Figure 1 - uploaded by Tania Vitalis
Content may be subject to copyright.
Cortical development. Schematic drawings of coronal sections of the developing mouse cortex. Afferent axons and the migration of telencephalic interneurons from the basal telencephalon are drawn in purple and black respectively. Cortical development begins with the appearance of a population of cells along the lateral ventricle, known as the ventricular zone (E11; VZ). This population of cells gives rise to most of the neurons and glial cells of the cerebral cortex. Once generated, neurons migrate towards the pial surface and complete their differentiation in the cortical plate. Neurons that will populate the deeper layers of the cortex are generated and then migrate away form the VZ earlier than the neurons that will populate progressively more superficial layers. On E12-E13, the cerebral wall is bilaminar consisting of the VZ and overlying primitive preplate. By E17-E18 the thickness of the overlying intermediate zone/with matter and developing cortical plate are at their maximum widths, with all neuronal cells having exited the cell cycle and migrated to their final laminar distribution within the developing cortex. CP, cortical plate; IZ, intermediate zone; MZ, marginal zone; PP, preplate; SP, subplate; TC, thalamocortical axons; SVZ, subventricular zone.
Source publication
The concerted development of GABAergic interneurons and glutamatergic neurons is a key feature in the construction of the cerebral cortex. In contrast with glutamatergic neurons, GABAergic interneurons are heterogeneous differing by their axonal and dendritic morphologies, biochemical markers, connectivity, and physiology. Furthermore, interneurons...
Contexts in source publication
Context 1
... and physiology (DeFelipe, 1993; Cauli et al., 1997; Gupta et al., 2000; Kawaguchi and Kondo, 2002; Ascoli et al., 2008). Cajal was the first neuroscientist to discover the morphological diversity of interneurons cell bodies and dendrites in the cerebral cortex. Already at that time his drawings with those of his student Lorente de No have described their rich axonal arborisation, giving addi- tional features to distinguish several types of interneurons. More recently, the use of electron micros- copy has shown that different types of interneurons target different parts of excitatory and inhibitory synapses (Somogyi and Klausberger, 2005). Using a combination of intracellular recoding, dye filling, single cell RT-PCR and immunostaining with various antibodies against calcium binding proteins and neuropeptides several groups have shown that mor- phologically distinct interneurons exhibit different firing pattern and express different sets of molecular markers (Cauli et al., 1997; Gonchar and Burkhalter, 1997; Kawaguchi and Kubota, 1996, 1997; Gupta et al., 2000; Markram et al., 2004; review in Burkhalter, 2008). The first meeting on interneurons classification was held in Cajal’s native village: \ Petilla de Aragon " (Ascoli et al., 2008; The PING group). At that meeting, it was proposed that description of one interneuron class should rely on a combination of features belonging to three categories: morphological, molecular, and physiological. In this review, we will describe particularly the four main types of interneurons populating the somatosensory cortex (see Table 1). Fast-spiking (FS)-cells are the largest and best defined subtype of GABAergic interneurons and are most numerous in Layer IV (Kawaguchi and Kubota, 1997). They fire action potentials at sustained high frequency, have low input resistance, and express Parvalbumin (Parv). They receive strong thalamic input and target pyramidal cell’s somata (in that case they will get the name of basket cells) or initial axonic segment and will in that case get the name of chandelier). They are able to exert a powerful control of the pattern and timing of firing in excitatory pyramidal cells (Sun et al., 2006, Szabadics et al., 2006). They act as an inhibitory gate for incoming sensory information by carrying out feed-forward disynaptic inhibition on the cortical excitatory neurons which are monosynaptically excited by thalamus afferent (Inoue and Imoto, 2006; Sun et al., 2006). these SOM-expressing interneurons reside in all cortical layers except Layer I and have axons that project upward into the layer I. They receive little thalamic input, display adapting action potential discharge and target distant dendrites on both the shaft and spines receiving thalamic inputs. These properties are well- suited for sustained, activity-dependent, control of dendritic integration through local feedback inhibition (Karube et al., 2004). These adapting cells exhibit bipolar somatodendritic morphology with descending axonal arborization. VIP cells preferentially target interneurons and receive direct input from the thalamus. Furthermore, they are able to dilate intracortical blood vessels via the release of VIP. These adapting cells are mainly segregated in the superficial layers and in particular in the Layer I. They are responsible for the slow GABAergic inhibition of pyramidal cells and interneurons (Olah et al., 2009). Neurogliaform cells display axons ramified in all direction, they are also characterized by their high expression of NPY and nitric oxide synthase (NOS), two vasoactive substances. At Petilla meeting important developmental features such as time of genesis (corresponding to the time when an interneuron precursor became postmitotic) and place of genesis were not taken enough into account. Since then several laboratories have now described that interneurons sharing similar morphologies and physiological properties are also sharing similar developmental features: same origin in place and time. An important point of this review is our discussion on whether interneurons are completely specified after their final divisions and how the target tissues contribute in determining their final physiological properties. The cerebral cortex develops from the rostral part of the neural tube named the telencephalic pallium. The wall of the pallium is initially formed of neuroepithe- lial germinal cells whose continued proliferation causes the outward bulging of the pallial walls to form the cerebral vesicles. In rodents, pyramidal and nonpyramidal neurons originate from different regions of the telencephalon. Pyramidal neurons are generated in the cortical ventricular zone (VZ) and follow a \ conventional scheme of inside-out cortical formation " , early postmitotic neurons migrate radi- ally away from the VZ towards the surface of the cerebral vesicles to form the primordial plexiform layer or preplate (PP) (Boulder Committee, 1970; Uylings et al., 1990; Fig. 1). The later-generated neurons migrate to form a layer within the PP, the so-called cortical plate (CP), thus splitting it into a superficial marginal zone (MZ; Layer I) and a deep subplate (SP). The neurons of the CP assemble into Layers II– VI in an \ inside-out " sequence: the deepest cellular layers are assembled first and those closest to the surface last (Bayer and Altman, 1991; Fig. 1). In rodents, numerous studies have demonstrated that telencephalic interneurons derive mainly from the anlagen of the basal telencephalon: the ganglionic eminences (see Fig. 2). In vitro studies of the migration of cortical interneurons (Lavdas et al., 1999; Wichterle et al., 1999) and their fate-mapping (Xu et al., 2004) have shown that the medial ganglionic eminence (MGE) is the principal sources of cortical interneurons expressing SOM and Parv at mature stage (review in Wonders and Anderson, 2006). Recently, grafting experiments have refined this analysis showing that fast-spiking Parv+ interneurons are preferentially generated by the ventral part of the me- dian ganglionic eminence (MGEv) while the dorsal part of the MGE (MGEd) is preferentially giving rise to SOM+ interneurons with bursting firing that accommodates following repetitive firing (Butt et al., 2005; Wonders et al., 2008). More recently, the caudal ganglionic eminence (CGE) has been shown to generate cortical interneurons expressing VIP, VIP/ CR, VIP/CCK, NPY/CR at mature stage (Yozu et al., 2004; Butt et al., 2005; Vucurovic et al., in press; Supporting Information Fig. S1). In addition, we have recently found that CGE produces multipolar NPY+ interneurons that may correspond to neurogliaform interneurons according to their complex axonal morphology and their adapting firing (Vucurovic et al., in press). Using various Cre mouse lines the dual origin of CR+ interneurons has also been demonstrated by Fogarty et al. (2007). Interneurons expressing CR and SOM originate in the MGE while interneurons expressing CR with VIP or CCK originate in the CGE (Fogarty et al., 2007). Interestingly, two independent studies using double- and triple-immunolab- elings have confirmed that mouse interneurons expressing CR are able to express such combination of markers (Gonchar et al., 2008; Xu et al., 2010). Surprisingly, the fate of cells from the LGE, the region of the ganglionic eminence suspected origi- nally to give rise to cortical interneurons has not yet been clearly analyzed (Wichterle et al., 1999). Other reports have also indicated that cortical interneurons are not only generated in the ganglionic eminences but also in the entopeduncular and preoptic areas (AEP/PO) and the cortex. The entopeduncular region is known to generate a transient population of cortical oligodendrocytes (Tekki-Kessaris et al., 2001). More recently this region has also been shown to generate cortical interneurons. Homo- chronic grafting of preoptic territories (and possibly of AEP; our own observation), as well as genetic fate- mapping experiments, have revealed that progenitors expressing the transcription factor NKx5.1 generate NPY/neurogliaform interneurons (Gelman et al., 2009). Despite their different places of origin (AEP/ PO and CGE) neurogliaform interneurons expressing NPY \ only " (with the exclusion of markers classi- cally used for interneurons classification) represent a specific class of interneurons displaying specific physiological functions with their adapting firing (see above; Table 1). By contrast, NPY has been shown in several studies to be associated with SOM, CR, and/ or VIP both at protein or mRNA level. In a recent study using firing pattern and single cell RT-PCR combined with statistical methods to classify rat cortical interneurons Karagiannis et al. have shown that all classes of interneurons are able to express NPY therefore pointing to the nonrelevance of this marker to classify interneurons (Karagiannis et al., 2009). Parallely, NPY is known to be induced in epileptic states and may be \ latent " in various types of interneurons. Indeed, while cultured in specific medium all interneurons appear to be able to expressed NPY (Wirth et al., 2005). Very recently, a study has shown that a small frac- tion of cortical CR+ interneurons preferentially located in the lower cortical layers is generated within the cortical subventricular zone at early postnatal stages (Inta et al., 2008; see also Cameron and Dayer, 2008). This last point is interesting regarding evolution. Indeed, in Primates interneurons arise from both the cortical VZ/SVZ and the ganglionic eminence. By analyzing the development of normal and holoprosencephalic human brains, several studies have strongly suggested that CR interneurons (a pre- dominant population of interneurons in the human cortex) would be preferentially generated in the cerebral cortex while other subtypes would preferentially be generated in the ganglionic eminences (Letinic et al., 2002; review in Rakic, 2009). ...
Context 2
... giving addi- tional features to distinguish several types of interneurons. More recently, the use of electron micros- copy has shown that different types of interneurons target different parts of excitatory and inhibitory synapses (Somogyi and Klausberger, 2005). Using a combination of intracellular recoding, dye filling, single cell RT-PCR and immunostaining with various antibodies against calcium binding proteins and neuropeptides several groups have shown that mor- phologically distinct interneurons exhibit different firing pattern and express different sets of molecular markers (Cauli et al., 1997; Gonchar and Burkhalter, 1997; Kawaguchi and Kubota, 1996, 1997; Gupta et al., 2000; Markram et al., 2004; review in Burkhalter, 2008). The first meeting on interneurons classification was held in Cajal’s native village: \ Petilla de Aragon " (Ascoli et al., 2008; The PING group). At that meeting, it was proposed that description of one interneuron class should rely on a combination of features belonging to three categories: morphological, molecular, and physiological. In this review, we will describe particularly the four main types of interneurons populating the somatosensory cortex (see Table 1). Fast-spiking (FS)-cells are the largest and best defined subtype of GABAergic interneurons and are most numerous in Layer IV (Kawaguchi and Kubota, 1997). They fire action potentials at sustained high frequency, have low input resistance, and express Parvalbumin (Parv). They receive strong thalamic input and target pyramidal cell’s somata (in that case they will get the name of basket cells) or initial axonic segment and will in that case get the name of chandelier). They are able to exert a powerful control of the pattern and timing of firing in excitatory pyramidal cells (Sun et al., 2006, Szabadics et al., 2006). They act as an inhibitory gate for incoming sensory information by carrying out feed-forward disynaptic inhibition on the cortical excitatory neurons which are monosynaptically excited by thalamus afferent (Inoue and Imoto, 2006; Sun et al., 2006). these SOM-expressing interneurons reside in all cortical layers except Layer I and have axons that project upward into the layer I. They receive little thalamic input, display adapting action potential discharge and target distant dendrites on both the shaft and spines receiving thalamic inputs. These properties are well- suited for sustained, activity-dependent, control of dendritic integration through local feedback inhibition (Karube et al., 2004). These adapting cells exhibit bipolar somatodendritic morphology with descending axonal arborization. VIP cells preferentially target interneurons and receive direct input from the thalamus. Furthermore, they are able to dilate intracortical blood vessels via the release of VIP. These adapting cells are mainly segregated in the superficial layers and in particular in the Layer I. They are responsible for the slow GABAergic inhibition of pyramidal cells and interneurons (Olah et al., 2009). Neurogliaform cells display axons ramified in all direction, they are also characterized by their high expression of NPY and nitric oxide synthase (NOS), two vasoactive substances. At Petilla meeting important developmental features such as time of genesis (corresponding to the time when an interneuron precursor became postmitotic) and place of genesis were not taken enough into account. Since then several laboratories have now described that interneurons sharing similar morphologies and physiological properties are also sharing similar developmental features: same origin in place and time. An important point of this review is our discussion on whether interneurons are completely specified after their final divisions and how the target tissues contribute in determining their final physiological properties. The cerebral cortex develops from the rostral part of the neural tube named the telencephalic pallium. The wall of the pallium is initially formed of neuroepithe- lial germinal cells whose continued proliferation causes the outward bulging of the pallial walls to form the cerebral vesicles. In rodents, pyramidal and nonpyramidal neurons originate from different regions of the telencephalon. Pyramidal neurons are generated in the cortical ventricular zone (VZ) and follow a \ conventional scheme of inside-out cortical formation " , early postmitotic neurons migrate radi- ally away from the VZ towards the surface of the cerebral vesicles to form the primordial plexiform layer or preplate (PP) (Boulder Committee, 1970; Uylings et al., 1990; Fig. 1). The later-generated neurons migrate to form a layer within the PP, the so-called cortical plate (CP), thus splitting it into a superficial marginal zone (MZ; Layer I) and a deep subplate (SP). The neurons of the CP assemble into Layers II– VI in an \ inside-out " sequence: the deepest cellular layers are assembled first and those closest to the surface last (Bayer and Altman, 1991; Fig. 1). In rodents, numerous studies have demonstrated that telencephalic interneurons derive mainly from the anlagen of the basal telencephalon: the ganglionic eminences (see Fig. 2). In vitro studies of the migration of cortical interneurons (Lavdas et al., 1999; Wichterle et al., 1999) and their fate-mapping (Xu et al., 2004) have shown that the medial ganglionic eminence (MGE) is the principal sources of cortical interneurons expressing SOM and Parv at mature stage (review in Wonders and Anderson, 2006). Recently, grafting experiments have refined this analysis showing that fast-spiking Parv+ interneurons are preferentially generated by the ventral part of the me- dian ganglionic eminence (MGEv) while the dorsal part of the MGE (MGEd) is preferentially giving rise to SOM+ interneurons with bursting firing that accommodates following repetitive firing (Butt et al., 2005; Wonders et al., 2008). More recently, the caudal ganglionic eminence (CGE) has been shown to generate cortical interneurons expressing VIP, VIP/ CR, VIP/CCK, NPY/CR at mature stage (Yozu et al., 2004; Butt et al., 2005; Vucurovic et al., in press; Supporting Information Fig. S1). In addition, we have recently found that CGE produces multipolar NPY+ interneurons that may correspond to neurogliaform interneurons according to their complex axonal morphology and their adapting firing (Vucurovic et al., in press). Using various Cre mouse lines the dual origin of CR+ interneurons has also been demonstrated by Fogarty et al. (2007). Interneurons expressing CR and SOM originate in the MGE while interneurons expressing CR with VIP or CCK originate in the CGE (Fogarty et al., 2007). Interestingly, two independent studies using double- and triple-immunolab- elings have confirmed that mouse interneurons expressing CR are able to express such combination of markers (Gonchar et al., 2008; Xu et al., 2010). Surprisingly, the fate of cells from the LGE, the region of the ganglionic eminence suspected origi- nally to give rise to cortical interneurons has not yet been clearly analyzed (Wichterle et al., 1999). Other reports have also indicated that cortical interneurons are not only generated in the ganglionic eminences but also in the entopeduncular and preoptic areas (AEP/PO) and the cortex. The entopeduncular region is known to generate a transient population of cortical oligodendrocytes (Tekki-Kessaris et al., 2001). More recently this region has also been shown to generate cortical interneurons. Homo- chronic grafting of preoptic territories (and possibly of AEP; our own observation), as well as genetic fate- mapping experiments, have revealed that progenitors expressing the transcription factor NKx5.1 generate NPY/neurogliaform interneurons (Gelman et al., 2009). Despite their different places of origin (AEP/ PO and CGE) neurogliaform interneurons expressing NPY \ only " (with the exclusion of markers classi- cally used for interneurons classification) represent a specific class of interneurons displaying specific physiological functions with their adapting firing (see above; Table 1). By contrast, NPY has been shown in several studies to be associated with SOM, CR, and/ or VIP both at protein or mRNA level. In a recent study using firing pattern and single cell RT-PCR combined with statistical methods to classify rat cortical interneurons Karagiannis et al. have shown that all classes of interneurons are able to express NPY therefore pointing to the nonrelevance of this marker to classify interneurons (Karagiannis et al., 2009). Parallely, NPY is known to be induced in epileptic states and may be \ latent " in various types of interneurons. Indeed, while cultured in specific medium all interneurons appear to be able to expressed NPY (Wirth et al., 2005). Very recently, a study has shown that a small frac- tion of cortical CR+ interneurons preferentially located in the lower cortical layers is generated within the cortical subventricular zone at early postnatal stages (Inta et al., 2008; see also Cameron and Dayer, 2008). This last point is interesting regarding evolution. Indeed, in Primates interneurons arise from both the cortical VZ/SVZ and the ganglionic eminence. By analyzing the development of normal and holoprosencephalic human brains, several studies have strongly suggested that CR interneurons (a pre- dominant population of interneurons in the human cortex) would be preferentially generated in the cerebral cortex while other subtypes would preferentially be generated in the ganglionic eminences (Letinic et al., 2002; review in Rakic, 2009). Mature Parv+ and SOM+ interneurons located preferentially in the deep cortical lamina are born (Parv+: E9.5-E15; SOM+: E9.5-E14) before the vast majority of VIP+, NPY+ interneurons. Most of the bipolar- and double bouquet- CR+ interneurons preferentially located in the superficial layers are generated between E12.5 and E15.5. (Rymar and Sadikot, 2007; review in Butt et al., 2007). Birthdating ...
Similar publications
In the cerebral cortex, GABAergic interneurons have evolved as a highly heterogeneous collection of cell types that are characterized by their unique spatial and temporal capabilities to influence neuronal circuits. Current estimates suggest that up to 50 different types of GABAergic neurons may populate the cerebral cortex, all derived from progen...
Gamma-aminobutyric acid neurons, born in remote germinative zones in the ventral forebrain (telencephalon), migrate tangentially in two spatially distinct streams to adopt their specific positions in the developing cortex. The cell types and molecular cues that regulate this divided migratory route remains to be elucidated. Here we show that embryo...
Citations
... In mammals, during early cortical development and up to 16 weeks of gestation (GW16), 5-HT is of maternal and/or placental origin (Cote et al., 2007;Bonnin and Levitt, 2011;Beopoulos et al., 2022), whereas later, serotonergic afferents invade the cortex and the developing fetus initiates its own 5-HT production (Gaspar et al., 2003;Vitalis and Rossier, 2011;Budday et al., 2015;Nowakowski et al., 2016;Beopoulos et al., 2022). Importantly, 5-HT signaling is influenced by numerous epigenetic and genetic factors, as well as by perinatal stress (Papaioannou et al., 2002;Provenzi et al., 2016), infection and inflammation (Winter et al., 2009;Gupta et al., 2015), 5-HT metabolism and storage, (Popa et al., 2008) and genetic alterations (Pluess et al., 2010;Karg et al., 2011). ...
Autism spectrum disorders (ASDs) are perhaps the most severe, intractable and challenging child psychiatric disorders. They are complex, pervasive and highly heterogeneous and depend on multifactorial neurodevelopmental conditions. Although the pathogenesis of autism remains unclear, it revolves around altered neurodevelopmental patterns and their implications for brain function, although these cannot be specifically linked to symptoms. While these affect neuronal migration and connectivity, little is known about the processes that lead to the disruption of specific laminar excitatory and inhibitory cortical circuits, a key feature of ASD. It is evident that ASD has multiple underlying causes and this multigenic condition has been considered to also dependent on epigenetic effects, although the exact nature of the factors that could be involved remains unclear. However, besides the possibility for differential epigenetic markings directly affecting the relative expression levels of individual genes or groups of genes, there are at least three mRNA epitranscriptomic mechanisms, which function cooperatively and could, in association with both genotypes and environmental conditions, alter spatiotemporal proteins expression patterns during brain development, at both quantitative and qualitative levels, in a tissue-specific, and context-dependent manner. As we have already postulated, sudden changes in environmental conditions, such as those conferred by maternal inflammation/immune activation, influence RNA epitranscriptomic mechanisms, with the combination of these processes altering fetal brain development. Herein, we explore the postulate whereby, in ASD pathogenesis, RNA epitranscriptomics might take precedence over epigenetic modifications. RNA epitranscriptomics affects real-time differential expression of receptor and channel proteins isoforms, playing a prominent role in central nervous system (CNS) development and functions, but also RNAi which, in turn, impact the spatiotemporal expression of receptors, channels and regulatory proteins irrespective of isoforms. Slight dysregulations in few early components of brain development, could, depending upon their extent, snowball into a huge variety of pathological cerebral alterations a few years after birth. This may very well explain the enormous genetic, neuropathological and symptomatic heterogeneities that are systematically associated with ASD and psychiatric disorders at large.
... Whereas Sst + neurons are produced during the early stage of neurogenesis, a large proportion of the Pvalb + neurons are generated in the MGE during the late stages (Rymar and Sadikot, 2007). On the other hand, the CGEderived GABAergic neurons are produced in late embryonic stages and mainly express either Reln or Vip (Nery et al., 2002;Miyoshi et al., 2010;Rudy et al., 2011;Vitalis and Rossier, 2011). Reln + neurons are derived from both the CGE and MGE, as subpopulations of the MGE-derived Sst + neurons coexpress Reln (Miyoshi et al., 2010;Miyoshi and Fishell, 2011). ...
Intermediate progenitors of both excitatory and inhibitory neurons, which can replenish neurons in the adult brain, were recently identified. However, the generation of intermediate progenitors of GABAergic inhibitory neurons (IPGNs) has not been studied in detail. Here, we characterized the spatiotemporal distribution of IPGNs in mouse cerebral cortex. IPGNs generated neurons during both embryonic and postnatal stages, but the embryonic IPGNs were more proliferative. Our lineage tracing analyses showed that the embryonically proliferating IPGNs tended to localize to the superficial layers rather than the deep cortical layers at 3 weeks after birth. We also found that embryonic IPGNs derived from the medial and caudal ganglionic eminence (CGE) but more than half of the embryonic IPGNs were derived from the CGE and broadly distributed in the cerebral cortex. Taken together, our data indicate that the broadly located IPGNs during embryonic and postnatal stages exhibit a different proliferative property and layer distribution.
... The reduced number of NPY-IR cells could therefore be related to cell loss. On the other hand, NPY-expression is known to be induced by neuronal activity (Marty, 2000) and it has been proposed that it could be "latent" in various types of interneurons (Vitalis and Rossier, 2011). For this reason, the reduced number of NPY-IR neurons could also be related to a reduced expression of the peptide. ...
Hippocampal dysfunction plays a central role in neurodevelopmental disorders, resulting in severe impairment of cognitive abilities, including memory and learning. On this basis, developmental studies represent an important tool both to understanding the cellular and molecular phenomena underlying early hippocampal damage and to study possible therapeutic interventions, that may modify the progression of neuronal death. Given the modulatory role played by 17β-estradiol (E2) on hippocampal functions and its neuroprotective properties, the present study investigates the effects of pretreatment with E2 in a model of neonatal hippocampal injury obtained by trimethyltin (TMT) administration, characterized by neuronal loss in CA1 and CA3 subfields and astroglial and microglial activation. At post-natal days (P)5 and P6 animals received E2 administration (0.2 mg/kg/die i.p.) or vehicle. At P7 they received a single dose of TMT (6.5 mg/kg i.p.) and were sacrificed 72 h (P10) or 7 days after TMT treatment (P14). Our findings indicate that pretreatment with E2 exerts a protective effect against hippocampal damage induced by TMT administration early in development, reducing the extent of neuronal death in the CA1 subfield, inducing the activation of genes involved in neuroprotection, lowering the neuroinflammatory response and restoring neuropeptide Y- and parvalbumin- expression, which is impaired in the early phases of TMT-induced damage. Our data support the efficacy of estrogen-based neuroprotective approaches to counteract early occurring hippocampal damage in the developing hippocampus.
... We did not observe any TRPC1 expression in PVALB-ir cells at any cortical layer. PVALB is a calcium-binding protein present in 40%-50% of GABAergic interneurons (Gonchar et al., 2008;Uematsu et al., 2008;Xu et al., 2010) and is commonly expressed in fast spiking chandelier and large basket cells (for a review see DeFelipe, 1997;Markram et al., 2004;Vitalis and Rossier, 2011). Regarding CALR, the colocalization with TRPC1 was modest, but somewhat more abundant at upper layers. ...
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain. The aim of our study was to analyze the neuroanatomical distribution of TRPC1 in the rat neocortex. By double- and triple-labeling and confocal microscopy, we tested the presence of TRPC1 by using a series of specific neurochemical markers. TRPC1 was abundant in SMI 32-positive pyramidal neurons, and in some glutamic acid decarboxylase 67 (GAD67) interneurons, but was lacking in glial fibrillary acidic protein (GFAP)-positive glial cells. In neurons it colocalized with postsynaptic marker MAP2 in cell bodies and apical dendritic trunks and it was virtually absent in synaptophysin-immunoreactive terminals. By using a panel of antibodies to classify interneurons, we identified the GABAergic interneurons that contained TRPC1. TRPC1 was lacking in basket and chandelier parvalbumin (PVALB) cells, and a very low percentage of calretinin (CALR) or calbindin (CALB) interneurons expressed TRPC1. Moreover, 63% of somatostatin (SST) expressing-cells and 37% of reelin-positive cells expressed TRPC1. All the SST/TRPC1 double-labeled cells, many of which were presumptive Martinotti cells (MC), were positive for reelin. The presence of TRPC1 in the somata and apical dendritic trunks of neocortical pyramidal cells suggests a role for this channel in sensory processing and synaptic plasticity. Conversely in SST/reelin interneurons, TRPC1 could modulate GABAergic transmission, which is responsible for shaping the coordinated activity of the pyramidal cells in the cortical network. In future studies, it would be relevant to investigate whether TRPC1 could be involved in the expression or processing of reelin in SST inhibitory interneurons.
... Origins of the Many Classes of GABAergic Cortical Interneurones (Meyer and Wahle, 1988;Wonders and Anderson, 2006;Batista-Brito and Fishell, 2009;Vitalis and Rossier, 2011;Miyoshi et al., 2013;Li and Pleasure, 2014;Wamsley and Fishell, 2017, for reviews;Yavorska and Wehr, 2016 In humans, 65% of neocortical interneurones develop from Mash1-expressing progenitor cells of the VZ and SVC. Mash1 is a gene responsible for differentiation of GABAergic neurones and is also expressed in the subpallium (Letinic et al., 2002;Jakovcevski et al., 2011). ...
Studying neocortex and hippocampus in parallel, we are struck by the similarities. All three to four layered allocortices and the six layered mammalian neocortex arise in the pallium. All receive and integrate multiple cortical and subcortical inputs, provide multiple outputs and include an array of neuronal classes. During development, each cell positions itself to sample appropriate local and distant inputs and to innervate appropriate targets. Simpler cortices had already solved the need to transform multiple coincident inputs into serviceable outputs before neocortex appeared in mammals. Why then do phylogenetically more recent cortices need multiple pyramidal cell layers? A simple answer is that more neurones can compute more complex functions. The dentate gyrus and hippocampal CA regions—which might be seen as hippocampal antecedents of neocortical layers—lie side by side, albeit around a tight bend. Were the millions of cells of rat neocortex arranged in like fashion, the surface area of the CA pyramidal cell layers would be some 40 times larger. Even if evolution had managed to fold this immense sheet into the space available, the distances between neurones that needed to be synaptically connected would be huge and to maintain the speed of information transfer, massive, myelinated fiber tracts would be needed. How much more practical to stack the “cells that fire and wire together” into narrow columns, while retaining the mechanisms underlying the extraordinary precision with which circuits form. This demonstrably efficient arrangement presents us with challenges, however, not the least being to categorize the baffling array of neuronal subtypes in each of five “pyramidal layers.” If we imagine the puzzle posed by this bewildering jumble of apical dendrites, basal dendrites and axons, from many different pyramidal and interneuronal classes, that is encountered by a late-arriving interneurone insinuating itself into a functional circuit, we can perhaps begin to understand why definitive classification, covering every aspect of each neurone's structure and function, is such a challenge. Here, we summarize and compare the development of these two cortices, the properties of their neurones, the circuits they form and the ordered, unidirectional flow of information from one hippocampal region, or one neocortical layer, to another.
... At the onset of cortical development, 5-HT is of maternal and placental origin [17][18][19]. Later, by embryonic day 16 (E16 in mice) [15,16,20] and by gestational week 16 (GW16 in human) [13,14], serotoninergic afferents invade the cerebral cortex and contribute to provide 5-HT locally. Not surprisingly, like in non-mammalian species, serotonin modulates neuronal proliferation, migration and differentiation. ...
... Second, adapting Martinotti cells expressing somatostatin (SOM) that control dendritic information through local feedback inhibition [50]. Third, adapting bipolar interneurons expressing mainly the vasoactive intestinal peptide (VIP) and calretinin (CR) that preferentially target other interneurons and receive direct input from the thalamus [20,51,52]. Fourth, adapting neurogliaform interneurons expressing vasoactive substances, notably the neuropeptide Y (NPY) and/or nitric oxide (NO) that are responsible for the slow GABAergic inhibition of pyramidal cells and interneurons and vasomotion [53][54][55][56]. ...
... In rodent, the cortical GABAergic interneurons are generated outside the cortical VZ, in the subpallium: mainly in the medial ganglionic eminence (MGE) (E11-E14 in mice) and the caudal ganglionic eminence (CGE) (E14-E17 in mice) [11,20,52]. These regions are specified through a combination of distinct transcription factors and morphogenes that produce different classes of interneurons [80]. ...
The mammalian cerebral cortex is critical for sensory and motor integrations and, for higher-order cognitive functions. The construction of mammalian cortical circuits involves the coordinated interplay between cellular processes such as proliferation, migration and differentiation of neural and glial cell subtypes followed by accurate connectivity evolving in complexity in primates. Alteration in cortical development may induce the emergence of various pathological traits and behaviours. Among the large array of factors that regulate the assembly of cortical circuits, serotonin (5-HT) plays important role as a developmental signal that impacts on a broad diversity of cellular processes. 5-HT plays distinct roles during specific sensitive periods and is produced from various sources depending on the perinatal stage. Its roles are mediated by more than fourteen 5-HT receptors that are all G-protein coupled receptors except the ionotropic 5-HT type 3A receptor (5-HT3A) mediating rapid neuronal activation. Importantly, 5-HT metabolism and signalling are influenced by numerous epigenetic and genetic factors, including nutrition and gut microbiota, perinatal stress, infection and inflammation. In this review, we will recapitulate some evidences showing that dysregulation of 5-HT homeostasis and 5-HT3A signalling impairs distinct steps of cortical circuit formation leading to the predisposition of the onset of various psychiatric diseases.
... Here we only touched upon the rapidly evolving field of interneuron diversity being brought about by different progenitor domains and progenitor types and will completely ignore the emerging complexity in the specification of these cells, mostly by molecular mechanism (Kelsom and Lu, 2013;Marı´n and Mu¨ller, 2014). For these and other developmental issues we refer to several published reviews (Flames and Marı´n, 2005;Wonders and Anderson, 2006;Corbin and Butt, 2011;Vitalis and Rossier, 2011;Kepecs and Fishell, 2014). In the context of the present review, our main point is to stress that classifying GABAergic interneurons according to neurochemical/molecular markers has a correlate in developmental processes, which together suggest that there is a finite number of cell types whose specific features are likely to be further diversified in a use-or activity-dependent manner (Garcı´a et al., 2011). ...
Recent years have seen substantial progress in studying the structural and function properties of GABAergic interneurons and their roles in the neuronal networks of barrel cortex. Although GABAergic interneurons represent only about 12% of the total number of neocortical neurons, they are extremely diverse with respect to their structural and functional properties. It has become clear that barrel cortex interneurons not only serve the maintenance of an appropriate excitation/inhibition balance but also are directly involved in sensory processing. In this review we present different interneuron types and their axonal projection pattern framework in the context of the laminar and columnar organisation of the barrel cortex. The main focus is here on the most prominent interneuron types, i.e. basket cells, chandelier cells, Martinotti cells, bipolar/bitufted cells and neurogliaform cells, but interneurons with more unusual axonal domains will also be mentioned. We describe their developmental origin, their classification with respect to molecular, morphological and intrinsic membrane and synaptic properties. Most importantly, we will highlight the most prominent circuit motifs these interneurons are involved in and in which way they serve feed-forward inhibition, feedback inhibition and disinhibition. Finally, this will be put into context to their functional roles in sensory signal perception and processing in the whisker system and beyond.
... Reflecting their various functions, the cortical interneuron population is extraordinarily diverse and can be characterized by multiple measures. These include the expression profile of calcium binding proteins parvalbumin (PV), calbindin (CB), calretinin (CR), and neuropeptides somatostatin (SST), neuropeptide-Y (NPY), vasoactive intestinal polypeptide (VIP), their morphology, site of synapse formation, and electrophysiological properties [2][3][4]. ...
Loss or damage of cortical inhibitory interneurons characterizes a number of neurological disorders. There is therefore a great deal of interest in learning how to generate these neurons from a pluripotent stem cell source so they can be used for cell replacement therapies or for in vitro drug testing. To design a directed differentiation protocol, a number of groups have used the information gained in the last 15 years detailing the conditions that promote interneuron progenitor differentiation in the ventral telencephalon during embryogenesis. The use of Hedgehog peptides and agonists is featured prominently in these approaches. We review here the data documenting a role for Hedgehog in specifying interneurons in both the embryonic brain during development and in vitro during the directed differentiation of pluripotent stem cells.
... Cortical interneurons are clinically relevant; their dysfunction has been implicated in a variety of neurological disorders, including schizophrenia and epilepsy (Benes and Berretta, 2001;Chu and Anderson, 2015;Daskalakis et al., 2007;Di Cristo, 2007;Levitt et al., 2004;Lewis et al., 2012;Marin, 2012). Diverse subgroups of interneurons have been identified on the basis of their morphology, electrophysiological characteristics, embryonic origin, and molecular and neurochemical attributes (Ascoli et al., 2008;Chu and Anderson, 2015;Vitalis and Rossier, 2011;Wonders and Anderson, 2006). In the rodent neocortex, three non-overlapping subsets of interneurons have been defined based on the production of the calcium-binding proteins parvalbumin (PV) or calretinin (CR) or the peptide somatostatin (SST) (Gonchar and Burkhalter, 1997;Kubota et al., 1994;Xu et al., 2004). ...
Interneurons of the cerebral cortex play a significant role in cortical information processing and are of clinical interest due to their involvement in neurological disorders. In the human neocortex, three subsets of interneurons can be identified based on the production of the calcium-binding proteins parvalbumin, calretinin or calbindin. A subset of interneurons in the mouse cortex expresses the serotonin 3A receptor (5-HT3AR). Previous work in humans has also demonstrated the presence of a subgroup of cortical neurons that produces the catecholaminergic enzyme tyrosine hydroxylase (TH). Many TH-producing cells in the rat cortex coexpress calretinin and are adjacent to blood vessels. However, little is known about the phenotype of these TH interneurons in humans. Here we immunohistochemically examined the coexpression of TH with parvalbumin, calretinin, calbindin or 5-HT3AR in human Brodmann's areas 10 and 24, cortical regions with high densities of TH-containing neurons. Colocalization of TH with these calcium-binding proteins and with 5-HT3AR was not detected in either area. Cortical TH cells were rarely apposed to blood vessels, denoted by immunolabeling for the gliovascular marker aquaporin-4. Our results suggest that the TH-immunoreactive cells in the human cortex do not overlap with any known neurochemically-defined subsets of interneurons and provide further evidence of differences in the phenotype of these cells across species.
... The majority of these earlyborn MGE-derived INs express either parvalbumin (PV; PVALB -Mouse Genome Informatics) or somatostatin (SST) and migrate dorsally to populate deep layers of the neocortex (Valcanis and Tan, 2003;Wichterle et al., 2001;Xu et al., 2004). The caudal ganglionic eminence (CGE) is responsible for producing lateborn INs (∼30% of all INs) (Miyoshi et al., 2010;Nery et al., 2002;Rudy et al., 2011;Vitalis and Rossier, 2011), which preferentially integrate superficial layers of the neocortex, whereas the POA contributes to a minor pool of cortical INs (Gelman et al., 2009(Gelman et al., , 2011. The serotonergic ionotropic receptor 5HT3aR (HTR3A -Mouse Genome Informatics) is expressed in the neocortex in all CGE-derived GABAergic INs, such as bipolar calretinin (CR; CALB2 -Mouse Genome Informatics)-, vasoactive intestinal peptide (VIP)-, cholecystokinin (CCK)and reelin (RLN; RELN -Mouse Genome Informatics)expressing cells, including multipolar or neurogliaform INs expressing neuropeptide Y (NPY), but not in PV-and SSTpositive INs (Murthy et al., 2014;Lee et al., 2010;Vucurovic et al., 2010). ...
GABAergic interneurons are highly heterogenous and originate in the subpallium mainly from the medial (MGE) and caudal (CGE) ganglionic eminences according to a precise temporal sequence. While MGE-derived cells disperse dorsally and migrate towards all regions of the cortex, little is known on how CGE-derived cells reach their targets during development. Here, we unravel the existence of two novel CGE caudo-rostral migratory streams, one located laterally (LMS) and the other one more medially (MMS) that, together with the well-known caudal migratory stream (CMS), contribute to populate the neocortex, hippocampus and amygdala. These paths appear in a precise temporal sequence and express a distinct combination of transcription factors, such as Sp8, Prox1, COUP-TFI and COUP-TFII. By inactivating COUP-TFI in developing interneurons, the lateral and medial streams are perturbed and expression of Sp8 and COUP-TFII affected. As a consequence, adult mutant neocortices have laminar-specific alterations of distinct cortical interneuron subtypes. Overall, we propose that the existence of spatially and temporally regulated migratory paths in the subpallium contributes to the laminar distribution and specification of distinct interneuron subpopulations in the adult brain.
