Abstract
Over the past 15 years, postmortem studies of the corticolimbic system in subjects with bipolar disorder (BPD) have demonstrated a variety of abnormalities affecting the gamma aminobutyric acid (GABA)ergic system. Although some of the changes are similar to those seen in individuals with schizophrenia, there are pronounced differences in the regulation of complex networks of genes involved in the expression of GAD67, a key marker for functionally differentiated GABAergic interneurons. Overall, these changes vary not only according to diagnosis, but also subregion and layer, suggesting that the activity of GABA cells in complex neural circuits are differentially affected by the unique extrinsic and intrinsic inputs that they receive at different points along a circuit like the trisynaptic pathway. Our ability to understand the functional implications in terms of complex molecular changes will ultimately influence our ability to develop novel treatments for BPD.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Acsady L, Kamondi A, Sik A, Freund T, Buzsaki G (1998) GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J Neurosci 18:3386–3403
Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S, Freedman R (1998) Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull 24:189–202
Benes FM (2010) Amygdalocortical circuitry in schizophrenia: from circuits to molecules. Neuropsychopharmacology 35:239–257
Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27
Benes, Todtenkopf, Kostoulakos P (2001) Hippocampus
Benes FM, Todtenkopf MS (1999) Effect of age neuroleptics on tyrosine hydroxylase-IR in sector CA2 of schizophrenic brain. Neuroreport 10(17):3527–3530
Benes FM, Kwok EW, Vincent SL, Todtenkopf MS (1998) A reduction of nonpyramidal cells in sector CA2 of Schizophrenics and manic depressives. Biol. Psychiatry 44(2): 88–97
Benes FM, Lim B, Matzilevich D, Walsh JP, Subburaju S, Minns M (2007) Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci USA 104:10164–10169
Benes FM, Lim B, Matzilevich D, Subburaju S, Walsh JP (2008) Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars. Proc Natl Acad Sci USA 105:20935–20940
Chen S, Wang J, Siegelbaum SA (2001) Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide. J Gen Physiol 117:491–504
Cobb SR, Larkman PM, Bulters DO, Oliver L, Gill CH, Davies CH (2003) Activation of Ih is necessary for patterning of mGluR and mAChR induced network activity in the hippocampal CA3 region. Neuropharmacology 44:293–303
Dugladze T, Vida I, Tort AB, Gross A, Otahal J, Heinemann U, Kopell NJ, Gloveli T (2007) Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy. Proc Natl Acad Sci USA 104:17530–17535
Fisahn A, Contractor A, Traub RD, Buhl EH, Heinemann SF, McBain CJ (2004) Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations. J Neurosci 24:9658–9668
Gisabella B, Cunningham M, Bolshakov V, Benes FM (2009) Amygdala-dependent regulation of electrical properties of hippocampal interneurons in a model of schizophrenia. Bio. Psychiatry 65(6):464–472
Guidotti A, Auta J, Davis JM, Gerevini VD, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study (In Process Citation). Arch Gen Psychiatry 57:1061–1069
Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA (2003) Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23:6315–6326
Lauri SE, Segerstrale M, Vesikansa A, Maingret F, Mulle C, Collingridge GL, Isaac JT, Taira T (2005) Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus. J Neurosci 25:4473–4484
Lupica CR, Bell JA, Hoffman AF, Watson PL (2001) Contribution of the hyperpolarization-activated current (I(h)) to membrane potential and GABA release in hippocampal interneurons. J Neurophysiol 86:261–268
Maccaferri G, Lacaille JC (2003) Interneuron diversity series: hippocampal interneuron classifications–making things as simple as possible, not simpler. Trends Neurosci 26:564–571
Maingret F, Lauri SE, Taira T, Isaac JT (2005) Profound regulation of neonatal CA1 rat hippocampal GABAergic transmission by functionally distinct kainate receptor populations. J Physiol 567:131–142
McEvoy JP, Allen TB (2002) The importance of nicotinic acetylcholine receptors in schizophrenia, bipolar disorder and Tourette's syndrome. Curr Drug Targets CNS Neurol Disord 1:433–442
Palva JM, Lamsa K, Lauri SE, Rauvala H, Kaila K, Taira T (2000) Fast network oscillations in the newborn rat hippocampus in vitro. J Neurosci 20:1170–1178
Pantazopoulos H, Stone D, Walsh J, Benes FM (2004) Differences in the cellular distribution of D1 receptor mRNA in the hippocampus of bipolars and schizophrenics. Synapse 54(3):147–155
Robinson RB, Siegelbaum SA (2003) Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 65:453–480
Rosene DL, Van Hoesen GW (1987) The hippocompal formation of the primate brain. In: Peters A, Jones EG (eds) Cerebral cortex, vol 6, Further aspects of cortical function including hippocampus. Plenum Press, New York, pp 345–456
Schaefer AT, Helmstaedter M, Schmitt AC, Bar-Yehuda D, Almog M, Ben-Porat H, Sakmann B, Korngreen A (2007) Dendritic voltage-gated K+ conductance gradient in pyramidal neurones of neocortical layer 5B from rats. J Physiol 579:737–752
Stone DJ, Walsh J, Benes FM (1999) Localization of cells preferentially expressing GAD(67) with negligible GAD(65) transcripts in the rat hippocampus. A double in situ hybridization study. Brain Res Mol Brain Res 71:201–209
Todtenkopf MS, Benes FM (2001) Distribution of glutamate decarboxylase 65 immunoreactive puncta on pyramidal and non-pyramidal neurons in hippocampus of schizophrenic brain. Synapse 29(4):323–332
Traub RD, Cunningham MO, Gloveli T, LeBeau FE, Bibbig A, Buhl EH, Whittington MA (2003) GABA-enhanced collective behavior in neuronal axons underlies persistent gamma-frequency oscillations. Proc Natl Acad Sci USA 100:11047–11052
Traub RD, Bibbig A, LeBeau FE, Buhl EH, Whittington MA (2004) Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro. Annu Rev Neurosci 27:247–278
Veldic M, Guidotti A, Maloku E, Davis JM, Costa E (2005) In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci USA 102:2152–2157
Vincent SL, Adamec E, Sorensen I, Benes FM (1994) The effects of chronic haloperidol administration on GABA- immunoreactive axon terminals in rat medial prefrontal cortex. Synapse 17:26–35
Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA (2000) Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57:237–245
Whittington MA, Doheny HC, Traub RD, LeBeau FE, Buhl EH (2001) Differential expression of synaptic and nonsynaptic mechanisms underlying stimulus-induced gamma oscillations in vitro. J Neurosci 21:1727–1738
Woo TU, Walsh JP, Benes FM (2004) Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Arch Gen Psychiatry 61:649–657
Woo TU, Shrestha K, Amstrong C, Minns MM, Walsh JP, Benes FM (2007) Differential alterations of kainate receptor subunits in inhibitory interneurons in the anterior cingulate cortex in schizophrenia and bipolar disorder. Schizophr Res 96:46–61
Yang EJ, Harris AZ, Pettit DL (2007) Synaptic kainate currents reset interneuron firing phase. J Physiol 578:259–273
Zhu X, Raina AK, Smith MA (1999) Cell cycle events in neurons. Proliferation or death? Am J Pathol 155:327–329
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg 2010
About this chapter
Cite this chapter
Benes, F.M. (2010). The Neurobiology of Bipolar Disorder: From Circuits to Cells to Molecular Regulation. In: Manji, H., Zarate Jr., C. (eds) Behavioral Neurobiology of Bipolar Disorder and its Treatment. Current Topics in Behavioral Neurosciences, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2010_75
Download citation
DOI: https://doi.org/10.1007/7854_2010_75
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-15756-1
Online ISBN: 978-3-642-15757-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)