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MeSH Review

Perforant Pathway

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Disease relevance of Perforant Pathway


Psychiatry related information on Perforant Pathway


High impact information on Perforant Pathway


Chemical compound and disease context of Perforant Pathway


Biological context of Perforant Pathway


Anatomical context of Perforant Pathway


Associations of Perforant Pathway with chemical compounds

  • Glutamate as transmitter of hippocampal perforant path [28].
  • Electrophysiological recordings from dentate granule cells revealed that high-frequency stimulation of perforant path afferents induced a robust STP and LTP of both (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic responses [29].
  • Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells [30].
  • Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration [31].
  • After chronic TMS, FFA was ineffective in enhancing reactivity to perforant path stimulation, probably because it lost the ability to release serotonin [32].

Gene context of Perforant Pathway

  • Within resistant sectors, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular layer of the dentate gyrus and in the stratum lucidum of CA3 (i.e., the termination zones of perforant pathway and mossy fibers) [33].
  • Thus, neprilysin was decreased selectively at the terminal zones and on axons of the lateral perforant path and the mossy fibers [34].
  • Perforant pathway stimulation for 24 hours, which evoked population spikes and epileptiform discharges in both dentate granule cells and hippocampal pyramidal neurons, induced GAD65-, GAD67-, and GABA-LI only in granule cells [35].
  • These values probably reflect enhanced synthesis since the largest increases were seen in subregions (dentate gyrus, hilus/CA4, CA3) that contain perforant path terminals, and where previously observed intrinsic hippocampal thyrotropin-releasing hormone messenger RNA increases were seen [36].
  • Furthermore, although brief high-frequency stimulation of the perforant path produced robust long-term potentiation (LTP) of synaptic responses in the dentate gyrus of +/+ mice, LTP was attenuated in Cm /+ mice [37].

Analytical, diagnostic and therapeutic context of Perforant Pathway


  1. Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Liu, H., Mazarati, A.M., Katsumori, H., Sankar, R., Wasterlain, C.G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Increased expression of microtubule-associated protein 1B in the hippocampus, subiculum, and perforant path of rats treated with a high dose of pentylenetetrazole. Popa-Wagner, A., Fischer, B., Schmoll, H., Platt, D., Kessler, C. Exp. Neurol. (1997) [Pubmed]
  3. Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study. Crain, B.J., Westerkam, W.D., Harrison, A.H., Nadler, J.V. Neuroscience (1988) [Pubmed]
  4. Induction of Fos in glia-like cells after focal brain injury but not during wallerian degeneration. Dragunow, M., de Castro, D., Faull, R.L. Brain Res. (1990) [Pubmed]
  5. Alzheimer's disease: glutamate depletion in the hippocampal perforant pathway zone. Hyman, B.T., Van Hoesen, G.W., Damasio, A.R. Ann. Neurol. (1987) [Pubmed]
  6. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. Albiston, A.L., McDowall, S.G., Matsacos, D., Sim, P., Clune, E., Mustafa, T., Lee, J., Mendelsohn, F.A., Simpson, R.J., Connolly, L.M., Chai, S.Y. J. Biol. Chem. (2001) [Pubmed]
  7. Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Thal, D.R., Holzer, M., Rüb, U., Waldmann, G., Günzel, S., Zedlick, D., Schober, R. Exp. Neurol. (2000) [Pubmed]
  8. Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Williams, J.H., Errington, M.L., Lynch, M.A., Bliss, T.V. Nature (1989) [Pubmed]
  9. Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression. Abraham, W.C., Goddard, G.V. Nature (1983) [Pubmed]
  10. Long-term potentiation of the perforant path in vivo is associated with increased glutamate release. Dolphin, A.C., Errington, M.L., Bliss, T.V. Nature (1982) [Pubmed]
  11. Entorhinal-hippocampal connections: a speculative view of their function. Jones, R.S. Trends Neurosci. (1993) [Pubmed]
  12. Up regulation of calbindin-D28K mRNA in the rat hippocampus following focal stimulation of the perforant path. Lowenstein, D.H., Miles, M.F., Hatam, F., McCabe, T. Neuron (1991) [Pubmed]
  13. Modulation of hippocampal excitability and seizures by galanin. Mazarati, A.M., Hohmann, J.G., Bacon, A., Liu, H., Sankar, R., Steiner, R.A., Wynick, D., Wasterlain, C.G. J. Neurosci. (2000) [Pubmed]
  14. Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling. Haas, K.Z., Sperber, E.F., Opanashuk, L.A., Stanton, P.K., Moshé, S.L. Hippocampus. (2001) [Pubmed]
  15. Perforant path activation of ectopic granule cells that are born after pilocarpine-induced seizures. Scharfman, H.E., Sollas, A.E., Berger, R.E., Goodman, J.H., Pierce, J.P. Neuroscience (2003) [Pubmed]
  16. Status epilepticus causes selective regional damage and loss of GABAergic neurons in the rat amygdaloid complex. Tuunanen, J., Halonen, T., Pitkänen, A. Eur. J. Neurosci. (1996) [Pubmed]
  17. Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Mazarati, A.M., Baldwin, R.A., Sankar, R., Wasterlain, C.G. Brain Res. (1998) [Pubmed]
  18. Type 4a metabotropic glutamate receptor: identification of new potent agonists and differentiation from the L-(+)-2-amino-4-phosphonobutanoic acid-sensitive receptor in the lateral perforant pathway in rats. Johansen, P.A., Chase, L.A., Sinor, A.D., Koerner, J.F., Johnson, R.L., Robinson, M.B. Mol. Pharmacol. (1995) [Pubmed]
  19. Characterization in vivo of the NMDA receptor-mediated component of dentate granule cell population synaptic responses to perforant path input. Blanpied, T.A., Berger, T.W. Hippocampus. (1992) [Pubmed]
  20. Low chloride-dependent release of taurine by a furosemide-sensitive process in the in vivo rat hippocampus. Solis, J.M., Herranz, A.S., Herreras, O., Lerma, J., Martin Del Rio, R. Neuroscience (1988) [Pubmed]
  21. Positive feedback from hilar mossy cells to granule cells in the dentate gyrus revealed by voltage-sensitive dye and microelectrode recording. Jackson, M.B., Scharfman, H.E. J. Neurophysiol. (1996) [Pubmed]
  22. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain. Ramos-Moreno, T., Galazo, M.J., Porrero, C., Martínez-Cerdeño, V., Clascá, F. Eur. J. Neurosci. (2006) [Pubmed]
  23. Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. Ylinen, A.M., Miettinen, R., Pitkänen, A., Gulyas, A.I., Freund, T.F., Riekkinen, P.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Control of sensory activation of granule cells in the fascia dentata by extrinsic afferents: septal and entorhinal inputs. Foster, T.C., Hampson, R.E., West, M.O., Deadwyler, S.A. J. Neurosci. (1988) [Pubmed]
  25. Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence. Cavazos, J.E., Golarai, G., Sutula, T.P. J. Neurosci. (1991) [Pubmed]
  26. Type I adenylyl cyclase mutant mice have impaired mossy fiber long-term potentiation. Villacres, E.C., Wong, S.T., Chavkin, C., Storm, D.R. J. Neurosci. (1998) [Pubmed]
  27. Enhancement of long-term potentiation by cis-unsaturated fatty acid: relation to protein kinase C and phospholipase A2. Linden, D.J., Sheu, F.S., Murakami, K., Routtenberg, A. J. Neurosci. (1987) [Pubmed]
  28. Glutamate as transmitter of hippocampal perforant path. White, W.F., Nadler, J.V., Hamberger, A., Cotman, C.W., Cummins, J.T. Nature (1977) [Pubmed]
  29. Novel expression mechanism for synaptic potentiation: alignment of presynaptic release site and postsynaptic receptor. Xie, X., Liaw, J.S., Baudry, M., Berger, T.W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  30. Adenosine decreases neurotransmitter release at central synapses. Prince, D.A., Stevens, C.F. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  31. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. Parent, J.M., Yu, T.W., Leibowitz, R.T., Geschwind, D.H., Sloviter, R.S., Lowenstein, D.H. J. Neurosci. (1997) [Pubmed]
  32. Long-term effects of transcranial magnetic stimulation on hippocampal reactivity to afferent stimulation. Levkovitz, Y., Marx, J., Grisaru, N., Segal, M. J. Neurosci. (1999) [Pubmed]
  33. AMPA-selective glutamate receptor subtype immunoreactivity in the hippocampal formation of patients with Alzheimer's disease. Ikonomovic, M.D., Sheffield, R., Armstrong, D.M. Hippocampus. (1995) [Pubmed]
  34. Region-specific reduction of A beta-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging. Iwata, N., Takaki, Y., Fukami, S., Tsubuki, S., Saido, T.C. J. Neurosci. Res. (2002) [Pubmed]
  35. Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. Sloviter, R.S., Dichter, M.A., Rachinsky, T.L., Dean, E., Goodman, J.H., Sollas, A.L., Martin, D.L. J. Comp. Neurol. (1996) [Pubmed]
  36. Changes in thyrotropin-releasing hormone levels in hippocampal subregions induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling. Knoblach, S.M., Kubek, M.J. Neuroscience (1997) [Pubmed]
  37. Coloboma contiguous gene deletion encompassing Snap alters hippocampal plasticity. Steffensen, S.C., Wilson, M.C., Henriksen, S.J. Synapse (1996) [Pubmed]
  38. Postsynaptic factors in the expression of long-term potentiation (LTP): increased glutamate receptor binding following LTP induction in vivo. Maren, S., Tocco, G., Standley, S., Baudry, M., Thompson, R.F. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  39. Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection. Gazzaley, A.H., Benson, D.L., Huntley, G.W., Morrison, J.H. J. Neurosci. (1997) [Pubmed]
  40. Ascorbate and glutamate release in the rat hippocampus after perforant path stimulation: a "dialysis electrode" study. Walker, M.C., Galley, P.T., Errington, M.L., Shorvon, S.D., Jefferys, J.G. J. Neurochem. (1995) [Pubmed]
  41. Changes in protein kinase C isozymes in the rat hippocampal formation following hippocampal lesion. Shimohama, S., Saitoh, T., Gage, F.H. Hippocampus. (1993) [Pubmed]
  42. Halothane as a neuroprotectant during constant stimulation of the perforant path. Walker, M.C., Perry, H., Scaravilli, F., Patsalos, P.N., Shorvon, S.D., Jefferys, J.G. Epilepsia (1999) [Pubmed]
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