Publications by authors named "Floor J Stam"

11 Publications

  • Page 1 of 1

Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits.

Neuron 2016 Feb;89(3):521-35

NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA. Electronic address:

The precise connectivity of somatostatin and parvalbumin cortical interneurons is generated during development. An understanding of how these interneuron classes incorporate into cortical circuitry is incomplete but essential to elucidate the roles they play during maturation. Here, we report that somatostatin interneurons in infragranular layers receive dense but transient innervation from thalamocortical afferents during the first postnatal week. During this period, parvalbumin interneurons and pyramidal neurons within the same layers receive weaker thalamocortical inputs, yet are strongly innervated by somatostatin interneurons. Further, upon disruption of the early (but not late) somatostatin interneuron network, the synaptic maturation of thalamocortical inputs onto parvalbumin interneurons is perturbed. These results suggest that infragranular somatostatin interneurons exhibit a transient early synaptic connectivity that is essential for the establishment of thalamic feedforward inhibition mediated by parvalbumin interneurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2015.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861073PMC
February 2016

Identification of a spinal circuit for light touch and fine motor control.

Cell 2015 Jan;160(3):503-15

Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:

Sensory circuits in the dorsal spinal cord integrate and transmit multiple cutaneous sensory modalities including the sense of light touch. Here, we identify a population of excitatory interneurons (INs) in the dorsal horn that are important for transmitting innocuous light touch sensation. These neurons express the ROR alpha (RORα) nuclear orphan receptor and are selectively innervated by cutaneous low threshold mechanoreceptors (LTMs). Targeted removal of RORα INs in the dorsal spinal cord leads to a marked reduction in behavioral responsiveness to light touch without affecting responses to noxious and itch stimuli. RORα IN-deficient mice also display a selective deficit in corrective foot movements. This phenotype, together with our demonstration that the RORα INs are innervated by corticospinal and vestibulospinal projection neurons, argues that the RORα INs direct corrective reflex movements by integrating touch information with descending motor commands from the cortex and cerebellum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2015.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431637PMC
January 2015

Identification of multiple subsets of ventral interneurons and differential distribution along the rostrocaudal axis of the developing spinal cord.

PLoS One 2013 15;8(8):e70325. Epub 2013 Aug 15.

Université catholique de Louvain, Institute of Neuroscience, Laboratory of Neural Differentiation, Brussels, Belgium.

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070325PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744532PMC
September 2014

Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus.

Proc Natl Acad Sci U S A 2013 May 13;110(22):9106-11. Epub 2013 May 13.

Laboratory of Genetics, The Salk Institute for Biological Sciences, La Jolla, CA 92037, USA.

New neurons, which have been implicated in pattern separation, are continually generated in the dentate gyrus in the adult hippocampus. Using a genetically modified rabies virus, we demonstrated that molecular layer perforant pathway (MOPP) cells innervated newborn granule neurons in adult mouse brain. Stimulating the perforant pathway resulted in the activation of MOPP cells before the activation of dentate granule neurons. Moreover, activation of MOPP cells by focal uncaging of glutamate induced strong inhibition of granule cells. Together, these results indicate that MOPP cells located in the molecular layer of the dentate gyrus contribute to feed-forward inhibition of granule cells via perforant pathway activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1306912110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670356PMC
May 2013

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program.

Development 2012 Jan 24;139(1):179-90. Epub 2011 Nov 24.

Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA.

The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.071134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231776PMC
January 2012

From circuits to behaviour: motor networks in vertebrates.

Curr Opin Neurobiol 2010 Feb 6;20(1):116-25. Epub 2010 Feb 6.

Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA.

Neural networks in the hindbrain and spinal cord generate the simple patterns of motor activity that are necessary for breathing and locomotion. These networks function autonomously, producing simple yet flexible rhythmic motor behaviours that are highly responsive to sensory inputs and central control. This review outlines recent advances in our understanding of the genetic programmes controlling the assembly and functioning of circuits in the hindbrain and spinal cord that are responsible for respiration and locomotion. In addition, we highlight the influence that target-derived retrograde signaling and experience-dependent mechanisms have on establishing connectivity, particularly with respect to sensory afferent innervation of the spinal cord.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.conb.2010.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847443PMC
February 2010

NFIL3 and cAMP response element-binding protein form a transcriptional feedforward loop that controls neuronal regeneration-associated gene expression.

J Neurosci 2009 Dec;29(49):15542-50

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.

Successful regeneration of damaged neurons depends on the coordinated expression of neuron-intrinsic genes. At present however, there is no comprehensive view of the transcriptional regulatory mechanisms underlying neuronal regeneration. We used high-content cellular screening to investigate the functional contribution of 62 transcription factors to regenerative neuron outgrowth. Ten transcription factors are identified that either increase or decrease neurite outgrowth. One of these, NFIL3, is specifically upregulated during successful regeneration in vivo. Paradoxically however, knockdown of NFIL3 and overexpression of dominant-negative NFIL3 both increase neurite outgrowth. Our data show that NFIL3, together with CREB, forms an incoherent feedforward transcriptional regulatory loop in which NFIL3 acts as a negative regulator of CREB-induced regeneration-associated genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.3938-09.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666114PMC
December 2009

Identification of candidate transcriptional modulators involved in successful regeneration after nerve injury.

Eur J Neurosci 2007 Jun;25(12):3629-37

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics & Cognitive Research, Faculty of Earth and Life Sciences, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.

Successful regeneration of injured neurons requires a complex molecular response that involves the expression, modification and transport of a large number of proteins. The identity of neuronal proteins responsible for the initiation of regenerative neurite outgrowth is largely unknown. Dorsal root ganglion (DRG) neurons display robust and successful regeneration following lesion of their peripheral neurite, whereas outgrowth of central neurites is weak and does not lead to functional recovery. We have utilized this differential response to gain insight in the early transcriptional events associated with successful regeneration. Surprisingly, our study shows that peripheral and central nerve crushes elicit very distinct transcriptional activation, revealing a large set of novel genes that are differentially regulated within the first 24 h after the lesion. Here we show that Ankrd1, a gene known to act as a transcriptional modulator, is involved in neurite outgrowth of a DRG neuron-derived cell line as well as in cultured adult DRG neurons. This gene, and others identified in this study, may be part of the transcriptional regulatory module that orchestrates the onset of successful regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1460-9568.2007.05597.xDOI Listing
June 2007

The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease.

Mol Cell Neurosci 2006 May-Jun;32(1-2):102-17. Epub 2006 May 3.

Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, Netherlands.

Neuromuscular synapses differ markedly in their plasticity. Motor nerve terminals innervating slow muscle fibers sprout vigorously following synaptic blockage, while those innervating fast-fatigable muscle fibers fail to exhibit any sprouting. Here, we show that the axon repellent Semaphorin 3A is differentially expressed in terminal Schwann cells (TSCs) on different populations of muscle fibers: postnatal, regenerative and paralysis induced remodeling of neuromuscular connections is accompanied by increased expression of Sema3A selectively in TSCs on fast-fatigable muscle fibers. To our knowledge, this is the first demonstration of a molecular difference between TSCs on neuromuscular junctions of different subtypes of muscle fibers. Interestingly, also in a mouse model for amyotrophic lateral sclerosis (ALS), Sema3A is expressed at NMJs of fast-fatigable muscle fibers. We propose that expression of Sema3A by TSCs not only suppresses nerve terminal plasticity at specific neuromuscular synapses, but may also contribute to their early and selective loss in the motor neuron disease ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mcn.2006.03.002DOI Listing
September 2006

Proteomics of the injured rat sciatic nerve reveals protein expression dynamics during regeneration.

Mol Cell Proteomics 2005 Feb 25;4(2):120-32. Epub 2004 Oct 25.

Department of Molecular and Cellular Neurobiology, Research Institute Neurosciences Amsterdam, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.

Using proteomics, we investigated the temporal expression profiles of proteins in rat sciatic nerve after experimental crush. Extracts of sciatic nerves collected at 5, 10, and 35 days after injury were analyzed by two-dimensional gel electrophoresis and quantitative image analysis. Of the approximately 1,500 protein spots resolved on each gel, 121 showed significant regulation during at least one time point. Using cluster analysis, these proteins were grouped into two expression profiles of down-regulation and four of up-regulation. These profiles mainly reflected differences in cellular origins in addition to different functional roles. Mass spectrometric analysis identified 82 proteins pertaining to several functional classes, i.e. acute-phase proteins, antioxidant proteins, and proteins involved in protein synthesis/maturation/degradation, cytoskeletal (re)organization, and in lipid metabolism. Several proteins not previously implicated in nerve regeneration were identified, e.g. translationally controlled tumor protein, annexin A9/31, vitamin D-binding protein, alpha-crystallin B, alpha-synuclein, dimethylargininases, and reticulocalbin. Real-time PCR analysis of selected genes showed which were expressed in the nerve versus the dorsal root ganglion neurons. In conclusion, this study highlights the complexity and temporal aspect of the molecular process underlying nerve regeneration and points to the importance of glial and inflammatory determinants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/mcp.M400076-MCP200DOI Listing
February 2005

Very low levels of the glucocorticoid receptor beta isoform in the human hippocampus as shown by Taqman RT-PCR and immunocytochemistry.

Brain Res Mol Brain Res 2003 Aug;116(1-2):17-26

Division of Medical Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands.

The hippocampus is an important target for glucocorticoid hormones. Glucocorticoid receptor (GR) mediated feedback in this area is important for control of behavioural adaptation. An alternative splice variant, the GRbeta (GRbeta) isoform, does not bind ligand and has been proposed to inhibit classic GRalpha-mediated transactivation of target genes. Hence, an increased ratio of GRbeta to GRalpha may induce relative corticosteroid-resistance, as e.g. presumed to occur in major depression. To investigate whether GRbeta is involved in the human hippocampus, we studied GRalpha and GRbeta expression levels in postmortem hippocampal tissue of control subjects by quantitative PCR (Taqman RT-PCR) and immunocytochemistry. Taqman RT-PCR demonstrated a very low relative abundance of GRbeta in the human hippocampus (GRalpha:GRbeta ratio approximately 14,500:1). Immunohistochemical analysis confirmed the occurrence of isolated profiles indeed displaying nuclear staining in the main hippocampal subregions. Subsequent double immunofluorescent analysis revealed that >98% of these GRbeta positive cells were double positive for leucocyte common antigen, that identifies exclusively blood-derived cells of haematopoietic origin, including microglia. We conclude that GRbeta is present in very low amounts in the control human hippocampus, and that of these low numbers of cells, notably, almost all are derived from blood which is inevitably present in postmortem tissue. A functionally relevant role for the GRbeta in control of the human hippocampus is therefore not very likely. Whether this is altered in disease conditions awaits further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0169-328x(03)00209-2DOI Listing
August 2003