated pathway. Neurosci Lett 85:193–198

    Google Scholar 

  • Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AHM (1989a) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Progr Neurobiol 33:161–253

    Google Scholar 

  • Witter MP, Van Hoesen GW, Amaral DG (1989b) Topographical organization of the entorhinal projection to the dentate gyrus of the monkey. J Neurosci 9:216–228

    Google Scholar 

  • Witter MP, Eid T, Schwarcz R (1994) Anatomical analysis of afferent connections of layer III of the medial entorhinal cortex in the rat. Soc Neurosci Abstr 20:151. 15

    Google Scholar 

  • Wouterlood FG, Saldana E, Witter MP (1990) Projection from the nucleus reiniens thalami to the hippocampal region: light and electron microscopic tracing study in the rat with the anterograde tracer Phaseolus vulgaris-leucoagglutinin. J Comp Neurol 296:179–203

    Google Scholar 

  • Wouterlood FG, Haeften T van, Witter MP (1995) Demonstration of a presubicular GABAergic projection to the medial entorhinal cortex of the rat. Soc Neurosci Abstr 21:428

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA

    T. Eid & R. Schwarcz

  2. Graduate School Neurosciences Amsterdam, Department of Anatomy and Embryology, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, NL-1081, BT Amsterdam, The Netherlands

    B. Jorritsma-Byham & M. P. Witter

  3. Department of Anatomy and Cell Biology, University of Bergen, Bergen, Norway

    T. Eid

Authors
  1. T. Eid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Jorritsma-Byham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Schwarcz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. P. Witter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eid, T., Jorritsma-Byham, B., Schwarcz, R. et al. Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal area: a tracing study in the rat. Exp Brain Res 109, 209–218 (1996). https://doi.org/10.1007/BF00231782

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00231782

Key words

Search

Navigation