In rodent models for neuropsychiatric disorders reduced number of hippocampal interneurons have been reported, but the total number of GABAergic neurons in the normal rat hippocampus is yet unknown. We used in situ hybridization method to label the 65 isoform of glutamic acid decarboxylase (GAD65) and counted the number of GAD65 mRNA-expressing neurons along the entire septo-temporal axis of the hippocampus. We found that 2/3 of the interneurons were in Ammon’s horn (61,590) and 1/3 in the dentate gyrus (28,000). We observed the following numbers in Ammon’s horn: CA3 area 33,400, CA2 area 4,190, CA1 area 24,000 and in the dentate gyrus: 6,000 in the molecular and 9,000 in the granule cell layers and 13,000 in the hilus. GAD65 mRNA-expressing neurons were significantly more numerous in dorsal than in ventral hippocampus. The ratio between interneurons and principal cells was lowest in the granule cell layer (0.9%) and highest in hilus (21%). In Ammon’s horn this ratio was constant being 13% in CA3 and 8% in CA1-2 areas. In the entire hippocampal formation, the interneuron/principal cell ratio was 6%, with a significant difference between Ammon’s horn (9.5%) and the dentate gyrus (2.8%) including the hilus. Such low ratios could suggest that even a limited loss of GABAergic neurons in the hippocampus may have a considerable functional impact.
Amaral, D. G., Witter, M. P. (1989) The three dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571–591.
Witter M. P. , 'The three dimensional organization of the hippocampal formation: a review of anatomical data ' (1989 ) 31 Neuroscience : 571 -591 .
Aika, Y., Ren, J. Q., Kosaka, K., Kosaka, T. (1994) Quantitative analysis of GABA-likeimmunoreactive and parvalbumine-containing neurons in the CA1 region of the rat hippocampus using a stereological method, the disector. Exp. Brain Res. 99, 267–276.
Kosaka T. , 'Quantitative analysis of GABA-likeimmunoreactive and parvalbumine-containing neurons in the CA1 region of the rat hippocampus using a stereological method, the disector ' (1994 ) 99 Exp. Brain Res. : 267 -276 .
Beaulieu, C. (1993) Numerical data on neocortical neurons in adult rat, with special reference to the GABAergic population. Brain Res. 609, 284–292.
Beaulieu C. , 'Numerical data on neocortical neurons in adult rat, with special reference to the GABAergic population ' (1993 ) 609 Brain Res. : 284 -292 .
Benes, F. M., Berretta, S. (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25, 1–27.
Berretta S. , 'GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder ' (2001 ) 25 Neuropsychopharmacology : 1 -27 .
Benes, F. M., Lange, N. (2001) Two-dimensional versus three-dimensional cell counting: a practical perspective. Trends Neurosci. 24, 11–17.
Lange N. , 'Two-dimensional versus three-dimensional cell counting: a practical perspective ' (2001 ) 24 Trends Neurosci. : 11 -17 .
Boss, B. D., Peterson, G. M., Cowan, W. M. (1985) On the number of neurons in the dentate gyrus of the rat. Brain Res. 338, 144–150.
Cowan W. M. , 'On the number of neurons in the dentate gyrus of the rat ' (1985 ) 338 Brain Res. : 144 -150 .
Boss, B. D., Turlejski, K., Stanfield, B. B., Cowan, W. M. (1987) On the numbers of neurons in fields CA1 and CA3 of the hippocampus of Sprague-Dawley and Wistar rats. Brain Res. 406, 280–287.
Cowan W. M. , 'On the numbers of neurons in fields CA1 and CA3 of the hippocampus of Sprague-Dawley and Wistar rats ' (1987 ) 406 Brain Res. : 280 -287 .
Brambilla, P., Perez, J., Barale, F., Schettini, G., Soares, J. C. (2003) GABAergic dysfunction in mood disorders. Mol. Psychiatry 8, 721–737.
Soares J. C. , 'GABAergic dysfunction in mood disorders ' (2003 ) 8 Mol. Psychiatry : 721 -737 .
Buckmaster, P. S., Dudek, F. E. (1997) Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J. Comp. Neurol. 385, 385–404.
Dudek F. E. , 'Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats ' (1997 ) 385 J. Comp. Neurol. : 385 -404 .
Czéh, B., Simon, M., van der Hart, M. G., Schmelting, B., Hesselink, M. B., Fuchs, E. (2005) Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in the hippocampus: prevention by treatment with a substance P receptor (NK1) antagonist. Neuropsychopharmacology 30, 67–79.
Fuchs E. , 'Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in the hippocampus: prevention by treatment with a substance P receptor (NK1) antagonist ' (2005 ) 30 Neuropsychopharmacology : 67 -79 .
Dudek, F. E., Sutula, T. P. (2007) Epileptogenesis in the dentate gyrus: a critical perspective. Prog. Brain Res. 163, 755–773.
Sutula T. P. , 'Epileptogenesis in the dentate gyrus: a critical perspective ' (2007 ) 163 Prog. Brain Res. : 755 -773 .
Esclapez, M., Tillakaratne, N. J., Tobin, A. J., Houser, C. R. (1993) Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J. Comp. Neurol. 331, 339–362.
Houser C. R. , 'Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods ' (1993 ) 331 J. Comp. Neurol. : 339 -362 .
Erlander, M. G., Tillakaratne, N. J., Feldblum, S., Patel, N., Tobin, A. J. (1991) Two genes encode distinct glutamate decarboxylases. Neuron 7, 91–100.
Tobin A. J. , 'Two genes encode distinct glutamate decarboxylases ' (1991 ) 7 Neuron : 91 -100 .
Fanselow, M. S., Dong, H. W. (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65, 7–19.
Dong H. W. , 'Are the dorsal and ventral hippocampus functionally distinct structures ' (2010 ) 65 Neuron : 7 -19 .
Freund, T. F., Buzsáki, G. (1996) Interneurons of the hippocampus. Hippocampus 6, 347–470.
Buzsáki G. , 'Interneurons of the hippocampus ' (1996 ) 6 Hippocampus : 347 -470 .
Gabbott, P. L., Somogyi, P. (1986) Quantitative distribution of GABA-immunoreactive neurons in the visual cortex (area17) of the cat. Exp. Brain Res. 61, 323–331.
Somogyi P. , 'Quantitative distribution of GABA-immunoreactive neurons in the visual cortex (area17) of the cat ' (1986 ) 61 Exp. Brain Res. : 323 -331 .
Gómez-Urquijo, S. M., Reblet, C., Bueno-Lopez, J. L. (2000) GABAergic neurons in the rabbit visual cortex: percentage, layer distribution and cortical projections. Brain Res. 862, 171–179.
Bueno-Lopez J. L. , 'GABAergic neurons in the rabbit visual cortex: percentage, layer distribution and cortical projections ' (2000 ) 862 Brain Res. : 171 -179 .
Halasy, K., Somogyi, P. (1993) Subdivisions in the multiple GABAergic innervation of granule cells in the dentate gyrus of the rat hippocampus. Europ. J. Neuroscience 5, 411–429.
Somogyi P. , 'Subdivisions in the multiple GABAergic innervation of granule cells in the dentate gyrus of the rat hippocampus ' (1993 ) 5 Europ. J. Neuroscience : 411 -429 .
Houser, C. R. (2007) Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity. Prog. Brain Res. 163, 217–232.
Houser C. R. , 'Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity ' (2007 ) 163 Prog. Brain Res. : 217 -232 .
Houser, C. R., Esclapez, M. (1994) Localization of mRNAs encoding two forms of glutamic acid decarboxylase in the rat hippocampal formation. Hippocampus 4, 530–545.
Esclapez M. , 'Localization of mRNAs encoding two forms of glutamic acid decarboxylase in the rat hippocampal formation ' (1994 ) 4 Hippocampus : 530 -545 .
Hu, W., Zhang, M., Czéh, B., Flügge, G., Zhang, W. (2010) Stress impairs GABAergic network function in the hippocampus by activating nongenomic glucocorticoid receptors and affecting the integrity of the parvalbumin-expressing neuronal network. Neuropsychopharmacology 35, 1693–1707.
Zhang W. , 'Stress impairs GABAergic network function in the hippocampus by activating nongenomic glucocorticoid receptors and affecting the integrity of the parvalbumin-expressing neuronal network ' (2010 ) 35 Neuropsychopharmacology : 1693 -1707 .
Klausberger, T., Somogyi, P. (2008) Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321, 53–57.
Somogyi P. , 'Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations ' (2008 ) 321 Science : 53 -57 .
Lewis, D. A., Hashimoto, T., Volk, D. W. (2005) Cortical inhibitory neurons and schizophrenia. Nat. Rev. Neurosci. 6, 312–324.
Volk D. W. , 'Cortical inhibitory neurons and schizophrenia ' (2005 ) 6 Nat. Rev. Neurosci. : 312 -324 .
Li, J., Schwark, H. D. (1994) Distribution and proportions of GABA-immunoreactive neurons in cat primary somatosensory cortex. J. Comp. Neurol. 343, 353–361.
Schwark H. D. , 'Distribution and proportions of GABA-immunoreactive neurons in cat primary somatosensory cortex ' (1994 ) 343 J. Comp. Neurol. : 353 -361 .
Lodge, D. J., Behrens, M. M., Grace, A. A. (2009) A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J. Neurosci. 29, 2344–2354.
Grace A. A. , 'A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia ' (2009 ) 29 J. Neurosci. : 2344 -2354 .
Luscher, B., Shen, Q., Sahir, N. (2011) The GABAergic deficit hypothesis of major depressive disorder. Mol. Psychiatry 16, 383–406.
Sahir N. , 'The GABAergic deficit hypothesis of major depressive disorder ' (2011 ) 16 Mol. Psychiatry : 383 -406 .
Mora, F., Segovia, G., del Arco, A. (2007) Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res. Rev. 55, 78–88.
Arco A. , 'Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain ' (2007 ) 55 Brain Res. Rev. : 78 -88 .
Müller, G. J., Møller, A., Johansen, F. F. (2001) Stereological cell counts of GABAergic neurons in rat dentate hilus following transient cerebral ischemia. Exp. Brain Res. 141, 380–388.
Johansen F. F. , 'Stereological cell counts of GABAergic neurons in rat dentate hilus following transient cerebral ischemia ' (2001 ) 141 Exp. Brain Res. : 380 -388 .
Nomura, T., Fukuda, T., Aika, Y., Heizmann, C. W., Empson, P. C., Kobayashi, T., Kosaka, T. (1997) Distribution of non-principal neurons in the rat hippocampus, with special reference to their dorsoventral difference. Brain Res. 751, 64–80.
Kosaka T. , 'Distribution of non-principal neurons in the rat hippocampus, with special reference to their dorsoventral difference ' (1997 ) 751 Brain Res. : 64 -80 .
Nomura, T., Fukuda, T., Aika, Y., Heizmann, C. W., Emson, P. C., Kobayashi, T., Kosaka, T. (1997) Laminar distribution of non-principal neurons in the rat hippocampus, with special reference to their compositional difference among layers. Brain Res. 764, 197–204.
Kosaka T. , 'Laminar distribution of non-principal neurons in the rat hippocampus, with special reference to their compositional difference among layers ' (1997 ) 764 Brain Res. : 197 -204 .
Obenaus, A., Esclapez, M., Houser, C. R. (1993) Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures. J. Neurosci. 13, 4470–4485.
Houser C. R. , 'Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures ' (1993 ) 13 J. Neurosci. : 4470 -4485 .
Olbrich, H. G., Braak, H. (1986) Prozentualer Anteil von Pyramidenzellen und Nicht-Pyramidenzellen im Sektor CA1 des menschlichen Ammonshorn. Verhaltung der Anatomischen Gesellschaft 80, Supplement: 867–868.
Braak H. , '', in Verhaltung der Anatomischen Gesellschaft 80 , (1986 ) -.
Olbrich, H. G., Braak, H. (1987) Das Verhaltnis von Pyramidenzellen und Nicht-Pyramidenzellen im Sektor CA1 des menschlichen Ammonshornes wahrend des Alterungsprocesses. Verhaltung der Anatomischen Gesellschaft 81, Supplement: 879–880.
Braak H. , '', in Verhaltung der Anatomischen Gesellschaft 81 , (1987 ) -.
Ren, J. Q., Aika, Y., Heizmann, C. W., Kosaka, T. (1992) Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with speciel reference to GABAergic neurons and parvalbumincontaining neurons. Exp. Brain Res. 92, 1–14.
Kosaka T. , 'Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with speciel reference to GABAergic neurons and parvalbumincontaining neurons ' (1992 ) 92 Exp. Brain Res. : 1 -14 .
Seress, L., Ribak, C. E. (1983) GABAergic cells in the dentate gyrus appear to be local circuit and projection neurons. Exp. Brain Res. 50, 173–182.
Ribak C. E. , 'GABAergic cells in the dentate gyrus appear to be local circuit and projection neurons ' (1983 ) 50 Exp. Brain Res. : 173 -182 .
Shetty, A. K., Hattiangady, B., Rao, M. S. (2009) Vulnerability of hippocampal GABA-ergic interneurons to kainate-induced excitotoxic injury during old age. J. Cell Mol. Med. 13, 2408–2423.
Rao M. S. , 'Vulnerability of hippocampal GABA-ergic interneurons to kainate-induced excitotoxic injury during old age ' (2009 ) 13 J. Cell Mol. Med. : 2408 -2423 .
Stanley, E. M., Fadel, J. R., Mott, D. D. (2012) Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats. Neurobiol. Aging 33, 431.e1–13.
Mott D. D. , 'Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats ' (2012 ) 33 Neurobiol. Aging : 431.e1 -13 .
West, M. J., Gundersen, H. J. G. (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J. Comp. Neurol. 296, 1–22.
Gundersen H. J. G. , 'Unbiased stereological estimation of the number of neurons in the human hippocampus ' (1990 ) 296 J. Comp. Neurol. : 1 -22 .
West, M. J., Slomianka, L., Gundersen, H. J. (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat. Rec. 231, 482–497.
Gundersen H. J. , 'Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator ' (1991 ) 231 Anat. Rec. : 482 -497 .
Woodson, W., Nitecka, L., Ben, Ari. Y. (1989) Organization of the GABAergic system in the rat hippocampal formation: a quantitative immunocytochemical study. J. Comp. Neurol. 280, 254–271.
Ben Ari. Y. , 'Organization of the GABAergic system in the rat hippocampal formation: a quantitative immunocytochemical study ' (1989 ) 280 J. Comp. Neurol. : 254 -271 .