Abstract
Inhibitory local circuit neurons (LCNs), often called interneurons, have vital roles in the development and function of cortical networks. Their inhibitory influences regulate both the excitability of cortical projection neurons on the level of individual cells, and the synchronous activity of projection neuron ensembles that appear to be a neural basis for major aspects of cognitive processing. Dysfunction of LCNs has been associated with neurological and psychiatric diseases, such as epilepsy, schizophrenia, and autism. Here we review progress in understanding LCN fate determination, their nonradial migration to the cortex, their maturation within the cortex, and the contribution of LCN dysfunction to neuropsychiatric disorders.
Similar content being viewed by others
INTRODUCTION
The cerebral cortex mediates higher-order cognitive processing, learning, and memory. These functions are made possible by intricate interactions of glia, excitatory projection neurons, and inhibitory interneurons. Most cortical interneurons, also termed local circuit neurons (LCNs), primarily use the neurotransmitter GABA (γ-aminobutyric acid) to modulate neural activity. LCNs comprise about 20% of the cortical neurons and can be subclassed based on neurochemical markers, connectivity, and physiological properties (Ascoli et al, 2008; DeFelipe et al, 2013; Kepecs and Fishell, 2014). Nearly all LCNs can be separated into three neurochemically distinct subgroups that express the calcium binding protein parvalbumin (PV), neuropeptide somatostatin (SST), or the ionotropic serotonin receptor 5HT3aR (Lee et al, 2010). The groups are biased for additional distinctions. For example, the PV subgroup tends to have a very rapid and nonaccommodating ‘fast-spiking’ firing response to injected current and to target pyramidal neuron somata, proximal dendrites, or axon-initial segments. The SST subgroup tends to have burst spiking or accommodating features and to target distal dendrites. The 5HT3aR subgroup includes vertically oriented, bipolar or bitufted LCNs that tend to target other interneurons. As we shall see below, the PV-SST-5HT3aR subgroupings also have biases for different spatial and temporal origins in the ventral forebrain.
LCNs have a vital role in the development and function of cortical networks. Dysfunction of LCNs has been associated with neurological and psychiatric diseases, such as epilepsy, schizophrenia, and autism. Here we review the progress in understanding LCN fate determination, their nonradial migration to the cortex, their maturation within the cortex, and the contribution of LCN dysfunction to neuropsychiatric disorders.
SPATIAL AND TEMPORAL ORIGINS OF CORTICAL INTERNEURONS IN THE TELENCEPHALON
In general, the CNS develops from the neural tube by the radial migration of neurons from the proliferative zones along the tube’s medial wall, to the mantle zones at the tube’s periphery. Cortical projection neurons (glutamatergic, excitatory) follow this scenario. In contrast, cortical LCNs originate in subcortical areas of the telencephalon, in the same general region where the GABAergic projection neurons of the basal ganglia are being produced. The reason for this arrangement is not known, but in order to have a mixture of excitatory and inhibitory neurons in the evolving cerebral cortex the dorsal proliferative zone, generating glutamatergic neurons, could have been modified with the capacity to generate GABAergic ones. However, this would have been a highly complex adjustment as distinct extracellular signaling systems and transcription factor cascades are involved in glutamatergic vs GABAergic fate determination (Hebert and Fishell, 2008). Alternatively, GABAergic neurons could be imported into the evolving cortex from more ventrally located parts of the neural tube that were already producing these cells. Evolution chose importation, and although there has been some support for the notion that cortical LCN origins in primates may include the cortex itself (Jakovcevski et al, 2011; Letinic et al, 2002; Yu and Zecevic, 2011), the bulk of cortical LCN neurogenesis in humans and other primates occurs in the ventral, subcortical forebrain (Hansen et al, 2013; Ma et al, 2013). The following section discusses the main spatial and temporal origins of cortical LCNs, based mainly on studies in rodents, and their relationship with LCN subgroup fate.
The rostral forebrain, or telencephalon, consists of cortical and subcortical developmental domains. The subcortical (also termed subpallial or pallidal) telencephalon consists of five major subdivisions: the lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE), septum (SE), and preoptic area (POA). Multiple studies in rodents, generally supported by additional studies in ferrets and primates (Anderson et al, 2002; Hansen et al, 2013; Ma et al, 2013), show that the MGE and CGE are the primary sources of cortical LCNs, with a small, diverse subset also originating in the POA (Gelman et al, 2009).
Medial Ganglionic Eminence
The ganglionic eminences can be divided into medial (MGE), lateral (LGE), and caudal (CGE) ganglionic eminence based on their dorsal–ventral and rostral–caudal locations within the subpallium. The MGE gives rise to about 60% of LCNs in rodents. Studies using transgenic mice found that both the somatostatin (SST)- and parvalbumin (PV)-expressing subgroups originate mainly in the MGE (Butt et al, 2005; Wonders and Anderson, 2006; Xu et al, 2004). On the basis of the study of human holoprosencephaly, in which the MGE-like region of the human ventral forebrain fails to form, this tissue also appears to generate PV- and SST-expressing LCNs in humans (Fertuzinhos et al, 2009).
Dissections and transplantations of subregions of rodent MGE found a strong bias for SST-expressing LCNs to be generated in the dorsal MGE, whereas PV-LCNs are generated by both dorsal and ventral MGE regions (Flames et al, 2007; Inan et al, 2012; Wonders et al, 2008). Thus far, only one LCN type has been identified as having a distinct MGE source. The axo-axonic (chandelier) cell, a fast-spiking subclass of LCN that also frequently expresses detectable levels of PV, has a strong bias for origination within the ventral-most region of the MGE at the end of cortical neurogenesis (Inan et al, 2012; Taniguchi et al, 2013).
In terms of birthdate, MGE LCNs follow the same general inside-out relationship of birthdating to laminar location in the cortex as do the projection neurons (Butt et al, 2005; Xu et al, 2004). Within a given layer, PV and SST LCNs have similar birthdates. However, as the ratio of PV to SST LCNs is roughly 1.5 : 1 in layers 5 and 6, but is closer to 3 : 1 in layers 2 and 3 (Xu et al, 2010b), a higher proportion of all SST LCNs are born earlier in the neurogenic period than is the proportion of all PV-LCNs.
In addition to location and time, retroviral lineage analysis suggests that PV and SST interneurons can be derived from the same radial glial cell (Brown et al, 2011). To connect this finding with spatial and temporal biases for differential origins of SST- and PV-expressing LCNs, evidence suggests that PV interneurons preferentially originate from intermediate progenitor divisions within the subventricular zone. This suggestion is based on the analysis of mice lacking cyclin D2, which is expressed in intermediate progenitors throughout the telencephalon and promotes their proliferation, and which have a reduction of PV but not SST interneurons in the neocortex and hippocampus (Glickstein et al, 2007a, 2007b). Interestingly, there appear to be less cyclin D2-expressing cells in the dorsal-most MGE (Glickstein et al, 2007a).
Caudal Ganglionic Eminence
The CGE is the other main subpallial source of cortical LCNs (Anderson et al, 2001; Nery et al, 2002, 2003), generating at least 30% (Miyoshi et al 2010). Morphologically, the CGE exists as a caudal fusion of the MGE and LGE that begins at the coronal level of the mid-thalamus. Transplantation studies as well as genetic fate mapping have demonstrated that the CGE generates a remarkable diversity of LCN subclasses, variably overlapping, based on their expression of calretinin, vasoactive intestinal protein (VIP), reelin, and NPY (Butt et al, 2005; Miyoshi et al, 2007, 2010). Remarkably, nearly all of these subgroups express the 5HT3aR (Tricoire et al, 2010). An additional feature of the CGE is that LCNs from this region are born relatively late in neurogenesis, and do not follow the ‘inside-out’ relationship of birthdate to laminar location found for the MGE-derived cortical LCNs (Butt et al, 2005; Rymar and Sadikot, 2007; Xu et al, 2004).
Preoptic Area
The preoptic area (POA) is a telencephalic region ventral to the MGE that also expresses Nkx2.1 in progenitor cells (Flames et al, 2007). Using in utero electroporation as well as genetic fate mapping from Nkx5.1-expressing cells, the POA was recently shown to give rise to a small number of LCNs (Gelman et al, 2009). These were found mainly in the superficial cortex, and about a third expresses NPY but not SST, and tended to have a distinctive, rapidly adapting electrophysiological property. Interestingly, these preoptic-derived LCNs, unlike those developing from Nkx2.1+ progenitors in the MGE, do not express the transcription factor Lhx6 that, in the MGE, lies downstream of Nkx2.1 in the specification of PV- and SST-expressing LCNs.
CORTICAL INTERNEURON FATE DETERMINATION
As genetic fate-mapping and transplantation studies find clear biases for the generation of distinct cortical LCN subclasses from distinct subcortical progenitor domains, LCNs appear to be fate committed either at or shortly after cell cycle exit. Fate determination of the MGE-derived LCNs requires the transcription factor Nkx2.1 (Sussel et al, 1999; Xu et al, 2004, 2005). Upstream of Nkx2.1, the morphogen sonic hedgehog (SHH) is required for initial patterning of the Nkx2.1 domain in the MGE (Fuccillo et al, 2004), and to maintain Nkx2.1 expression in progenitors during neuronogenesis (Xu et al, 2005, 2010b). Downstream of Nkx2.1, Lhx6, a direct target of Nkx2.1 (Du et al, 2008), is expressed permanently in most MGE-derived LCNs from around the time of cell cycle exit (Lavdas et al, 1999; Liodis et al, 2007). Little is known about the transcriptional cascades leading to terminal maturation of cortical LCNs in the postnatal cortex, although Sox6 appears to be an important effector of Lhx6 signaling (Azim et al, 2009; Batista-Brito et al, 2009), and Satb1 also has a role downstream of Lhx6 (Close et al, 2012).
The molecular mechanisms underlying the differential fate determination of SST- vs PV-expressing LCNs in the MGE are not clear. It has been proposed that there are distinct progenitor domains within the MGE that give rise to different classes of LCNs (Flames et al, 2007). However, transplantation studies in which cells are labeled with markers that indicate they were still in the cell cycle shortly prior to transplantation, thus controlling for postmitotic migration within the proliferative zone, do not support the existence of such clear demarcations of domains committed to the generation of distinct LNC subclasses (Inan et al, 2012). Although the dorsal MGE is strongly biased for generating SST-expressing interneurons, PV-expressing LCNs are generated throughout the MGE.
To date, there has been relatively little progress in determining how distinct subclasses of LCNs become specified. In the MGE, SST-expressing LCNs appear to be specified at higher levels of Shh signaling, which appear to be present in the dorsal-most MGE, whereas PV-expressing LCNs require lower levels (Xu et al, 2010a). The putative transcription factor LMO4 may also promote PV-LCN fate (Au et al, 2013), but a connection between Shh signaling and LMO4 expression, not to mention factors responsible for interneuron subtype fate determination, has yet to be established.
Relative to MGE-derived LCNs, even less is known about the fate determination of the highly diverse subclasses of CGE-derived LCNs. On the top of the transcriptional hierarchy are two homeobox genes, Gsx1 and Gsx2. The transcription factors generally function in the specification of neuronal subclasses from LGE and CGE (Waclaw et al, 2009). Consistent with this role, elimination of Gsx2 results in a selective reduction of the CGE-derived vertically oriented CR+ population (Xu et al, 2010a). CoupTF2 is an additional transcription factor that controls the generation of CGE-derived interneurons (Lodato et al, 2011b), although many more, particularly those involved in interneuron subtype fate determination, remain to be discovered.
REGULATION OF CORTICAL INTERNEURON MIGRATION
Motogens
In their sojourn from the subcortical telencephalon into the cerebral cortex, LCNs face a variety of environments, for which a variety of chemorepulsion, chemoattraction, migratory substrates, and motogens contribute to the guidance process (Guo and Anton, 2014). First, multiple transplantation and culture studies have demonstrated that the LCN precursors (postmitotic, fate committed) have a strong migratory drive. Hepatocyte growth factor/scatter factor (HGF/SF), GDNF, BDNF, and NT4 are expressed by cells within the paths of migrating LCNs and have all been shown to stimulate tangential (nonradial glial-guided) migration (Polleux et al, 2002; Powell et al, 2001; Pozas and Ibáñez, 2005). Dopamine D1 receptor signaling also appears to promote LCN migration (Crandall et al, 2007). With a strong drive to migrate, the LCN precursors then use a combination of attractive and repulsive cues, together with permissive substrates, to guide their way into and across the overlying cortex.
Guidance Cues
To push the LCN precursors away from the proliferative zones lining the lateral ventricle, both Eph-ephrin and Slit-Robo signaling appears to function (Rudolph et al, 2010; Zhu et al, 1999; Zimmer et al, 2008). As the LCNs approach the developing striatal mantle zone, semaphorin-neuropilin- mediated chemorepulsion comes into play. Cortical LCNs express the Sema receptor, Neuropilin-2, and therefore migrate away from the semaphorin-expressing striatum, whereas striatal LCNs, which also derive mainly from Nkx2.1-expressing progenitors in the MGE, are neuropilin-2-negative (Le et al, 2007; MarÃn et al, 2001; Nobrega-Pereira et al, 2008). Interestingly, in contrast to cortical MGE-derived LCNs, Nkx2.1 expression is maintained in striatal LCNs (Marin et al, 2000; Nobrega-Pereira et al, 2008) and this expression prevents the expression of NPN2 and hence prevents the chemorepulsion away from striatum.
At least two chemoattractants affect the migration of LCN precursors into and within the cortical plate. First, a membrane-bound form of neuregulin1 appears to form a preferential track for ErbB4-expressing LCNs as they migrate from the striatum to the cortex (Flames et al, 2004). Neuregulin-ErbB4 signaling also functions to attract migrating LCNs into the cortex. In the cortex, SDF (Cxcl12) signaling via the Cxrc4 receptor on migratory LCNs results in a preference for their migration to track above and below the developing cortical plate (Stumm et al, 2003; Tiveron et al, 2006). Netrin signaling also contributes as attraction to cortical migratory streams, particularly the one that courses in layer 1, just below the pial surface (Sanchez-Alcaniz et al, 2011). The migratory drive to move in a generally lateral to medial direction across the cortex is not clear, but may involve LCN chemorepulsion of each other. This effect may be mediated by GABA (Cuzon et al, 2006), such that LCNs would tend to migrate down their own density gradient.
Cortical Plate Invasion and Migration Stoppage
Downregulation of SDF-CxCr4 signaling permits LCN invasion of the cortical plate from their migratory streams, both below the pial surface and in the cortical intermediate zone (Sanchez-Alcaniz et al, 2011; Wang et al, 2011). How the LCNs determine their final position is not known, but it is clear that at least the MGE-derived LCNs are following cues generated by the cortical pyramidal neurons (Hevner et al, 2004; Lodato et al, 2011a; Pla et al, 2006). Finally, GABA signaling may form an important stop signal for the LCNs, as upregulation of the Kcc2, which results in a shift of GABA-A receptor effects from depolarizing to hyperpolarizing, is associated with the termination of MGE-derived LCN migration (Bortone and Polleux, 2009). Genetically introduced hyperpolarization also can result in stoppage of CGE-derived LCN migration (De Marco Garcia et al, 2011). However, the extent to which this effect is due to altered intrinsic signaling, for example by changing mitochondrial dynamics, vs altered ability to respond to extrinsic depolarizing signals, remains to be determined.
Postmigratory Maturation
The final stage of LCN maturation involves terminal, postmigratory differentiation within the cortical plate, and can be divided into two stages. In the first stage, LCN attains their mature fates, defined by their distinctive connectivities, neurochemistries, and firing properties, which culminate in their attaining distinct functions within juvenile cortical circuits (Ascoli et al, 2008). A detailed discussion of this process is beyond the scope of this review, but interacting influences of transcription factors (Close et al, 2012; Cobos et al, 2005), neurotransmitters (Eggan et al, 2012), neurotrophins (Huang et al, 1999), cell adhesion molecules (Pillai-Nair et al, 2005), and their activities are clearly in play (Bartolini et al, 2013; Batista-Brito and Fishell, 2009). The second stage of LCN maturation occurs in concert with cortical circuitry maturation, a process that begins in the early postnatal time period but is not finally achieved in all cortical regions until adolescence or young adulthood. For example, PV expression by chandelier LCN axon terminals reaches a peak in monkey prefrontal cortex just prior to the initiation of excitatory axon pruning, raising the possibility that interneuron maturation may be directing the refinement of cortical circuitry (Anderson et al, 1995). Indeed, studies in GABA-deficient transgenic mice clearly demonstrate a role of LCN function in the alterations of excitatory connectivity that accompany critical period plasticity (Hensch, 2005). As we shall discuss below, recent evidence links a specific system, neurogulin-Erbb4 signaling, in regulating both PV-LCN synaptogenesis and cortical excitatory neuron pruning in a manner that may shed light on an etiology of schizophrenia (Del Pino et al, 2013).
NEURODEVELOPMENTAL DISORDERS ARISING FROM DYSFUNCTIONAL CORTICAL INTERNEURONS
As reviews of the associations between disruption of LCN function and neuropsychiatric disorders have been published recently (Inan et al, 2013; Lewis et al, 2012; Marin, 2012), this section will focus on a few LCN–mental illness links to schizophrenia that are bolstered by data from mouse models and that also relate to developmental points discussed above (Figure 1).
22q11.2 Deletion Syndrome (22qDS)
One of the best-established genetic factors underlying the risk of developing schizophrenia is the microdeletion in chromosomal region 22q11.2 (Bassett et al, 2010). 22qDS (DiGeorge syndrome, velocardiofacial syndrome) occurs in roughly 1 in 3000 births (Shprintzen et al, 2005). Patients display impairments in a variety of cognitive tasks (Karayiorgou et al, 2010) and roughly 30% will receive the diagnosis of schizophrenia (Murphy et al, 1999; Pulver et al, 1994). In fact, this mutation constitutes ∼1–2% of the sporadic cases of schizophrenia (Bassett et al, 2008; Xu et al, 2008).
Using a mouse model of 22q11.2 deletion syndrome, Meechan et al. showed that the distribution of PV+ cortical LCNs is altered in the 22qD mouse cortex, although the total number of PV+ neurons is not changed (Meechan et al, 2009). The presence of this pathology in mouse prefrontal cortex, along with multiple behaviorial deficits associated, like schizophrenia, with PFC dysfunction, also supports the validity of this model (Meechan et al, 2013). Both Shh and Cxcr4 signaling are also altered in these mice, raising the possibility that altered LCN subtype fate determination along with migrational abnormalities may contribute to the schizophrenia-related phenotypes in both mice and people with 22qDS (Marin, 2012; Maynard et al, 2013; Meechan et al, 2012b).
Neuregulin-ErbB4 Signaling in Schizophrenia
Numerous studies identified ErbB4 as a candidate susceptibility gene for schizophrenia (for reviews, see Buonanno, 2011; Rico and Marin, 2011). ErbB4 protein is a receptor tyrosine kinase preferentially expressed by PV- and SST-expressing cortical LCNs (Neddens et al, 2011). The Nrg1-ErbB4 interaction has a prominent role in many aspects of neuronal development, including neuronal migration, axon guidance and synapse formation, and plasticity (Mei and Xiong, 2008; Rico and MarÃn, 2011). ErbB4 mutant mice display hyperactivity, impaired working memory, and decreased PPI (Barros et al, 2009; Golub et al, 2004; Stefansson et al, 2002). Early disruption of ErbB4 using GFAP-Cre (all neural cells) or Dlx5/6-Cre (all forebrain GABAergic cells) mice decreased excitatory synapses, spine density, chandelier axon synapses, synaptic transmission between cortical LCNs and projection neurons, and also impaired prepulse inhibition (PPI) (Barros et al, 2009; Fazzari et al, 2010). Elimination of ErbB4 with PV-Cre decreased GABAergic transmission, induced locomotor hyperactivity, and caused impairments in PPI, working memory and fear conditioning (Chen et al, 2010; Wen et al, 2010). Importantly, targeting the ErbB4-signaling pathway with a small-molecule inhibitor of the PI3 kinase improved behavioral phenotypes in two mouse models of schizophrenia-related behavioral deficits, suggesting that ErbB4 signaling could be a medication target for a subset of patients with schizophrenia (Law et al, 2012).
A recent paper used Lhx6-Cre to eliminate ErbB4 expression selectively from MGE-derived LCNs shortly after cell cycle exit (Del Pino et al, 2013). Although the SST-expressing subgroup was not affected, PV-expressing LCNs had a significant reduction of excitatory inputs. In addition to behavioral deficits that phenocopy some aspects of schizophrenia-related cognitive deficits, these mice, with an interneuron-selective loss of ErbB4 function, also showed a marked reduction of dendritic spines on prefrontal cortical pyramidal neurons. As this reduction also phenocopies a frequently reported finding in schizophrenia and related mouse models (Faludi and Mirnics, 2011), this study supports the possibility that interneuron alterations may be causative, rather than downstream (Lewis et al, 2012), of an etiology of schizophrenia. That said, given the heterogeneity of this disorder, etiologies are very likely to occur where LCN dysfunction is downstream of the causative process.
Ventral Hippocampal Hyperactivity
Given the role of GABAergic LCNs, particularly the PV-expressing subgroup, in PFC functions that are frequently found to be disrupted in patients with schizophrenia, it is understandable that most studies on an LCN-related pathophysiology of schizophrenia have focused on the PFC (Lewis et al, 2012). However, a connection between LCN dysfunction and hippocampal abnormalities in schizophrenia bears mention. Psychosis has long been associated with enhanced dopamine signaling in the striatum (Abi-Dargham, 2004; Kellendonk et al, 2009). Multiple lines of evidence indicate that ventral hippocampal activity, via a circuit that includes the nucleus accumbens and ventral tegmentum, enhances striatal release of DA (Lisman et al, 2008). Multiple studies have also documented a remarkable correlation between patients’ report of psychosis and their level of hyperactivation of the ventral hippocampus (Schobel et al, 2013, 2009; Small et al, 2011). These studies raise the possibility that a disease state-producing ventral hippocampal hyperactivation would also produce psychosis. In fact, in contrast to most post-mortem findings in PFC, where PV, GAD67, and other LCN-related measures are reduced but not in a manner consistent with actual cell loss, an excellent study of LCN numbers in hippocampus does report reduced numbers of cortical LCNs (Konradi et al, 2011). Remarkably, in a rodent model that produces, among other abnormalities, a reduction of hippocampal LCNs and enhanced striatal DA release, transplantation of LCN precursors into the adult hippocampus corrected the striatal phenotype and the correlating behavioral abnormality (Perez and Lodge, 2013). This finding has been replicated and extended using a transgenic mouse model, in which there is a developmental loss of PV-expressing LCNs in the hippocampus (Gilani et al, 2014). Hippocampal transplants into adults of LCN precursors enriched for those committed to PV-expressing fates corrected multiple psychosis-related alterations in this model. Some of these corrections include the increased hippocampal blood flow, the increased ventral tegmental DA neuron firing, and the increased locomotor response to amphetamine. These studies suggest that medication development targeting the enhancement of hippocampal LCN function, if not actual transplants in cases of severe treatment resistance with fMRI confirmation of hippocampal hyperactivity, warrants serious consideration (Gill and Grace, 2013).
Summary and Conclusions
Cortical LCN development involves stages of proliferation, nonradial migration, and cortical integration, and disruptions at each of these stages has been associated with neuropsychiatric disorders. At the same time, improved understanding of how embryonic or neonatal insults can result in later manifestations of cortical dysfunction provides the opportunity to devise novel therapies. Although correcting the initial problem as it happens may not be realistic, improved understanding of how these problems relate to later cortical dysfunctions, which may themselves shift throughout the maturation process, can allow us to identify windows of opportunity for interventions intended to balance or normalize the downstream pathological sequelae of earlier insults.
FUNDING AND DISCLOSURE
The authors declare no conflict of interest.
References
Abi-Dargham A (2004). Do we still believe in the dopamine hypothesis? New data bring new evidence. Int J Neuropsychopharmacol 7 (Suppl 1): S1–S5.
Anderson SA, Classey JD, Conde F, Lund JS, Lewis DA (1995). Synchronous development of pyramidal neuron dendritic spines and parvalbumin-immunoreactive chandelier neuron axon terminals in layer III of monkey prefrontal cortex. Neuroscience 67: 7–22.
Anderson SA, Kaznowski CE, Horn C, Rubenstein JL, McConnell SK (2002). Distinct origins of neocortical projection neurons and interneurons in vivo. Cereb Cortex 12: 702–709.
Anderson SA, Marin O, Horn C, Jennings K, Rubenstein JL (2001). Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128: 353–363.
Arguello A, Yang X, Vogt D, Stanco A, Rubenstein JL, Cheyette BN (2013). Dapper antagonist of catenin-1 cooperates with Dishevelled-1 during postsynaptic development in mouse forebrain GABAergic interneurons. PloS One 8: e67679.
Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A et al (2008). Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 9: 557–568.
Au E, Ahmed T, Karayannis T, Biswas S, Gan L, Fishell G (2013). A modular gain-of-function approach to generate cortical interneuron subtypes from ES cells. Neuron 80: 1145–1158.
Azim E, Jabaudon D, Fame RM, Macklis JD (2009). SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nature Neurosci 12: 1238–1247.
Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K et al (2009). Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. Proc Natl Acad Sci USA 106: 4507–4512.
Bartolini G, Ciceri G, Marin O (2013). Integration of GABAergic interneurons into cortical cell assemblies: lessons from embryos and adults. Neuron 79: 849–864.
Bassett AS, Marshall CR, Lionel AC, Chow EW, Scherer SW (2008). Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome. Hum Mol Genet 17: 4045–4053.
Bassett AS, Scherer SW, Brzustowicz LM (2010). Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease. Am J Psychiatry 167: 899–914.
Batista-Brito R, Fishell G (2009). The developmental integration of cortical interneurons into a functional network. Curr Top Dev Biol 87: 81–118.
Batista-Brito R, Rossignol E, Hjerling-Leffler J, Denaxa M, Wegner M, Lefebvre V et al (2009). The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron 63: 466–481.
Bortone D, Polleux F (2009). KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner. Neuron 62: 53–71.
Brown KN, Chen S, Han Z, Lu CH, Tan X, Zhang XJ et al (2011). Clonal production and organization of inhibitory interneurons in the neocortex. Science 334: 480–486.
Buonanno A (2011). The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits. Brain Res Bull 83: 122–131.
Butt SJ, Fuccillo M, Nery S, Noctor S, Kriegstein A, Corbin JG et al (2005). The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron 48: 591–604.
Chen Y-J, Zhang M, Yin D-M, Wen L, Ting A, Wang P et al (2010). ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation. Proc Natl Acad Sci USA 107: 21818–21823.
Close J, Xu H, De Marco Garcia N, Batista-Brito R, Rossignol E, Rudy B et al (2012). Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons. J Neurosci 32: 17690–17705.
Cobos I, Calcagnotto ME, Vilaythong AJ, Thwin MT, Noebels JL, Baraban SC et al (2005). Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nature Neurosci 8: 1059–1068.
Crandall JE, McCarthy DM, Araki KY, Sims JR, Ren JQ, Bhide PG (2007). Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci 27: 3813–3822.
Cuzon VC, Yeh PW, Cheng Q, Yeh HH (2006). Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence. Cereb Cortex 16: 1377–1388.
De Marco Garcia NV, Karayannis T, Fishell G (2011). Neuronal activity is required for the development of specific cortical interneuron subtypes. Nature 472: 351–355.
DeFelipe J, Lopez-Cruz PL, Benavides-Piccione R, Bielza C, Larranaga P, Anderson S et al (2013). New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat Rev Neurosc 14: 202–216.
Del Pino I, Garcia-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martinez de Lagran M et al (2013). Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Neuron 79: 1152–1168.
Du T, Xu Q, Ocbina PJ, Anderson SA (2008). NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development 135: 1559–1567.
Eggan SM, Lazarus MS, Stoyak SR, Volk DW, Glausier JR, Huang ZJ et al (2012). Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia. Biol Psychiatry 71: 114–119.
Faludi G, Mirnics K (2011). Synaptic changes in the brain of subjects with schizophrenia. Int J Dev Neurosci 29: 305–309.
Fazzari P, Paternain AV, Valiente M, Pla R, Lujan R, Lloyd K et al (2010). Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature 464: 1376–1380.
Fertuzinhos S, Krsnik Z, Kawasawa YI, Rasin MR, Kwan KY, Chen JG et al (2009). Selective depletion of molecularly defined cortical interneurons in human holoprosencephaly with severe striatal hypoplasia. Cereb Cortex 19: 2196–2207.
Flames N, Long JE, Garratt AN, Fischer TM, Gassmann M, Birchmeier C et al (2004). Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron 44: 251–261.
Flames N, Pla R, Gelman DM, Rubenstein JL, Puelles L, Marin O (2007). Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci 27: 9682–9695.
Fuccillo M, Rallu M, McMahon AP, Fishell G (2004). Temporal requirement for hedgehog signaling in ventral telencephalic patterning. Development 131: 5031–5040.
Gelman DM, Martini FJ, Nobrega-Pereira S, Pierani A, Kessaris N, Marin O (2009). The embryonic preoptic area is a novel source of cortical GABAergic interneurons. J Neurosci 29: 9380–9389.
Gilani AI, Chohan MO, Inan M, Schobel SA, Chaudhury NH, Paskewitz S et al (2014). Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition. Proc Natl Acad Sci USA 111: 7450–7455.
Gill KM, Grace AA (2013). The role of alpha5 GABAA receptor agonists in the treatment of cognitive deficits in schizophrenia. Curr Pharm Des 20: 5069–5076.
Glickstein SB, Alexander S, Ross ME (2007a). Differences in cyclin D2 and D1 protein expression distinguish forebrain progenitor subsets. Cereb Cortex 17: 632–642.
Glickstein SB, Moore H, Slowinska B, Racchumi J, Suh M, Chuhma N et al (2007b). Selective cortical interneuron and GABA deficits in cyclin D2-null mice. Development 134: 4083–4093.
Golub MS, Germann SL, Lloyd KC (2004). Behavioral characteristics of a nervous system-specific erbB4 knock-out mouse. Behav Brain Res 153: 159–170.
Guo J, Anton ES (2014). Decision making during interneuron migration in the developing cerebral cortex. Trends Cell Biol 24: 342–351.
Hansen DV, Lui JH, Flandin P, Yoshikawa K, Rubenstein JL, Alvarez-Buylla A et al (2013). Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences. Nature Neurosci 16: 1576–1587.
Hebert JM, Fishell G (2008). The genetics of early telencephalon patterning: some assembly required. Nature Rev Neurosci 9: 678–685.
Hensch TK (2005). Critical period plasticity in local cortical circuits. Nature Rev Neurosci 6: 877–888.
Hevner RF, Daza RA, Englund C, Kohtz J, Fink A (2004). Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration. Neuroscience 124: 605–618.
Huang ZJ, Kirkwood A, Pizzorusso T, Porciatti V, Morales B, Bear MF et al (1999). BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98: 739–755.
Inan M, Petros TJ, Anderson SA (2013). Losing your inhibition: linking cortical GABAergic interneurons to schizophrenia. Neurobiol Dis 53: 36–48.
Inan M, Welagen J, Anderson SA (2012). Spatial and temporal bias in the mitotic origins of somatostatin- and parvalbumin-expressing interneuron subgroups and the chandelier subtype in the medial ganglionic eminence. Cereb Cortex 22: 820–827.
Jakovcevski I, Mayer N, Zecevic N (2011). Multiple origins of human neocortical interneurons are supported by distinct expression of transcription factors. Cereb Cortex 21: 1771–1782.
Karayannis T, Au E, Patel JC, Kruglikov I, Markx S, Delorme R et al (2014). Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission. Nature 511: 236–240.
Karayiorgou M, Simon TJ, Gogos JA (2010). 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nature Rev Neurosci 11: 402–416.
Kellendonk C, Simpson EH, Kandel ER (2009). Modeling cognitive endophenotypes of schizophrenia in mice. Trends Neurosci 32: 347–358.
Kepecs A, Fishell G (2014). Interneuron cell types are fit to function. Nature 505: 318–326.
Konradi C, Yang CK, Zimmerman EI, Lohmann KM, Gresch P, Pantazopoulos H et al (2011). Hippocampal interneurons are abnormal in schizophrenia. Schizophr Res 131: 165–173.
Lavdas AA, Grigoriou M, Pachnis V, Parnavelas JG (1999). The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J Neurosci 19: 7881–7888.
Law AJ, Wang Y, Sei Y, O'Donnell P, Piantadosi P, Papaleo F et al (2012). Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110delta inhibition as a potential therapeutic strategy. Proc Natl Acad Sci USA 109: 12165–12170.
Le TN, Du G, Fonseca M, Zhou Q-P, Wigle JT, Eisenstat DD (2007). Dlx homeobox genes promote cortical interneuron migration from the basal forebrain by direct repression of the semaphorin receptor neuropilin-2. J Biol Chem 282: 19071–19081.
Lee S, Hjerling-Leffler J, Zagha E, Fishell G, Rudy B (2010). The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. J Neurosci 30: 16796–16808.
Letinic K, Zoncu R, Rakic P (2002). Origin of GABAergic neurons in the human neocortex. Nature 417: 645–649.
Lewis DA, Curley AA, Glausier JR, Volk DW (2012). Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35: 57–67.
Liodis P, Denaxa M, Grigoriou M, Akufo-Addo C, Yanagawa Y, Pachnis V (2007). Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. J Neurosci 27: 3078–3089.
Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S et al (2008). Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31: 234–242.
Lodato S, Rouaux C, Quast KB, Jantrachotechatchawan C, Studer M, Hensch TK et al (2011a). Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron 69: 763–779.
Lodato S, Tomassy GS, De Leonibus E, Uzcategui YG, Andolfi G, Armentano M et al (2011b). Loss of COUP-TFI alters the balance between caudal ganglionic eminence- and medial ganglionic eminence-derived cortical interneurons and results in resistance to epilepsy. J Neurosci 31: 4650–4662.
Ma T, Wang C, Wang L, Zhou X, Tian M, Zhang Q et al (2013). Subcortical origins of human and monkey neocortical interneurons. Nature Neurosci 16: 1588–1597.
Marin O (2012). Interneuron dysfunction in psychiatric disorders. Nature Rev Neurosci 13: 107–120.
Marin O, Anderson SA, Rubenstein JL (2000). Origin and molecular specification of striatal interneurons. J Neurosci 20: 6063–6076.
MarÃn O, Yaron A, Bagri A, Tessier-Lavigne M, Rubenstein JL (2001). Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science 293: 872–875.
Maynard TM, Gopalakrishna D, Meechan DW, Paronett EM, Newbern JM, LaMantia AS (2013). 22q11 Gene dosage establishes an adaptive range for sonic hedgehog and retinoic acid signaling during early development. Hum Mol Genet 22: 300–312.
Meechan DW, Rutz HL, Fralish MS, Maynard TM, Rothblat LA, Lamantia AS (2013). Cognitive ability is associated with altered medial frontal cortical circuits in the LgDel mouse model of 22q11.2DS. Cereb Cortex (e-pub ahead of print 11 Nov 2013).
Meechan DW, Tucker ES, Maynard TM, Lamantia A-S (2009). Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci USA 106: 16434–16445.
Meechan DW, Tucker ES, Maynard TM, LaMantia A-S (2012a). Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome. Proc Natl Acad Sci 109: 18601–18606.
Meechan DW, Tucker ES, Maynard TM, LaMantia AS (2012b). Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome. Proc Natl Acad Sci USA 109: 18601–18606.
Mei L, Xiong W-C (2008). Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nature Rev Neurosci 9: 437–452.
Miyoshi G, Butt SJ, Takebayashi H, Fishell G (2007). Physiologically distinct temporal cohorts of cortical interneurons arise from telencephalic Olig2-expressing precursors. J Neurosci 27: 7786–7798.
Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa VH, Butt SJ, Battiste J et al (2010). Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J Neurosci 30: 1582–1594.
Murphy KC, Jones LA, Owen MJ (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 56: 940–945.
Neddens J, Fish KN, Tricoire L, Vullhorst D, Shamir A, Chung W et al (2011). Conserved interneuron-specific erbb4 expression in frontal cortex of rodents, monkeys, and humans: implications for schizophrenia. Biol Psychiatry 70: 636–645.
Nery S, Corbin JG, Fishell G (2003). Dlx2 progenitor migration in wild type and nkx2.1 mutant telencephalon. Cereb Cortex 13: 895–903.
Nery S, Fishell G, Corbin JG (2002). The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nature Neurosci 5: 1279–1287.
Nobrega-Pereira S, Kessaris N, Du T, Kimura S, Anderson SA, Marin O (2008). Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors. Neuron 59: 733–745.
Perez SM, Lodge DJ (2013). Hippocampal interneuron transplants reverse aberrant dopamine system function and behavior in a rodent model of schizophrenia. Mol Psychiatry 18: 1193–1198.
Pillai-Nair N, Panicker AK, Rodriguiz RM, Gilmore KL, Demyanenko GP, Huang JZ et al (2005). Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior. J Neurosci 25: 4659–4671.
Pla R, Borrell V, Flames N, Marin O (2006). Layer acquisition by cortical GABAergic interneurons is independent of reelin signaling. J Neurosci 26: 6924–6934.
Polleux F, Whitford KL, Dijkhuizen PA, Vitalis T, Ghosh A (2002). Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling. Development 129: 3147–3160.
Powell EM, Mars WM, Levitt P (2001). Hepatocyte growth factor/scatter factor is a motogen for interneurons migrating from the ventral to dorsal telencephalon. Neuron 30: 79–89.
Pozas E, Ibáñez CF (2005). GDNF and GFRalpha1 promote differentiation and tangential migration of cortical GABAergic neurons. Neuron 45: 701–713.
Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS et al (1994). Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis 182: 476–478.
Rico B, Marin O (2011). Neuregulin signaling, cortical circuitry development and schizophrenia. Curr Opin Genetics Dev 21: 262–270.
Rico B, MarÃn O (2011). Neuregulin signaling, cortical circuitry development and schizophrenia. Curr Opin Genet Dev 21: 262–270.
Rudolph J, Zimmer G, Steinecke A, Barchmann S, Bolz J (2010). Ephrins guide migrating cortical interneurons in the basal telencephalon. Cell Adh Migr 4: 400–408.
Rymar VV, Sadikot AF (2007). Laminar fate of cortical GABAergic interneurons is dependent on both birthdate and phenotype. J Comp Neurol 501: 369–380.
Sanchez-Alcaniz JA, Haege S, Mueller W, Pla R, Mackay F, Schulz S et al (2011). Cxcr7 controls neuronal migration by regulating chemokine responsiveness. Neuron 69: 77–90.
Schobel SA, Chaudhury NH, Khan UA, Paniagua B, Styner MA, Asllani I et al (2013). Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver. Neuron 78: 81–93.
Schobel SA, Lewandowski NM, Corcoran CM, Moore H, Brown T, Malaspina D et al (2009). Differential targeting of the ca1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry 66: 938–946.
Shprintzen RJ, Higgins AM, Antshel K, Fremont W, Roizen N, Kates W (2005). Velo-cardio-facial syndrome. Curr Opin Pediatr 17: 725–730.
Small SA, Schobel SA, Buxton RB, Witter MP, Barnes CA (2011). A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nat Rev Neurosci 12: 585–601.
Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S et al (2002). Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71: 877–892.
Steinecke A, Gampe C, Valkova C, Kaether C, Bolz J (2012). Disrupted-in-schizophrenia 1 (Disc1) is necessary for the correct migration of cortical interneurons. J Neurosci 32: 738–745.
Stumm RK, Zhou C, Ara T, Lazarini F, Dubois-Dalcq M, Nagasawa T et al (2003). CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci 23: 5123–5130.
Sussel L, Marin O, Kimura S, Rubenstein JL (1999). Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development 126: 3359–3370.
Tai Y, Janas Justyna A, Wang C-L, Van Aelst L (2014). Regulation of chandelier cell cartridge and bouton development via Dock7-mediated Erbb4 activation. Cell Rep 6: 254–263.
Taniguchi H, Lu J, Huang ZJ (2013). The spatial and temporal origin of chandelier cells in mouse neocortex. Science 339: 70–74.
Tiveron MC, Rossel M, Moepps B, Zhang YL, Seidenfaden R, Favor J et al (2006). Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone. J Neurosci 26: 13273–13278.
Toritsuka M, Kimoto S, Muraki K, Landek-Salgado MA, Yoshida A, Yamamoto N et al (2013). Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model. Proc Natl Acad Sci USA 110: 17552–17557.
Tricoire L, Pelkey KA, Daw MI, Sousa VH, Miyoshi G, Jeffries B et al (2010). Common origins of hippocampal Ivy and nitric oxide synthase expressing neurogliaform cells. J Neurosci 30: 2165–2176.
Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K (2009). Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron 63: 451–465.
Wang Y, Li G, Stanco A, Long JE, Crawford D, Potter GB et al (2011). CXCR4 and CXCR7 have distinct functions in regulating interneuron migration. Neuron 69: 61–76.
Wen L, Lu Y-S, Zhu X-H, Li X-M, Woo R-S, Chen Y-J et al (2010). Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. Proc Natl Acad Sci USA 107: 1211–1216.
Wonders CP, Anderson SA (2006). The origin and specification of cortical interneurons. Nature Rev Neurosci 7: 687–696.
Wonders CP, Taylor L, Welagen J, Mbata IC, Xiang JZ, Anderson SA (2008). A spatial bias for the origins of interneuron subgroups within the medial ganglionic eminence. Dev Biol 314: 127–136.
Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M (2008). Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 40: 880–885.
Xu Q, Cobos I, De La Cruz E, Rubenstein JL, Anderson SA (2004). Origins of cortical interneuron subtypes. J Neurosci 24: 2612–2622.
Xu Q, Guo L, Moore H, Waclaw RR, Campbell K, Anderson SA (2010a). Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron 65: 328–340.
Xu Q, Wonders CP, Anderson SA (2005). Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon. Development 132: 4987–4998.
Xu X, Roby KD, Callaway EM (2010b). Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells. J Comp Neurol 518: 389–404.
Yang J-M, Zhang J, Chen X-J, Geng H-Y, Ye M, Spitzer NC et al (2013). Development of GABA circuitry of fast-spiking basket interneurons in the medial prefrontal cortex of Erbb4-mutant mice. J Neurosci 33: 19724–19733.
Yu X, Zecevic N (2011). Dorsal radial glial cells have the potential to generate cortical interneurons in human but not in mouse brain. J Neurosci 31: 2413–2420.
Zhu Y, Li H, Zhou L, Wu JY, Rao Y (1999). Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex. Neuron 23: 473–485.
Zimmer G, Garcez P, Rudolph J, Niehage R, Weth F, Lent R et al (2008). Ephrin-A5 acts as a repulsive cue for migrating cortical interneurons. Eur J Neurosci 28: 62–73.
Acknowledgements
This study was funded by NIMH (SA, R01 MH066912).
Author information
Authors and Affiliations
Corresponding author
PowerPoint slides
Rights and permissions
About this article
Cite this article
Chu, J., Anderson, S. Development of Cortical Interneurons. Neuropsychopharmacol 40, 16–23 (2015). https://doi.org/10.1038/npp.2014.171
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/npp.2014.171
This article is cited by
-
Differential vulnerability of anterior cingulate cortex cell types to diseases and drugs
Molecular Psychiatry (2022)
-
Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders
Molecular Psychiatry (2019)
-
Cortical interneuron function in autism spectrum condition
Pediatric Research (2019)
-
Common basis for orofacial clefting and cortical interneuronopathy
Translational Psychiatry (2018)
-
Neuroanatomical and molecular correlates of cognitive and behavioural outcomes in hypogonadal males
Metabolic Brain Disease (2018)