Developmental Neurobiology 

About: Developmental Neurobiology is an academic journal published by Wiley-Blackwell. The journal publishes majorly in the area(s): Neurogenesis & Axon. It has an ISSN identifier of 1932-8451. Over the lifetime, 1344 publications have been published receiving 47267 citations.

Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons

Abstract: An understanding of the diversity of cortical GABAergic interneurons is critical to understand the function of the cerebral cortex. Recent data suggest that neurons expressing three markers, the Ca2+-binding protein parvalbumin (PV), the neuropeptide somatostatin (SST), and the ionotropic serotonin receptor 5HT3a (5HT3aR) account for nearly 100% of neocortical interneurons. Interneurons expressing each of these markers have a different embryological origin. Each group includes several types of interneurons that differ in morphological and electrophysiological properties and likely have different functions in the cortical circuit. The PV group accounts for ∼40% of GABAergic neurons and includes fast spiking basket cells and chandelier cells. The SST group, which represents ∼30% of GABAergic neurons, includes the Martinotti cells and a set of neurons that specifically target layerIV. The 5HT3aR group, which also accounts for ∼30% of the total interneuronal population, is heterogeneous and includes all of the neurons that express the neuropeptide VIP, as well as an equally numerous subgroup of neurons that do not express VIP and includes neurogliaform cells. The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states and behavioral contexts.

The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity.

Abstract: Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges.

Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease

Abstract: Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that regulates diverse developmental events from the selection of neural progenitors to the terminal dendritic differentiation and connectivity of neurons. We focus here on activity-dependent synaptic regulation by BDNF and its receptor, full length TrkB. BDNF-TrkB signaling is involved in transcription, translation, and trafficking of proteins during various phases of synaptic development and has been implicated in several forms of synaptic plasticity. These functions are carried out by a combination of the three signaling cascades triggered when BDNF binds TrkB: the mitogen-activated protein kinase (MAPK), the phospholipase Cγ (PLC PLCγ), and the phosphatidylinositol 3-kinase (PI3K) pathways. MAPK and PI3K play crucial roles in both translation and/or trafficking of proteins induced by synaptic activity while PLCγ regulates intracellular Ca2+ that can drive transcription via cyclic AMP and a Protein Kinase C. Conversely, the abnormal regulation of BDNF is implicated in various developmental and neurodegenerative diseases that perturb neural development and function. We will discuss the current state of understanding BDNF signaling in the context of synaptic development and plasticity with a focus on the post-synaptic cell and close with the evidence that basic mechanisms of BDNF function still need to be understood in order to effectively treat genetic disruptions of these pathways that cause devastating neurodevelopmental diseases.

Brain-Derived Neurotrophic Factor and the Development of Structural Neuronal Connectivity

Abstract: Neurotrophins are growth factors with crucial roles in the developing and mature nervous system. They are initially synthesized as precursor proteins (pro-neurotrophins), which are processed intracellularly to be secreted mostly in a mature, biologically active form (Mowla et al., 1999; Mowla et al., 2001; Matsumoto et al., 2008; for review see Lu et al., 2005). Pro-neurotrophins can also influence developing and mature neural circuits, and may be released in a developmentally regulated manner (Lee et al., 2001; Lu et al., 2005; Teng et al., 2005; Yang et al., 2009). Neurotrophins bind two classes of membrane receptors, the tropomyosin receptor kinase (Trk) family of receptors and the p75 neurotrophin receptor (p75NTR) (for a review see Chao, 2003). The actions of mature neurotrophins are mediated by the high affinity full-length Trk receptors, which signal through their intrinsic tyrosine kinase activity to promote growth. Trk receptors signal by dimerization of receptor molecules, leading to intracellular phosphorylation and activation of intracellular signaling cascades (Ullrich and Schlessinger, 1990; Jing et al., 1992). Truncated Trk receptors (Trk.T) are splice variants of full-length Trks, which lack the intracellular tyrosine kinase domain, and are thought to act as negative effectors of full-length receptors (Luikart et al., 2003), although they may also have their own signaling properties (Rose et al., 2003; Ohira et al., 2006). The neurotrophins show binding specificity for particular Trk receptors: nerve growth factor (NGF) binds to TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4) to TrkB, and neurotrophin 3 (NT3) to TrkC (Chao, 2003). The p75NTR has low affinity for the mature neurotrophins, but can form a complex with Trk receptors to form high affinity binding sites for neurotrophins, enabling the receptor to participate in the stimulation of growth processes (Esposito et al., 2001). Moreover, p75NTR displays high affinity binding with pro-neurotrophins, and induces apoptosis by interacting with sortilin (Lee et al., 2001; Nykjaer et al., 2004). Thus, pro-neurotrophins and mature neurotrophins may utilize distinct receptors to mediate divergent neuronal actions. This review focuses on the actions of mature BDNF, highlighting the role that BDNF plays in the development of synaptic connectivity in the central nervous system (CNS). Evidence supporting presynaptic actions by target-released BDNF, and the influence that BDNF exerts during the structural development of neurons are reviewed here.

PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation

Abstract: The phosphoinositide 3-OH kinase (PI3K)/Akt pathway has been implicated in regulating several important cellular processes, including apoptosis, survival, proliferation, and metabolism. Using both pharmacological and genetic means, we demonstrate here that PI3K/Akt plays a crucial role in the proliferation of adult hippocampal neural progenitor cells. PI3K/Akt transduces intracellular signals from multiple mitogens, including basic fibroblast growth factor (FGF-2), Sonic hedgehog (Shh), and insulin-like growth factor 1 (IGF-1). In addition, retroviral vector-mediated over-expression of wild type Akt increased cell proliferation, while a dominant negative Akt inhibited proliferation. Furthermore, wild type Akt over-expression reduced glial (GFAP) and neuronal (β-tubulin III) marker expression during differentiation, indicating that it inhibits cell differentiation. We also show that activation of the cAMP response element binding protein (CREB), which occurs in cells stimulated by FGF-2, is limited when Akt signaling is inhibited, demonstrating a link between Akt and CREB. Over-expression of wild type CREB increases progenitor proliferation, whereas dominant negative CREB only slightly decreases proliferation. These results indicate that PI3K/Akt signaling integrates extracellular signaling information to promote cellular proliferation and inhibit differentiation in adult neural progenitors. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.