Development and Functional Diversification of Cortical Interneurons

In the paper

“cortical γ-aminobutyric acid-containing (GABAergic) neurons are born in the same embryonic region of the telencephalon that generates the basal ganglia, the subpallium, from where they migrate tangentially to reach their final destination”

• Also stated in: § Emergence of cortical interneuron diversity · plain

  “The embryonic subpallium generates all GABAergic neurons in the telencephalon.”

What the sources say

• Not checked yetcites Anderson et al., 1997a

In the paper

“Current estimates suggest that up to 50 different types of GABAergic neurons may populate the cerebral cortex”

• Also stated in: § A simplified account of the interneuron universe · hedged

  “Currently available transcriptomic data suggests that up to 50 distinct transcriptional signatures (final number may vary as sequencing depth and analytical methods improve) can be distinguished among inhibitory neurons in the cerebral cortex”

What the sources say

• Not checked yetcites Harris et al., 2018 source
• Not checked yetcites Tasic et al., 2016 source
• Not checked yetcites Tasic et al., 2017

In the paper

“Two additional types of interneuron express 5HT3aR: NPY+ multipolar cells and Meis2+ interstitial GABAergic neurons. NPY+ multipolar interneurons exhibit irregular spiking properties and are particularly abundant at the boundary between layers 1 and 2”

• Also stated in: § A simplified account of the interneuron universe · plain

  “Meis2+ neurons reside in the white matter and extend axons to deep layers of the cortex and striatum”

What the sources say

• Not checked yetcites Gelman et al., 2009 source
• Not checked yetcites Miyoshi et al., 2010 source
• Not checked yetcites Frazer et al., 2017 source

In the paper

“SST+ Martinotti cells constitute a transcriptionally heterogeneous group of interneurons characterized by an ascending axon that arborizes profusely in layer 1”

What the sources say

• Not checked yetcites Hilscher et al., 2017 source
• Not checked yetcites Wang et al., 2004 source
• Not checked yetcites Xu et al., 2006

In the paper

“Multipolar VIP+ cells are transcriptionally very different from bipolar interneurons. Indeed, they are basket cells that co-express the neuropeptide cholecystokinin (CCK) and so they are transcriptionally more similar to other CCK+ basket cells that lack the expression of VIP”

What the sources say

• Not checked yetcites He et al., 2016
• Not checked yetcites Tasic et al., 2017

In the paper

“CCK+ basket cells that co-express VIP have a small soma and are particularly abundant in supragranular layers of the cortex, whereas CCK+ basket cells lacking VIP are enriched in layers 5 and 6”

What the sources say

• Not checked yetcites He et al., 2016

In the paper

“PV+ basket cells are the most abundant type of interneuron in the neocortex. They have highly torturous axons that form synapses on the soma and proximal dendrites of pyramidal cells and other interneurons”

What the sources say

• Not checked yetcites Hu et al., 2014

In the paper

“interneurons expressing vasoactive intestinal peptide (VIP) are one of the largest subclasses. They are mainly disinhibitory because they preferentially target SST+ and PV+ interneurons”

What the sources say

• Not checked yetcites Jiang et al., 2015 source

In the paper

“Both types of CCK+ interneurons express 5HT3aR”

• Also stated in: § A simplified account of the interneuron universe · plain

  “CCK+ basket cells make synapses on the soma of pyramidal cells and other interneurons and exhibit regular or burst spiking firing”

What the sources say

• Not checked yetcites Rudy et al., 2011 source
• Not checked yetcites Kawaguchi and Kubota, 1998

In the paper

“They are distributed through layers 2 to 6 in the neocortex and across all cortical regions.”

In the paper

“SST+ non-Martinotti cells are found throughout layers 2 to 6 and characteristically lack axons in layer 1. They exhibit lower resting membrane potential and higher firing frequency than Martinotti cells but lower than PV+ basket cells”

What the sources say

• Not checked yetcites Nigro et al., 2018 source
• Not checked yetcites Xu et al., 2006

In the paper

“the neocortex contains a population of long-range GABAergic projection neuron that express SST. These cells are most abundant in deep layers and project to other regions of the neocortex.”

• Also stated in: § A simplified account of the interneuron universe · plain

  “They have adapting and irregular spiking firing properties, frequently co-express nitric oxide synthase (NOS), chondrolectin (Chodl) and neuropeptide Y (NPY)”

What the sources say

• Not checked yetcites He et al., 2016
• Not checked yetcites Dittrich et al., 2012 source

In the paper

“The most characteristic VIP+ interneurons are bipolar cells with vertically oriented axons. They are highly enriched in layers 2 and 3, and often display continuous adapting firing properties”

What the sources say

• Not checked yetcites Pronneke et al., 2015 source

In the paper

“Martinotti cells are particularly abundant in layer 5, but they are also common in layers 2 and 3. These cells represent approximately 60% of the SST+ neurons in these layers”

What the sources say

• Not checked yetcites Jiang et al., 2015 source
• Not checked yetcites Nigro et al., 2018 source

In the paper

“Transcriptional analysis of individual cells from different regions of the brain suggests that neuronal diversity is organized hierarchically, which has led to the suggestion that the relationships that exist among different neuronal types can be considered, in practical terms, analogous to those of species”

What the sources say

• Not checked yetcites Zeng and Sanes, 2017 source

In the paper

“Single bouquet cells are also abundant in layer 1 and are transcriptionally similar to neurogliaform cells”

• Also stated in: § A simplified account of the interneuron universe · plain

  “but in contrast to these they have axonal ramifications that extend to deep layers of the cortex”

What the sources say

• Not checked yetcites Tasic et al., 2017
• Not checked yetcites Jiang et al., 2015 source

In the paper

“PV+ translaminar interneurons constitute a relatively rare type of fast-spiking interneurons that is particularly abundant in layers 5 and 6”

• Also stated in: § A simplified account of the interneuron universe · plain

  “these interneurons target pyramidal cells across several layers”

What the sources say

• Not checked yetcites Bortone et al., 2014 source
• Not checked yetcites Buchanan et al., 2012 source

In the paper

“the different types of interneurons establish stereotyped connections and express specific combinations of channels that endow them with unique electrophysiological properties”

What the sources say

• Not checked yetcites Ascoli et al., 2008 source

In the paper

“Martinotti cells have relatively heterogenous firing patterns but they often mediate disynaptic inhibition”

What the sources say

• Not checked yetcites Silberberg and Markram, 2007 source

In the paper

“most of which probably represent equivalent cell types”

In the paper

“The largest class of cortical interneuron is characterized by the expression of PV.”

In the paper

“Neurogliaform cells are the most abundant type of interneuron in layer 1, although they are also sparsely distributed through other layers. They have a very dense and characteristic axonal arbor and late spiking firing properties.”

• Also stated in: § A simplified account of the interneuron universe · plain

  “Neurogliaform cells express 5HT3aR and very often co-express reelin and NPY”

What the sources say

• Not checked yetcites Lee et al., 2010 source

In the paper

“Three major subclasses of PV+ interneurons can be distinguished, all of which exhibit characteristic fast-spiking firing properties: chandelier cells, basket cells and translaminar interneurons.”

In the paper

“They are particularly abundant at the border between layers 1 and 2 and in layer 6”

• Also stated in: § A simplified account of the interneuron universe · plain

  “their regional distribution is very heterogeneous”

What the sources say

• Not checked yetcites Taniguchi et al., 2013 source
• Not checked yetcites Inda et al., 2009 source

In the paper

“Cortical interneurons can be organized into several major classes based on their transcriptional similarities and the expression of selective markers”

In the paper

“Non-Martinotti cells are particularly abundant in layer 4”

• Also stated in: § A simplified account of the interneuron universe · plain

  “where they primarily target PV+ basket cells”

What the sources say

• Not checked yetcites Ma et al., 2006
• Not checked yetcites Xu et al., 2013

In the paper

“The POH, the most caudal progenitor domain in the preoptic region, lacks expression of Nkx2-1 and exhibit molecular similarities with the CGE”

What the sources say

• Not checked yetcites Flames et al., 2007 source

In the paper

“The LGE and CGE share many molecular markers, but the specific expression of transcription factors such as Nr2f2 bestow CGE progenitors with the ability to generate interneurons that migrate to the cerebral cortex”

What the sources say

• Not checked yetcites Kanatani et al., 2008 source
• Not checked yetcites Tripodi et al., 2004 source

In the paper

“Nkx6-2+ progenitor cells produce several types of SST+ neurons along with some PV+ basket cells and chandelier cells, and a mixed progeny of interneurons from the SST+ and PV+ classes has also been described for Etv1+ progenitor cells”

What the sources say

• Not checked yetcites He et al., 2016

In the paper

“SST+ interneurons are more abundant in infragranular than in supragranular layers of the neocortex, while PV+ basket cells – which constitute the majority of PV+ interneurons – are found throughout all layers with the exception of layer 1.”

In the paper

“the MGE can be further subdivided into dorsal, intermediate and ventrocaudal domains”

• Also stated in: § Spatial specification of interneuron progenitor cells · hedged

  “although progenitor pools in the subpallium do not seem to segregate as sharply as in the spinal cord”

What the sources say

• Not checked yetcites Jessell, 2000 source

In the paper

“These observations suggest that most (perhaps all) progenitor cells in the VZ of the MGE have the potential to generate distinct types of interneuron – within the limits imposed by the molecular specification of this region –, implying a temporal control of interneuron cell fate that is still poorly understood”

In the paper

“Thus, the preoptic region consists of two adjacent progenitor domains – POA and POH – that exhibit molecular similarities with the MGE and CGE, respectively.”

In the paper

“chandelier cells are most frequent in layers 2 and 6 of neocortex although they are preferentially generated toward the end of neurogenesis”

What the sources say

• Not checked yetcites Inan et al., 2012 source
• Not checked yetcites Taniguchi et al., 2013 source

In the paper

“Neurogliaform cells and multipolar NPY+ interneurons are born in the preoptic region”

What the sources say

• Not checked yetcites Gelman et al., 2009 source
• Not checked yetcites Niquille et al., 2018 source

In the paper

“the dorsal MGE has a strong bias toward the generation of SST+ interneurons, whereas the ventrocaudal domains produce a larger fraction of PV+ neurons”

What the sources say

• Not checked yetcites Flames et al., 2007 source
• Not checked yetcites Fogarty et al., 2007 source
• Not checked yetcites He et al., 2016

In the paper

“MGE progenitors generate most SST+ interneurons during the first half of the neurogenic period, whereas PV+ interneurons are produced at an almost constant rate throughout neurogenesis”

What the sources say

• Not checked yetcites Inan et al., 2012 source
• Not checked yetcites Miyoshi et al., 2007 source

In the paper

“The dorsal MGE is enriched in progenitor cells that express the homeodomain transcription factor Nkx6-2, whereas progenitor cells expressing the ETS transcription factor Etv1 are most abundant in the intermediate and ventrocaudal domains.”

In the paper

“The intermediate MGE produces both PV+ and SST+ interneurons with a rostral (PV+) to caudal (SST+) bias”

What the sources say

• Not checked yetcites Hu et al., 2017a
• Not checked yetcites Inan et al., 2012 source

In the paper

“The regional identity of the MGE and POA is specified by the homeobox transcription factor Nkx2-1, which is induced in the ventral subpallium prior to the onset of neurogenesis in this region. Expression of Nkx2-1 confers progenitor cells in the MGE and POA with unique properties that distinguish them from the adjacent LGE, CGE and POH regions.”

In the paper

“the generation of cortical interneurons is largely limited to the dorsal and intermediate domains of the MGE, whereas the ventrocaudal domain specializes in the production of PV+ projection neurons for the globus pallidus”

What the sources say

• Not checked yetcites Flandin et al., 2010 source
• Not checked yetcites Nóbrega-Pereira et al., 2010 source

In the paper

“Most of these cells do not derive from Nkx2-1-expressing progenitor cells”

• Also stated in: § Spatial specification of interneuron progenitor cells · hedged

  “and so their most likely origin is the POH domain within the preoptic region”

What the sources say

• Not checked yetcites Niquille et al., 2018 source
• Not checked yetcites Torigoe et al., 2016 source

In the paper

“the generation of interneuron diversity in the embryonic subpallium seems to involve two patterning mechanisms: the spatial patterning of progenitor identities, which distinguishes VZ progenitor cells in the MGE, CGE, POA and POH, and the temporal patterning of progenitor lineages – at least in the MGE and CGE – to further expand neural diversity.”

In the paper

“experimentally reducing the number of SST+ neurons migrating through their normal route does not affect the ratio between Martinotti and non-Martinotti cells in the mature cortex (although it affects specific features of these cells)”

What the sources say

• Not checked yetcites Lim et al., 2018 source

In the paper

“Interestingly, the expression of these receptors (Nrp1 and Nrp2) is repressed by Nkx2-1, and so the expression (Nkx2-1ON) or downregulation (Nkx2-1OFF) of this transcription factor in postmitotic interneurons born in the MGE determine whether they are targeted to the striatum or the cerebral cortex, respectively (Nóbrega-Pereira et al., 2008).”

What the sources say

• Not checked yetcites Nóbrega-Pereira et al., 2008 source

In the paper

“which suggests that the specification of at least these two types of SST+ interneuron is independent of – and prior to – the selection of a migratory route”

What the sources say

• Not checked yetcites Lim et al., 2018 source

In the paper

“VZ progenitor cells in the dorsal MGE are already generating supragranular interneurons at E13.5, while at the same stage lineages in the intermediate MGE are producing infragranular layer interneurons”

What the sources say

• Not checked yetcites He et al., 2016

In the paper

“Interneurons disperse throughout the developing cortex via two large migratory streams, a superficial route that courses through the marginal zone (MZ), and a deep route that largely overlaps with the pallial subventricular zone (SVZ) (Lavdas et al., 1999; Wichterle et al., 2001). A smaller fraction of interneurons migrates through the subplate.”

What the sources say

• Not checked yetcites Lavdas et al., 1999 source
• Not checked yetcites Wichterle et al., 2001 source

In the paper

“Loss of Nr2f1 and Nr2f2 in the MGE leads to an abnormal increase in the number of PV+ projection neurons and interneurons at the expense of SST+ neurons, which suggests that these transcription factors normally promote SST+ interneuron cell fates within the temporal sequence of these lineages”

What the sources say

• Not checked yetcites Hu et al., 2017a

In the paper

“In sum, cell type-specific genetic programs seem to be established by the time interneurons become postmitotic, or at least by the time they reach the developing cortex.”

In the paper

“This suggests that cortical interneurons are already fated to become Martinotti or non-Martinotti cells in the embryonic subpallium prior to entering the cortex, and that the choice of a particular migratory route is part of the intrinsic program controlling the development of interneurons.”

What the sources say

• Not checked yetcites Lim et al., 2018 source

In the paper

“Work in the LGE indicates that direct neurogenesis might be particularly important at early stages of neurogenesis”

• Also stated in: § An integrated model of interneuron generation · plain

  “but it is relatively rare after E12.5, when rapid proliferative divisions expanding the pool of intermediate progenitor cells are most characteristic”

What the sources say

• Not checked yetcites Anderson et al., 1997b
• Not checked yetcites Kelly et al., 2018 source
• Not checked yetcites Sheth and Bhide, 1997

In the paper

“previous work suggesting that SST+ interneurons are preferentially generated from VZ progenitors through direct neurogenesis”

What the sources say

• Not checked yetcites Petros et al., 2015 source

In the paper

“the proposed model implies that neuronal specification occurs primarily at the level of intermediate progenitor cells for all neurons generated in the MGE and CGE”

In the paper

“Although the expression of ErbB4 is confined to specific types of interneuron in the adult cortex (Fazzari et al., 2010; Neddens and Buonanno, 2010; Vullhorst et al., 2009), ErbB4 is expressed in the majority of cortical interneurons at perinatal stages (Bean et al., 2014).”

What the sources say

• Not checked yetcites Fazzari et al., 2010 source
• Not checked yetcites Bean et al., 2014 source

In the paper

“Interneurons from the MGE, CGE and preoptic region use essentially the same cellular mechanisms to translocate to the cortex (Marín et al., 2006; Martini et al., 2009; Yanagida et al., 2012), and it is therefore perhaps not surprising that they exhibit great transcriptional similarity at this stage (Mayer et al., 2018).”

What the sources say

• Not checked yetcites Marín et al., 2006 source
• Not checked yetcites Martini et al., 2009 source
• Not checked yetcites Yanagida et al., 2012 source

In the paper

“the integration of these cells in specific layers of the neocortex would expose them to different influences, which would shape their final features, through activity-dependent mechanisms”

What the sources say

• Not checked yetcites Wamsley and Fishell, 2017

In the paper

“This would suggest that lineages might get exhausted after generating a certain number of cortical interneurons, whose laminar distribution would depend on their time of neurogenesis.”

In the paper

“Interneurons undergo a protracted period of migration before they reach their final position within the cortex”

• Also stated in: § Timing of interneuron cell specification · plain

  “it is only at this point that the different types of cortical interneuron become distinguishable from each other”

What the sources say

• Not checked yetcites Bartolini et al., 2013 source
• Not checked yetcites Marín and Rubenstein, 2001

In the paper

“Nr2f1 and Nr2f2 influence neuronal specification by regulating cell cycle dynamics”

• Also stated in: § An integrated model of interneuron generation · hedged

  “which may explain why factors involved in the regulation of the cell cycle have also been involved in the regulation of interneuron diversity”

What the sources say

• Not checked yetcites Naka et al., 2008 source
• Not checked yetcites Glickstein et al., 2007 source
• Not checked yetcites Petros et al., 2015 source

In the paper

“The function of Nrg1 is mediated by the tyrosine kinase receptor ErbB4, the main neuregulin receptor expressed by interneurons (Flames et al., 2004; Yau et al., 2003).”

What the sources say

• Not checked yetcites Flames et al., 2004 source
• Not checked yetcites Yau et al., 2003 source

In the paper

“In addition, recent work suggests that pyramidal cells in the cortical plate express a different member of the neuregulin family, Nrg3, and this molecule facilitates the dispersion of cortical interneurons in the laminar dimension of the cortex (Bartolini et al., 2017).”

What the sources say

• Not checked yetcites Bartolini et al., 2017 source

In the paper

“Recent work has added further support to this idea by showing that SST+ Martinotti and PV+ translaminar interneurons migrate preferentially through the MZ, while non-Martinotti cells disperse via the SVZ (Lim et al., 2018).”

What the sources say

• Not checked yetcites Lim et al., 2018 source

In the paper

“This indicates that the development of layer 1 axons by SST+ Martinotti cells is facilitated by their interactions with components of the MZ at early neonatal stages, which demonstrates that the cortical microenvironment is crucial for the acquisition of specific features in specific types of interneuron.”

In the paper

“The termination of cortical interneuron migration is linked to the upregulation of the potassium/chloride exchanger KCC2 in interneurons, which halts the motility of interneurons by reducing the frequency of spontaneous intracellular calcium transients in response to GABA (Bortone and Polleux, 2009).”

What the sources say

• Not checked yetcites Bortone and Polleux, 2009

In the paper

“The fact that not all interneurons migrating through the MZ acquire the morphology of SST+ Martinotti cells reinforces the idea that these features are intrinsically-encoded, although they require the correct local environment – in this case, the MZ – to unfold appropriately.”

In the paper

“These studies seem to contradict earlier work, which concluded that clonally-related interneurons have a strong tendency to cluster in the mouse neocortex (Brown et al., 2011; Ciceri et al., 2013).”

What the sources say

• Not checked yetcites Brown et al., 2011 source
• Not checked yetcites Ciceri et al., 2013 source

In the paper

“Layer 4 receives the vast majority of thalamocortical input, and so it plays a prominent role in the initial processing of sensory information (Douglas and Martin, 2004).”

What the sources say

• Not checked yetcites Douglas and Martin, 2004 source

In the paper

“Interestingly, layer 5 SST+ interneurons receive dense transient thalamic inputs during the first week of postnatal development and innervate both layer 4 excitatory neurons and layer 5 pyramidal cells and immature PV+ interneurons (Marques-Smith et al., 2016; Tuncdemir et al., 2016).”

What the sources say

• Not checked yetcites Marques-Smith et al., 2016 source
• Not checked yetcites Tuncdemir et al., 2016 source

In the paper

“However, the connectivity between these interneurons and excitatory neurons in layer 4 remains relatively weak until the second postnatal week, when PV+ basket cells begin receiving direct inputs from thalamic neurons (Chittajallu and Isaac, 2010; Daw et al., 2007).”

What the sources say

• Not checked yetcites Chittajallu and Isaac, 2010
• Not checked yetcites Daw et al., 2007 source

In the paper

“These findings suggest that at least some components of the transcriptional module controlling the migration of cortical interneurons are not universal, although they might be shared by certain types (e.g., SST+ Martinotti cells and PV+ translaminar interneurons).”

In the paper

“Feedforward inhibition is critical in this process, as it sharpens receptive fields and regulates temporal integration and timing (Gabernet et al., 2005; Wehr and Zador, 2003).”

What the sources say

• Not checked yetcites Gabernet et al., 2005 source
• Not checked yetcites Wehr and Zador, 2003

In the paper

“These observations indicate that interneurons require excitatory inputs to mature normally during the first week of postnatal development, and that their ability to integrate into functional circuits influence their probability of survival.”

In the paper

“Columnar refinement begins at the end of the first postnatal week and requires thalamocortical inputs.”

What the sources say

• Not checked yetcites Shepherd et al., 2003 source

In the paper

“Consistent with this idea, increasing or decreasing the excitability of pyramidal cells using DREADDs during the period of interneuron programmed cell death respectively enhances or diminishes the survival of cortical interneurons (Wong et al., 2018).”

What the sources say

• Not checked yetcites Wong et al., 2018 source

In the paper

“Inhibition is likely more prominent on weakly activated layer 2/3 pyramidal cells immediately above septal regions than in layer 2/3 pyramidal cells above the barrels (where VPM axons concentrate), which would contribute to the formation of barrel columns tuned to individual whiskers (Che et al., 2018).”

What the sources say

• Not checked yetcites Che et al., 2018 source

In the paper

“While experience-dependent plasticity at excitatory synapses is known to contribute to the maturation of neuronal circuits in superficial layers of the cortex (Bender et al., 2006), recent work suggests that a specific population of interneurons is also involved in this process.”

What the sources say

• Not checked yetcites Bender et al., 2006 source

In the paper

“In sensory deprived mice, layer 2/3 neurons receive stronger inputs from layer 4 neurons in septal regions altered, which suggests that the normal maturation of the columnar organization requires competitive interactions among layer 4 neurons (Shepherd et al., 2003).”

What the sources say

• Not checked yetcites Shepherd et al., 2003 source

In the paper

“For example, PV+ basket cells seem to dynamically oscillate between different “states” in response to neuronal activity, a process that is required for learning and memory in the adult brain (Donato et al., 2013; Lagler et al., 2016).”

What the sources say

• Not checked yetcites Donato et al., 2013 source
• Not checked yetcites Lagler et al., 2016 source

In the paper

“GABA has been shown to influence neuronal migration in the embryonic cortex (Behar et al., 2000; López-Bendito et al., 2003), the settlement of interneurons in the cortical plate (Bortone and Polleux, 2009), and the formation on inhibitory synapses (Oh et al., 2016), and may also influence the neurogenesis of pyramidal cells (Silva et al., 2018).”

What the sources say

• Not checked yetcites Behar et al., 2000 source
• Not checked yetcites Bortone and Polleux, 2009
• Not checked yetcites Oh et al., 2016

In the paper

“The cellular organization of interneuron diversity is remarkably similar between mouse and human, but there are important differences in the morphology, gene expression, laminar distribution and proportions of certain types of interneurons (Boldog et al., 2018; DeFelipe, 1997; Hodge et al., 2018).”

What the sources say

• Not checked yetcites Boldog et al., 2018 source
• Not checked yetcites DeFelipe, 1997 source
• Not checked yetcites Hodge et al., 2018

In the paper

“In contrast, neuronal activity induces a completely different transcriptional response in VIP+ interneurons, promoting the formation of inhibitory synapses on these cells (Mardinly et al., 2016).”

What the sources say

• Not checked yetcites Mardinly et al., 2016 source

In the paper

“Inhibitory circuits share general organization principles across cortical areas, but increasing evidence suggests that the abundance of specific inhibitory connectivity motifs varies between regions (Katzel et al., 2011), probably reflecting different computational requirements.”

What the sources say

• Not checked yetcites Katzel et al., 2011 source

In the paper

“In supragranular PV+ basket cells, neuronal activity modulates the expression and subcellular location (cytoplasmic or nuclear) of the transcription factor Etv1 (Dehorter et al., 2015), which in turn induces the expression of Kv1.1.”

What the sources say

• Not checked yetcites Dehorter et al., 2015 source

In the paper

“However, since genomic variation associated to neuropsychiatric disorders such as autism and schizophrenia affects the developing brain, the relevant transcriptional information for this type of analyses would likely need to be developmental.”