Article thumbnail

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

By Guillermo Gonzalez-Burgos, Kenneth N. Fish and David A. Lewis


Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1998). A highly sensitive immunofluorescence procedure for analyzing the subcellular distribution of GABAA receptor subunits in the human brain,”
  2. (1998). A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey,”
  3. (2009). A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia,”
  4. (2008). A neural coding scheme formed by the combined function of gamma and theta oscillations,”
  5. (2011). A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia,”
  6. (2007). a s a r - E r o g l u ,A .B r a n d ,H .H i l d e b r a n d t ,K .K .K e d z i o r
  7. (2010). A small number of open Ca2+ channels trigger transmitter release at a central GABAergic synapse,”
  8. (1998). A.Fisahn,F.G.Pike,E.H.Buhl,andO.Paulsen,“Cholinergic induction of network oscillations at 40Hz in the hippocampus in vitro,”
  9. (2010). A.R.Woodruff,S.A.Anderson,andR.Yuste,“Theenigmatic function of chandelier cells,”
  10. (2010). Abnormal neural oscillations and synchrony in schizophrenia,”
  11. (2003). Abnormal neural synchronyinschizophrenia,”TheJournalofNeuroscience,vol.
  12. (1997). Action potential initiation and backpropagation
  13. (1997). Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on α-subunit isoform,”
  14. (2009). Activity-dependent development of inhibitory synapses and innervation pattern: role of GABA signalling and beyond,”
  15. (2010). Adolescence: what do transmission, transition, and translation have to do with it?”
  16. (2008). alez-Burgos, “Neuroplasticity of neocortical circuits in schizophrenia,”
  17. (2010). Alterations of cortical GABA neurons and network oscillations in schizophrenia,”
  18. (2011). Altered expression of regulators of the cortical chloride transporters
  19. (1995). Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons,”
  20. (2001). An integrative theory of prefrontal cortex function,”
  21. (1996). Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo,”
  22. (1998). Ankyrin(G) is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing,”
  23. (2010). as,“Differentialdistributionof KCC2 along the axo-somato-dendritic axis of hippocampal principal cells,”
  24. (2005). Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuronprincipal neuron synapse,”
  25. (2010). Asynchronous release of GABA via tonic cannabinoid receptor activation at identified interneuron synapses in rat CA1,”
  26. (2009). Asynchronous transmitter release from cholecystokinincontaining inhibitory interneurons is widespread and targetcellindependent,”TheJournalofNeuroscience,vol.29,no.36,
  27. (1999). Brain development during childhood and adolescence: a longitudinal MRI study,”
  28. (2005). Brain synaptogenesis and epigenesis,”
  29. (2003). Brain-stateand cell-type-specific firing of hippocampal interneurons in vivo,”
  30. (2002). C h o i ,B .M o r a l e s ,H .K .L e e ,a n dA .K i r k w o o d , “Absence of long-term depression in the visual cortex of glutamicaciddecarboxylase-65knock-outmice,”TheJournal of
  31. (2009). Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex,”
  32. (2007). Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo,”
  33. (2002). Cell typeand input-specific differences in the number and subtypes of synaptic GABA(A) receptors in the hippocampus,”
  34. (2005). Changes in synaptic structure underlie the developmental speeding of AMPA receptor-mediated EPSCs,”
  35. (1998). Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro,”
  36. (2008). Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia,”
  37. (1997). Cleft palate and decreased brain γ-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase,”
  38. (2005). Cluster analysis-basedphysiologicalclassificationandmorphological properties of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex,”
  39. (2011). Cognitive control deficits in schizophrenia: mechanisms and meaning,”
  40. (2008). Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms,”
  41. (2008). Complementary modulation of somatic inhibition by opioids and cannabinoids,”
  42. (2005). Complementary roles of cholecystokinin- and parvalbuminexpressing GABAergic neurons in hippocampal network oscillations,”
  43. (2008). Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia,”
  44. (2010). Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons,”
  45. (2005). Cortical inhibitory neurons and schizophrenia,”
  46. (2009). Cortical oscillatory activity is critical for working memory as revealed by deficits in early-onset schizophrenia,”
  47. (2003). Decline of the critical period of visual plasticity is concurrent with the reduction of NR2B subunit of the synaptic NMDA receptor in layer 4,”
  48. (2000). Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gammaaminobutyric acid neurons in subjects with schizophrenia,”
  49. (2009). Deficiency of the 65 kDa isoform of glutamic acid decarboxylase impairs extinction of cued but not contextual fear memory,”
  50. (2005). Deletion of the NR2A subunit prevents developmental changes of NMDA-mEPSCs in cultured mouse cerebellar granule neurones,”
  51. (2010). Dendritic mechanisms underlying rapid synaptic activation of fast-spiking hippocampal interneurons,”
  52. (2010). Development of calciumpermeable AMPA receptors and their correlation with NMDA receptors in fast-spiking interneurons of rat prefrontalcortex,”JournalofPhysiology,vol.588,pp.2823–2838,
  53. (2011). Development of inhibitory timescales in auditory cortex,”
  54. (1999). Development of the GABA system in organotypic culture of hippocampal and cerebellar slices from a 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient mice,”
  55. (2010). Developmental changes in GABAergic mechanisms in human visual cortex across the lifespan,” Frontiers in Cellular Neuroscience,
  56. (2005). Developmental changesinparvalbuminregulatepresynapticCa2+ signaling,”
  57. (2010). Developmental co-regulation of the beta and gamma GABAA receptor subunits with distinct alpha subunits in the human dorsolateral prefrontal cortex,”
  58. (1995). Developmental expression of parvalbumin mRNA in the cerebral cortex and hippocampus of the rat,”
  59. (2010). Developmental trajectories of transcripts regulating GABA neurotransmission in monkey prefrontal cortex,”
  60. (1996). Differences between somatic and dendritic inhibition in the hippocampus,”
  61. (2007). Different transmitter transients underlie presynaptic cell type specificity of GABAA, slow and GABAA,
  62. Differential distribution of proteins regulating GABA synthesis and reuptake in axon boutons of subpopulations of cortical interneurons,” Cerebral Cortex.
  63. (2005). Differential involvement of oriens/pyramidale interneurones in hippocampal network oscillations in vitro,” J o u r n a lo fP h y s i o l o g y ,
  64. (1999). Differential regulation of synaptic GABA(A) receptors by cAMP-dependent protein kinase in mouse cerebellar and olfactory bulb neurones,”
  65. (2000). Differential sensitivity to Zolpidem of IPSPs activated by morphologically identified CA1 interneurons in slices of rat hippocampus,”
  66. (1996). Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells,”
  67. (1998). Differentially interconnected networks of GABAergic interneurons in the visual cortex of the cat,”
  68. (2000). Distinct frequency preferences of different types of rat hippocampal neurones in response to oscillatory input currents,”
  69. (2004). Distinct roles for the kainate receptor subunits
  70. (2010). Distinct synaptic properties of perisomatic inhibitory cell types and their different modulation by cholinergic receptor activation in the CA3 region of the mouse hippocampus,” The European The
  71. (1994). Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites,”
  72. (1999). Dual intracellular recordings and computational models of slow inhibitory postsynaptic potentials in rat neocortical and hippocampal slices,”
  73. (1995). E.H.Buhl,S.R.Cobb,K.Halasy,andP.Somogyi,“Properties of unitary IPSPs evoked by anatomically identified basket cells in the rat hippocampus,”
  74. (2010). Effe c to fa c u t ep s y c h o l o g i c a ls t r e s so np r e f r o n t a l GABA concentration determined by proton magnetic resonance spectroscopy,”
  75. (2002). Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex,”
  76. (2010). Elevated gamma-aminobutyric acid levels in chronic schizophrenia,”
  77. (2010). Emergence of cortical inhibition by coordinated sensory-driven plasticity at distinct synaptic loci,”
  78. (2008). ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms,”
  79. (2008). Erd´ e l y i ,G .S z a b´ o, and
  80. (1994). Ermentrout, “When inhibition not excitation synchronizes neural firing,”
  81. (2010). Evidence for excessive frontal evoked gamma oscillatory activity in schizophrenia during working memory,”
  82. (2002). Excitatory actions of GABA during development: the nature of the nurture,”
  83. Exploring intermediate phenotypes with EEG: working memory dysfunction in schizophrenia,”
  84. (2003). Expression of GABA transporters,
  85. (2010). Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing human and in schizophrenia,”
  86. (2008). F i s h ,R .A .S w e e t ,A .J .D e o ,a n dD .A .L e w i s , “An automated segmentation methodology for quantifying immunoreactive puncta number and fluorescence intensity in tissue sections,”
  87. (1997). Fast IPSPs elicited via multiple synaptic release sites by different types of GABAergic neurone in the cat visual cortex,”
  88. (2002). Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks,”
  89. (1995). Foundations of Cellular Neurophysiology,
  90. (2010). From maps to mechanisms through neuroimaging of schizophrenia,”
  91. (2008). Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate prefrontal cortex,”
  92. (2005). Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex,”
  93. (2009). GABA A receptors: subtypes providediversityoffunctionandpharmacology,”Neuropharmacology,
  94. (2008). GABA and synaptic inhibition of mouse cerebellum lacking glutamate decarboxylase 67,”
  95. (2010). GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study,”
  96. (2010). GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression,”
  97. (2008). GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia,”
  98. (2010). GABA release at terminals of CCKinterneurons: synchrony, asynchrony and modulation by cannabinoid receptors
  99. (2009). GABA transporter GAT1 prevents spillover at proximal and distal GABA synapses onto primate prefrontal cortex neurons,” J o u r n a lo fN e u r o p h y s i o l o g y ,
  100. (1996). GABA transporter heterogeneity: pharmacology and cellular localization,”
  101. (2003). GABA transporter-1 (GAT1)-deficient mice: differential tonic activation of GABA versus GABA receptors in the hippocampus,”
  102. (2001). GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons,”
  103. (2004). GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications,”
  104. (2008). GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1,”
  105. (2007). GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex,”
  106. (1995). Gamma (40–100Hz) oscillation in the hippocampus of the behaving rat,”
  107. (1996). Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model,”
  108. (2008). Gamma oscillatory firing reveals distinct populations of pyramidal cells in the CA1 region of the hippocampus,”
  109. (1998). Gammafrequencyoscillationinthehippocampusoftherat: intracellular analysis in vivo,”
  110. (1995). GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex,”
  111. (2004). Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons,”
  112. (2011). Glutamate receptor subtypes mediating synaptic activation of prefrontal cortex neurons: relevance for schizophrenia,”
  113. (2003). H o w a r d ,D .S .R i z z u t o ,J .B .C a p l a ne ta l . ,“ G a m m a oscillationscorrelatewithworkingmemoryloadinhumans,”
  114. Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons,”
  115. (2008). Hosl et al., “Reversal of pathological pain through specific spinal GABAA receptor subtypes,”
  116. (2007). How can drug discovery for psychiatric disorders be improved?”
  117. (2010). Identification of the currentgeneratorunderlyingcholinergicallyinducedgamma frequency field potential oscillations in the hippocampal CA3 region,” J o u r n a lo fP h y s i o l o g y ,
  118. (2003). Identified sources and targets of slow inhibition in the neocortex,”
  119. (2002). Impaired prefrontal inhibition in schizophrenia: relevance for cognitive dysfunction,”
  120. (2006). Impairments in frontal cortical γ synchrony and cognitive control in schizophrenia,”
  121. (2000). Inhibition-based rhythms: experimental andmathematicalobservationsonnetworkdynamics,”International
  122. (2005). Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks,”
  123. (2009). Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition,”
  124. (2009). Interneuron diversity in layers 2-3 of monkey prefrontal cortex,”
  125. (2009). Interneurons hyperpolarize pyramidal cells along their entiresomatodendriticaxis,”Nature
  126. (2003). Jeffe r y s ,M .R .C e l i o ,a n dB .S c h w a l l e r , “Parvalbumin-deficiency facilitates repetitive IPSCs and gamma oscillations in the hippocampus,”
  127. (1999). K a s h ,L .H .T e c o t t ,C .H o d g e ,a n dS .B a e k k e s k o v , “Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase,”
  128. (1997). K a s h ,R .S .J o h n s o n ,L .H .T e c o t te ta l . ,“ E p i l e p s yi nm i c e deficient in the 65-kDa isoform of glutamic acid decarboxylase,”
  129. (2007). Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase,”
  130. (2008). Koml´ osi et al., “Complex events initiated by individual spikes in the human cerebral cortex,”
  131. (2009). Koml´ osi et al., “Regulation of cortical microcircuits by unitary GABA-mediated volume transmission,”
  132. (2011). Lamina-specific alterations in cortical GABAA receptor subunit expression in schizophrenia,”
  133. (2009). Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia,”
  134. (2008). Lessons to take home from
  135. (1993). Local circuit neurons of developing and mature macaque prefrontal cortex: Golgi and immunocytochemical characteristics,”
  136. (2005). Localization of calcium-binding proteins in physiologically and morphologically characterized interneurons of monkey dorsolateral prefrontal cortex,”
  137. (2010). M i n z e n b e r g
  138. (2009). M.M.BehrensandT.J.Sejnowski,“Doesschizophreniaarise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?”
  139. (2002). Mapping of the benzodiazepine recognition site on GABA(A) receptors,”
  140. (2010). Maturation of GABAergic inhibition promotes strengthening of temporally coherent inputs among convergent pathways,”
  141. (2010). Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia,” Psychological Medicine,
  142. (2003). Mechanisms of gamma oscillations in the hippocampus of the behaving rat,”
  143. (1996). Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures,”
  144. (1999). Modulation of bistratified cell IPSPs and basket cell IPSPs by pentobarbitone sodium, diazepam and Zn2+: dual recordings in slices of adult rat hippocampus,”
  145. (2006). Moln´ a r ,S .O l
  146. (2010). More is less: a disinhibited prefrontal cortex impairs cognitive flexibility,”
  147. (2011). Multiple origins of the cortical gamma rhythm,”
  148. (2008). Nanodomain coupling between Ca2+ channels and Ca2+ sensors promotes fast and efficient transmitter release at a cortical GABAergic synapse,” Neuron,v o l .5 7 ,n o .4 ,p p .
  149. (2009). Network mechanisms of gamma oscillations in the CA3 region of the hippocampus,”
  150. (2010). Neural synchrony and the development of cortical networks,”
  151. (2008). Neuregulin 1 in neural development, synaptic plasticity and schizophrenia,”
  152. (2011). Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons,”
  153. (2010). Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbuminpositive interneurons,”
  154. (2009). Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia,”
  155. (1998). Neuronal and glial localization of GAT-1, a highaffinity γ- aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex,”
  156. (2008). Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations,”
  157. (2009). Neuronal gamma-band synchronization as a fundamental process in cortical computation,”
  158. (2004). Neuronal olscillations in corticalnetworks,”Science,vol.304,no.5679,pp.1926–1929,
  159. (2010). Neurophysiological and computational principles of cortical rhythms in cognition,”
  160. (2010). NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial representations, and working memory,”
  161. (2007). NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons,”
  162. (2010). No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia,”
  163. (2005). No postnatal doubling of number of neurons in human Broca’s areas (Brodmann areas 44 and 45)? A stereological study,”
  164. (1997). NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex,”
  165. (2010). o p e l l ,M .A .K r a m e r ,P .M a l e r b a ,a n dM .A .W h i t t i n g t o n , “Are different rhythms good for different functions?” Frontiers in Human Neuroscience,
  166. (2008). Omrani et al., “GAT-1 regulates both tonic and phasic GABA(A) receptor-mediated inhibition in the cerebral cortex,”
  167. (2009). Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex,”
  168. (2010). Overview of normal and abnormal cortical oscillations schizophrenia,”
  169. (2009). Parvalbumin neurons and gamma rhythms enhance cortical circuit performance,”
  170. (2010). Parvalbumincontaining fast-spiking basket cells generate the field potential oscillations induced by cholinergic receptor activation in the hippocampus,”
  171. (2007). ParvalbuminisamobilepresynapticCa2+ bufferinthecalyx of held that accelerates the decay of Ca2+ and short-term facilitation,”
  172. (2005). Perisomatic feedback inhibition underlies cholinergically induced fast network oscillations in the rat hippocampus in vitro,”
  173. (2008). Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex,”
  174. (2003). Postnatal development of pre- and postsynaptic GABA markers at chandelier cell connections with pyramidal neurons in monkey prefrontal cortex,”
  175. (2009). Postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex,”
  176. (2008). Postnatal differentiation of basket cells from slow to fast signaling devices,”
  177. (2010). Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes,”
  178. (1999). Postsynaptic glutamate receptors and integrative properties of fastspiking interneurons in the rat neocortex,”
  179. (2007). Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters,”
  180. (2010). Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia,”
  181. (2010). Presynaptic kainate receptor activation preserves asynchronousGABAreleasedespitethereductioninsynchronous release from hippocampal cholecystokinin interneurons,”
  182. (2011). Probing GABA receptor function in schizophrenia with iomazenil,”
  183. Properties of excitatory synaptic responses in fast-spiking interneurons and pyramidal cells from monkey and rat prefrontal cortex,”
  184. (2009). Protracted developmental trajectories of GABAA receptor alpha1 and alpha2 subunit expression in primate prefrontal cortex,”
  185. (2011). Rapid developmental maturation of neocortical FS cell intrinsic excitability,”
  186. (2005). Rapid substrate-induced charge movements of the
  187. (1992). receptor responses during development of the visual cortex,”
  188. (2007). Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior,”
  189. (2011). Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia,”
  190. (2009). Reduction of brain gamma-aminobutyric acid (GABA) concentrations in early-stage schizophrenia patients:
  191. (2008). Region-specific changes in gamma and beta2 rhythms in NMDA receptor dysfunction models of schizophrenia,”
  192. (1999). Regional distributionandrelativeamountsofglutamatedecarboxylase isoforms in rat and mouse brain,”
  193. (2010). Regulation of fast-spiking basket cell synapses by the chloride channel
  194. (2010). Relationship of cannabinoid CB1 receptor and cholecystokinin immunoreactivity in monkey dorsolateral prefrontal cortex,”
  195. (2008). Reliability, synchrony and noise,”
  196. (2009). Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans,”
  197. (2010). Rethinking schizophrenia,”
  198. (2003). S.Mahendrasingam,C.A.Wallam,andC.M.Hackney,“Two approaches to double post-embedding immunogold labeling of freeze-substituted tissue embedded in low temperature
  199. (1995). S.R.Cobb ,E.H.Buhl,K.H alasy ,O .P aulsen,andP .Somogyl, “Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons,”
  200. (2005). S.Stroup ,J .P .M cE voyetal.,“Effectiveness of antipsychotic drugs in patients with chronic schizophrenia,”
  201. (2002). Schizophrenia as a disorder of neurodevelopment,”
  202. (2010). Schizophrenia: the drug deadlock,”
  203. (2005). Sdrulla et al., “NKCC1 transporter facilitates seizures in the developing brain,”
  204. (2000). Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy,”
  205. (2009). Selective expression of ErbB4 in interneurons, but not pyramidal cells, of the rodent hippocampus,”
  206. (1997). Shaping of IPSCs by endogenouscalcineurinactivity,”TheJournalofNeuroscience,
  207. (2006). Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuronnetworksbyhomogenizingfiringrates,”Neuron,
  208. (1998). Silent synapses in the developing rat visual cortex: evidence for postsynaptic expressionofsynapticplasticity,”
  209. (1996). Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex,”
  210. (2010). slow): causes and consequences,”
  211. (2008). Spectrin and ankyrin-based cytoskeletons at polarized domains in myelinated axons,”
  212. (2004). Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro,”
  213. (2008). Structural mechanisms underlying benzodiazepine modulation of the GABA(A) receptor,”
  214. (1997). Submillisecond AMPA receptor-mediated signaling at a principal neuron- interneuron synapse,”
  215. (2005). Subtype-specific GABA transporter antagonists synergistically modulate phasic and tonic GABAA conductances in rat neocortex,”
  216. (2008). Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia,”
  217. (2004). Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development,”
  218. (2003). Synapse density regulates independence at unitary inhibitory synapses,”
  219. (2009). Synaptic cross talk between perisomatic-targeting interneuron classes expressing cholecystokinin and parvalbumin in hippocampus,”
  220. (2006). Synaptic currents in anatomically identified CA3 neurons during hippocampal gamma oscillations in vitro,”
  221. (2007). Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks,”
  222. (2004). Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6,” Pflugers Archiv E u r o p e a nJ o u r n a lo fP h y s i o l o g y ,
  223. (1994). Synaptogenesis in the prefrontal cortex of rhesus monkeys,”
  224. (1995). Synchronized oscillation in interneuron networks driven by metabotropic glutamate receptor activation,”
  225. (1995). Synchronous development of pyramidal neuron dendritic spines and parvalbumin-immunoreactive chandelier neuron axon terminals in layer III of monkey prefrontal cortex,”
  226. (2007). Szabadics et al., “Output of neurogliaform cells to various neuron types in the human and rat cerebral corte,”
  227. (2000). The adolescent brain and age-related behavioral manifestations,”
  228. (2007). The cellular, molecular and ionic basisofGABAreceptorsignalling,”ProgressinBrainResearch,
  229. (2011). The chandelier neuron in schizophrenia,”
  230. (2009). The development of neural synchrony reflects late maturation and restructuring of functional networks
  231. (1994). The development of parvalbumin-immunoreactivity in the neocortex of the mouse,”
  232. (2004). The GABA-glutamate connection in schizophrenia: which is the proximate cause?”
  233. (2011). The GABAA receptor {alpha}+ {beta}- interface: a novel target for subtype selective drugs,”
  234. (2010). The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits,”
  235. (2010). The rise of a new
  236. The role of phase synchronization in memory processes,”
  237. (1999). The role of the synthetic enzyme GAD65 in the control of neuronal γ-aminobutyric acid release,”
  238. (1999). Thomson, “IPSPs elicited in CA1 pyramidal cells by putative basket cells in slices of adult rat hippocampus,”
  239. (2006). TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluor ophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates,”
  240. (2009). Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons,”
  241. (2001). Translating developmental time across mammalian species,”
  242. (1998). Two isoforms of glutamate decarboxylase:
  243. (1999). Two networks of electrically coupled inhibitory neurons in neocortex,”
  244. Voltage- and site-dependent controlofthesomaticimpactofdendriticIPSPs,”TheJournal of
  245. (2001). Voltage-gated sodium channels shape subthreshold EPSPs in layer 5 pyramidal neurons from rat prefrontal cortex,”
  246. (1996). What are the functional consequences of neurocognitive deficits in schizophrenia?”
  247. (2009). X u ,S .A .A n d e r s o n ,a n dR .Y u s t e ,“ D e p o -larizing effect of neocortical chandelier neurons,”
  248. (2007). βIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG,”
  249. (2004). βIV spectrins are essential for membrane stabilityandthemolecularorganizationofnodesofRanvier,”