Publications by authors named "Natalia De Marco Garcia"

19 Publications

  • Page 1 of 1

The Emergence of Network Activity Patterns in the Somatosensory Cortex - An Early Window to Autism Spectrum Disorders.

Neuroscience 2021 Apr 19. Epub 2021 Apr 19.

Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address:

Across mammalian species, patterned activity in neural populations is a prominent feature of developing sensory cortices. Numerous studies have long appreciated the diversity of these patterns, characterizing their differences in spatial and temporal dynamics. In the murine somatosensory cortex, neuronal co-activation is thought to guide the formation of sensory maps and prepare the cortex for sensory processing after birth. While pioneering studies deftly utilized slice electrophysiology and unit recordings to characterize correlated activity, a detailed understanding of the underlying circuits remains poorly understood. More recently, advances in in vivo calcium imaging in awake mouse pups and increasing genetic tractability of neuronal types have allowed unprecedented manipulation of circuit components at select developmental timepoints. These novel approaches have proven fundamental in uncovering the identity of neurons engaged in correlated activity during development. In particular, recent studies have highlighted interneurons as key in refining the spatial extent and temporal progression of patterned activity. Here, we discuss how emergent synchronous activity across the first postnatal weeks is shaped by underlying gamma aminobutyric acid (GABA)ergic contributors in the somatosensory cortex. Further, the importance of participation in specific activity patterns per se for neuronal maturation and perdurance will be of particular highlight in this survey of recent literature. Finally, we underscore how aberrant neuronal synchrony and disrupted inhibitory interneuron activity underlie sensory perturbations in neurodevelopmental disorders, particularly Autism Spectrum Disorders (ASDs), emphasizing the importance of future investigative approaches that incorporate the spatiotemporal features of patterned activity alongside the cellular components to probe disordered circuit assembly.
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http://dx.doi.org/10.1016/j.neuroscience.2021.04.005DOI Listing
April 2021

The Logic of Developing Neocortical Circuits in Health and Disease.

J Neurosci 2021 02 11;41(5):813-822. Epub 2021 Jan 11.

University of California San Diego, Kavli Institute for Brain and Mind, La Jolla, California 92093.

The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention.
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http://dx.doi.org/10.1523/JNEUROSCI.1655-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880298PMC
February 2021

The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.

Nat Commun 2020 01 16;11(1):319. Epub 2020 Jan 16.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
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http://dx.doi.org/10.1038/s41467-019-14082-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965647PMC
January 2020

GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex.

Neuron 2020 01 25;105(1):75-92.e5. Epub 2019 Nov 25.

Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address:

During neonatal development, sensory cortices generate spontaneous activity patterns shaped by both sensory experience and intrinsic influences. How these patterns contribute to the assembly of neuronal circuits is not clearly understood. Using longitudinal in vivo calcium imaging in un-anesthetized mouse pups, we show that spatially segregated functional assemblies composed of interneurons and pyramidal cells are prominent in the somatosensory cortex by postnatal day (P) 7. Both reduction of GABA release and synaptic inputs onto pyramidal cells erode the emergence of functional topography, leading to increased network synchrony. This aberrant pattern effectively blocks interneuron apoptosis, causing increased survival of parvalbumin and somatostatin interneurons. Furthermore, the effect of GABA on apoptosis is mediated by inputs from medial ganglionic eminence (MGE)-derived but not caudal ganglionic eminence (CGE)-derived interneurons. These findings indicate that immature MGE interneurons are fundamental for shaping GABA-driven activity patterns that balance the number of interneurons integrating into maturing cortical networks.
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http://dx.doi.org/10.1016/j.neuron.2019.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982374PMC
January 2020

Assemblies of Perisomatic GABAergic Neurons in the Developing Barrel Cortex.

Neuron 2020 01 25;105(1):93-105.e4. Epub 2019 Nov 25.

Aix Marseille Univ, INSERM, INMED, Turing Center for Living Systems, Marseille, France. Electronic address:

The developmental journey of cortical interneurons encounters several activity-dependent milestones. During the early postnatal period in developing mice, GABAergic neurons are transient preferential recipients of thalamic inputs and undergo activity-dependent migration arrest, wiring, and programmed cell-death. Despite their importance for the emergence of sensory experience and the role of activity in their integration into cortical networks, the collective dynamics of GABAergic neurons during that neonatal period remain unknown. Here, we study coordinated activity in GABAergic cells of the mouse barrel cortex using in vivo calcium imaging. We uncover a transient structure in GABAergic population dynamics that disappears in a sensory-dependent process. Its building blocks are anatomically clustered GABAergic assemblies mostly composed by prospective parvalbumin-expressing cells. These progressively widen their territories until forming a uniform perisomatic GABAergic network. Such transient patterning of GABAergic activity is a functional scaffold that links the cortex to the external world prior to active exploration. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.neuron.2019.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537946PMC
January 2020

Cocaine- and stress-primed reinstatement of drug-associated memories elicit differential behavioral and frontostriatal circuit activity patterns via recruitment of L-type Ca channels.

Mol Psychiatry 2020 10 9;25(10):2373-2391. Epub 2019 Sep 9.

Department of Pediatric Neurology, Pediatrics, Weill Cornell Medicine, New York, NY, 10065, USA.

Cocaine-associated memories are critical drivers of relapse in cocaine-dependent individuals that can be evoked by exposure to cocaine or stress. Whether these environmental stimuli recruit similar molecular and circuit-level mechanisms to promote relapse remains largely unknown. Here, using cocaine- and stress-primed reinstatement of cocaine conditioned place preference to model drug-associated memories, we find that cocaine drives reinstatement by increasing the duration that mice spend in the previously cocaine-paired context whereas stress increases the number of entries into this context. Importantly, both forms of reinstatement require Ca1.2 L-type Ca channels (LTCCs) in cells of the prelimbic cortex that project to the nucleus accumbens core (PrL→NAcC). Utilizing fiber photometry to measure circuit activity in vivo in conjunction with the LTCC blocker, isradipine, we find that LTCCs drive differential recruitment of the PrL→ NAcC pathway during cocaine- and stress-primed reinstatement. While cocaine selectively activates PrL→NAcC cells prior to entry into the cocaine-paired chamber, a measure that is predictive of duration in that chamber, stress increases persistent activity of this projection, which correlates with entries into the cocaine-paired chamber. Using projection-specific chemogenetic manipulations, we show that PrL→NAcC activity is required for both cocaine- and stress-primed reinstatement, and that activation of this projection in Ca1.2-deficient mice restores reinstatement. These data indicate that LTCCs are a common mediator of cocaine- and stress-primed reinstatement. However, they engage different patterns of behavior and PrL→NAcC projection activity depending on the environmental stimuli. These findings establish a framework to further study how different environmental experiences can drive relapse, and supports further exploration of isradipine, an FDA-approved LTCC blocker, as a potential therapeutic for the prevention of relapse in cocaine-dependent individuals.
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http://dx.doi.org/10.1038/s41380-019-0513-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927165PMC
October 2020

The Impact of Perineuronal Net Digestion Using Chondroitinase ABC on the Intrinsic Physiology of Cortical Neurons.

Neuroscience 2018 09 10;388:23-35. Epub 2018 Jul 10.

Psychology Ph.D. Program, The Graduate Center, City University of New York (CUNY), United States; Neuroscience Major, Queens College, CUNY, United States; Psychology Department, Queens College, CUNY, United States; Neuroscience-Biology PhD Subprogram, The Graduate Center, CUNY, United States. Electronic address:

Perineuronal nets (PNNs) are a form of aggregate Extracellular Matrix (ECM) in the brain. Recent evidence suggests that the postnatal deposition of PNNs may play an active role in regulating neuroplasticity and, potentially, neurological disorders. Observations of high levels of PNN expression around somas, proximal dendrites, and axon initial segments of a subtype of neurons have also led to proposals that PNNs may modulate the intrinsic properties of the neurons they ensheathe. While high levels of PNNs are postnatally expressed throughout the neocortex, it is still unclear how they impact the neuronal physiology of the many classes and subtypes of neurons that exist. In this study, we demonstrate that Chondroitinase ABC digestion of PNNs from acute cortical slices from juvenile mice (P28-35) resulted in neuron-specific impacts on intrinsic physiology. Fast spiking (FS) interneurons showed decreased input resistance, resting membrane potential (RMP), reduced action potential (AP) peaks and altered spontaneous synaptic inputs. Low-Threshold Spiking interneurons showed altered rebound depolarizations and decreased frequency of spontaneous synaptic inputs. Putative excitatory neurons; regular spiking, bursting, and doublet phenotypes did not demonstrate any alterations. Our data indicate that chABC-sensitive PNNs may specifically regulate the intrinsic and synaptic physiology of inhibitory interneurons.
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http://dx.doi.org/10.1016/j.neuroscience.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338339PMC
September 2018

Layer I Interneurons Sharpen Sensory Maps during Neonatal Development.

Neuron 2018 07 21;99(1):98-116.e7. Epub 2018 Jun 21.

Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 10021, USA. Electronic address:

The neonatal mammal faces an array of sensory stimuli when diverse neuronal types have yet to form sensory maps. How these inputs interact with intrinsic neuronal activity to facilitate circuit assembly is not well understood. By using longitudinal calcium imaging in unanesthetized mouse pups, we show that layer I (LI) interneurons, delineated by co-expression of the 5HT3a serotonin receptor (5HT3aR) and reelin (Re), display spontaneous calcium transients with the highest degree of synchrony among cell types present in the superficial barrel cortex at postnatal day 6 (P6). 5HT3aR Re interneurons are activated by whisker stimulation during this period, and sensory deprivation induces decorrelation of their activity. Moreover, attenuation of thalamic inputs through knockdown of NMDA receptors (NMDARs) in these interneurons results in expansion of whisker responses, aberrant barrel map formation, and deficits in whisker-dependent behavior. These results indicate that recruitment of specific interneuron types during development is critical for adult somatosensory function. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.neuron.2018.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152945PMC
July 2018

Neuronal activity controls the development of interneurons in the somatosensory cortex.

Front Biol (Beijing) 2016 Dec 29;11(6):459-470. Epub 2016 Nov 29.

Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.

Background: Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.

Objective: In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.

Methods: We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: "interneuron", "somatosensory", "development", "activity", "network patterns", "thalamocortical", "NMDA receptor", "plasticity". We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.

Results: We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.

Conclusions: Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.
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http://dx.doi.org/10.1007/s11515-016-1427-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267357PMC
December 2016

Sensory inputs control the integration of neurogliaform interneurons into cortical circuits.

Nat Neurosci 2015 Mar 9;18(3):393-401. Epub 2015 Feb 9.

1] NYU Neuroscience Institute, New York Langone Medical Center, New York, New York, USA. [2] Department of Neuroscience and Physiology, New York Langone Medical Center, New York, New York, USA. [3] Department of Neural Science, New York University, New York, New York, USA.

Neuronal microcircuits in the superficial layers of the mammalian cortex provide the substrate for associative cortical computation. Inhibitory interneurons constitute an essential component of the circuitry and are fundamental to the integration of local and long-range information. Here we report that, during early development, superficially positioned Reelin-expressing neurogliaform interneurons in the mouse somatosensory cortex receive afferent innervation from both cortical and thalamic excitatory sources. Attenuation of ascending sensory, but not intracortical, excitation leads to axo-dendritic morphological defects in these interneurons. Moreover, abrogation of the NMDA receptors through which the thalamic inputs signal results in a similar phenotype, as well as in the selective loss of thalamic and a concomitant increase in intracortical connectivity. These results suggest that thalamic inputs are critical in determining the balance between local and long-range connectivity and are fundamental to the proper integration of Reelin-expressing interneurons into nascent cortical circuits.
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http://dx.doi.org/10.1038/nn.3946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624196PMC
March 2015

Subtype-selective electroporation of cortical interneurons.

J Vis Exp 2014 Aug 18(90):e51518. Epub 2014 Aug 18.

NYU Neuroscience Institute, New York University School of Medicine.

The study of central nervous system (CNS) maturation relies on genetic targeting of neuronal populations. However, the task of restricting the expression of genes of interest to specific neuronal subtypes has proven remarkably challenging due to the relative scarcity of specific promoter elements. GABAergic interneurons constitute a neuronal population with extensive genetic and morphological diversity. Indeed, more than 11 different subtypes of GABAergic interneurons have been characterized in the mouse cortex. Here we present an adapted protocol for selective targeting of GABAergic populations. We achieved subtype selective targeting of GABAergic interneurons by using the enhancer element of the homeobox transcription factors Dlx5 and Dlx6, homologues of the Drosophila distal-less (Dll) gene, to drive the expression of specific genes through in utero electroporation.
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http://dx.doi.org/10.3791/51518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243608PMC
August 2014

Parsing out the embryonic origin of subplate cell-type diversity.

Proc Natl Acad Sci U S A 2014 Jun 28;111(23):8325-6. Epub 2014 May 28.

Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 10021

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http://dx.doi.org/10.1073/pnas.1406937111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060649PMC
June 2014

Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons.

J Neurosci 2012 Dec;32(49):17690-705

New York University Neuroscience Institute and the Departments of Physiology and Neuroscience, NYU Langone Medical Center, New York, New York 10016, USA.

Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity, and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons, Satb1 (special AT-rich binding protein) promotes terminal differentiation, connectivity, and survival in interneurons that express PV and SST. We find that conditional removal of Satb1 in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex in Satb1 mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss of Satb1 function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for medial ganglionic eminence-derived interneuron differentiation, connectivity, and survival.
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http://dx.doi.org/10.1523/JNEUROSCI.3583-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654406PMC
December 2012

Functional adaptation of cortical interneurons to attenuated activity is subtype-specific.

Front Neural Circuits 2012 24;6:66. Epub 2012 Sep 24.

Smilow Neuroscience, NYU Langone Medical Center, Neuroscience Institute New York City, NY, USA.

Functional neuronal homeostasis has been studied in a variety of model systems and contexts. Many studies have shown that there are a number of changes that can be activated within individual cells or networks in order to compensate for perturbations or changes in levels of activity. Dissociating the cell autonomous from the network-mediated events has been complicated due to the difficulty of sparsely targeting specific populations of neurons in vivo. Here, we make use of a recent in vivo approach we developed that allows for the sparse labeling and manipulation of activity within superficial caudal ganglionic eminence (CGE)-derived GABAergic interneurons. Expression of the inward rectifying potassium channel Kir2.1 cell-autonomously reduced neuronal activity and lead to specific developmental changes in their intrinsic electrophysiological properties and the synaptic input they received. In contrast to previous studies on homeostatic scaling of pyramidal cells, we did not detect any of the typically observed compensatory mechanisms in these interneurons. Rather, we instead saw a specific alteration of the kinetics of excitatory synaptic events within the reelin-expressing subpopulation of interneurons. These results provide the first in vivo observations for the capacity of interneurons to cell-autonomously regulate their excitability.
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http://dx.doi.org/10.3389/fncir.2012.00066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449283PMC
October 2012

Neuronal activity is required for the development of specific cortical interneuron subtypes.

Nature 2011 Apr 3;472(7343):351-5. Epub 2011 Apr 3.

Smilow Neuroscience Program, Departments of Cell Biology and Neural Science, New York University Langone Medical Center, New York, New York 10016, USA.

Electrical activity has been shown to regulate development in a variety of species and in various structures, including the retina, spinal cord and cortex. Within the mammalian cortex specifically, the development of dendrites and commissural axons in pyramidal cells is activity-dependent. However, little is known about the developmental role of activity in the other major cortical population of neurons, the GABA-producing interneurons. These neurons are morphologically and functionally heterogeneous and efforts over the past decade have focused on determining the mechanisms that contribute to this diversity. It was recently discovered that 30% of all cortical interneurons arise from a relatively novel source within the ventral telencephalon, the caudal ganglionic eminence (CGE). Owing to their late birth date, these interneurons populate the cortex only after the majority of other interneurons and pyramidal cells are already in place and have started to functionally integrate. Here we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but not vasoactive intestinal peptide (VIP)-positive) interneurons, activity is essential before postnatal day 3 for correct migration, and that after postnatal day 3, glutamate-mediated activity controls the development of their axons and dendrites. Furthermore, we show that the engulfment and cell motility 1 gene (Elmo1), a target of the transcription factor distal-less homeobox 1 (Dlx1), is selectively expressed in Re(+) and Cr(+) interneurons and is both necessary and sufficient for activity-dependent interneuron migration. Our findings reveal a selective requirement for activity in shaping the cortical integration of specific neuronal subtypes.
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http://dx.doi.org/10.1038/nature09865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641515PMC
April 2011

Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity.

Neuron 2008 Jan;57(2):217-31

Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA.

The fidelity with which spinal motor neurons innervate their limb target muscles helps to coordinate motor behavior, but the mechanisms that determine precise patterns of nerve-muscle connectivity remain obscure. We show that Nkx6 proteins, a set of Hox-regulated homeodomain transcription factors, are expressed by motor pools soon after motor neurons leave the cell cycle, before the formation of muscle nerve side branches in the limb. Using mouse genetics, we show that the status of Nkx6.1 expression in certain motor neuron pools regulates muscle nerve formation, and the pattern of innervation of individual muscles. Our findings provide genetic evidence that neurons within motor pools possess an early transcriptional identity that controls target muscle specificity.
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http://dx.doi.org/10.1016/j.neuron.2007.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276619PMC
January 2008

Distinct roles for secreted semaphorin signaling in spinal motor axon guidance.

Neuron 2005 Dec;48(6):949-64

Howard Hughes Medical Institute, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Neuropilins, secreted semaphorin coreceptors, are expressed in discrete populations of spinal motor neurons, suggesting they provide critical guidance information for the establishment of functional motor circuitry. We show here that motor axon growth and guidance are impaired in the absence of Sema3A-Npn-1 signaling. Motor axons enter the limb precociously, showing that Sema3A controls the timing of motor axon in-growth to the limb. Lateral motor column (LMC) motor axons within spinal nerves are defasciculated as they grow toward the limb and converge in the plexus region. Medial and lateral LMC motor axons show dorso-ventral guidance defects in the forelimb. In contrast, Sema3F-Npn-2 signaling guides the axons of a medial subset of LMC neurons to the ventral limb, but plays no major role in regulating their fasciculation. Thus, Sema3A-Npn-1 and Sema3F-Npn-2 signaling control distinct steps of motor axon growth and guidance during the formation of spinal motor connections.
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http://dx.doi.org/10.1016/j.neuron.2005.12.003DOI Listing
December 2005

Regulation of motor neuron pool sorting by differential expression of type II cadherins.

Cell 2002 Apr;109(2):205-16

Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, New York, NY 10032, USA.

During spinal cord development, motor neurons with common targets and afferent inputs cluster into discrete nuclei, termed motor pools. Motor pools can be delineated by transcription factor expression, but cell surface proteins that distinguish motor pools in a systematic manner have not been identified. We show that the developmentally regulated expression of type II cadherins defines specific motor pools. Expression of one type II cadherin, MN-cadherin, regulates the segregation of motor pools that are normally distinguished by expression of this protein. Type II cadherins are also expressed by proprioceptive sensory neurons, raising the possibility that cadherins regulate additional steps in the development of sensory-motor circuits.
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http://dx.doi.org/10.1016/s0092-8674(02)00695-5DOI Listing
April 2002