Human neuropathology confirms projection neuron and interneuron defects and delayed oligodendrocyte production and maturation in FOXG1 syndrome

AbstractThe physical distance between presynaptic Ca2+ channels and the Ca2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca2+ channels and the (m)unc13 family priming factors, Unc13A and Unc13B. Importantly, coupling distance defines release components with distinct STP characteristics. Here, we show that while Unc13A and Unc13B both contribute to synaptic signalling, they play distinct roles in neural decoding of olfactory information at excitatory projection neuron (ePN) output synapses. Unc13A clusters closer to Ca2+ channels than Unc13B, specifically promoting fast phasic signal transfer. Reduction of Unc13A in ePNs attenuates responses to both aversive and appetitive stimuli, while reduction of Unc13B provokes a general shift towards appetitive values. Collectively, we provide direct genetic evidence that release components of distinct nanoscopic coupling distances differentially control STP to play distinct roles in neural decoding of sensory information.

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The role of elevated levels of microRNA-155-5p and microRNA-124-5p in hyperuricemia and acute ischemic stroke

Materials Express ◽

10.1166/mex.2021.2080 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1674-1680

Author(s):

Yuan Yao ◽

Jun Yuan ◽

Yanju Ma ◽

Runxiu Zhu ◽

Yong Ma

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Application ◽

Cerebral Vasospasm ◽

Rat Model ◽

Inner Mongolia ◽

Neuronal Apoptosis ◽

Projection Neuron ◽

Neuron Differentiation

Hyperuricemia is closely related to acute ischemic stroke (AIS). In our study, we investigated the pattern of miRNA-155-5p and miRNA-124-5p expressions along with its clinical application in AIS and hyperuricemia patients and in a hyperuricemia rat model by RT-qPCR. The hyperuricemia rat model was established, and we found that the levels of miRNA-155-5p and miRNA-124-5p were increased in the serum, brain and kidney tissues compared with those in the normal rats. We proved that the levels of miRNA-155-5p and miRNA-124-5p were also elevated in AIS, hyperuricemia and AIS accompanied with hyperuricemia patients enrolled from the department of neurology in Inner Mongolia People’s Hospital (IMPH). The miRNA-155-5p and miRNA-124-5p were mainly associated with neuronal apoptosis, cerebral vasospasm, neuron projection, neuron projection morphogenesis, neuron differentiation and exocytosis. The above results might provide clues for the study the pathogenesis of AIS and hyperuricemia.

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Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain

Journal of Neurophysiology ◽

10.1152/jn.90835.2008 ◽

2009 ◽

Vol 101 (2) ◽

pp. 591-602 ◽

Cited By ~ 4

Author(s):

Hiraku Mochida ◽

Gilles Fortin ◽

Jean Champagnat ◽

Joel C. Glover

Keyword(s):

Spontaneous Activity ◽

Projection Neuron ◽

Projection Neurons ◽

Charge Coupled Device ◽

Neuron Populations ◽

Motor Nerves ◽

Differential Involvement ◽

A Charge ◽

The Brain ◽

Calcium Green

To better characterize the emergence of spontaneous neuronal activity in the developing hindbrain, spontaneous activity was recorded optically from defined projection neuron populations in isolated preparations of the brain stem of the chicken embryo. Ipsilaterally projecting reticulospinal (RS) neurons and several groups of vestibuloocular (VO) neurons were labeled retrogradely with Calcium Green-1 dextran amine and spontaneous calcium transients were recorded using a charge-coupled-device camera mounted on a fluorescence microscope. Simultaneous extracellular recordings were made from one of the trigeminal motor nerves (nV) to register the occurrence of spontaneous synchronous bursts of activity. Two types of spontaneous activity were observed: synchronous events (SEs), which occurred in register with spontaneous bursts in nV once every few minutes and were tetrodotoxin (TTX) dependent, and asynchronous events (AEs), which occurred in the intervals between SEs and were TTX resistant. AEs occurred developmentally before SEs and were in general smaller and more variable in amplitude than SEs. SEs appeared at the same stage as nV bursts early on embryonic day 4, first in RS neurons and then in VO neurons. All RS neurons participated equally in SEs from the outset, whereas different subpopulations of VO neurons participated differentially, both in terms of the proportion of neurons that exhibited SEs, the fidelity with which the SEs in individual neurons followed the nV bursts, and the developmental stage at which SEs appeared and matured. The results show that spontaneous activity is expressed heterogeneously among hindbrain projection neuron populations, suggesting its differential involvement in the formation of different functional neuronal circuits.

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FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

eLife ◽

10.7554/elife.42012 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Ryan J Kast ◽

Alexandra L Lanjewar ◽

Colton D Smith ◽

Pat Levitt

Keyword(s):

Expression Patterns ◽

Projection Neuron ◽

Specific Expression ◽

Neuron Populations ◽

Mouse Cortex ◽

Molecular Studies ◽

Multiple Species ◽

Molecular Phenotypes ◽

And Function

The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.

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Development and Regeneration of Projection Neuron Subtypes of the Cerebral Cortex

Science Progress ◽

10.3184/003685010x12705764469952 ◽

2010 ◽

Vol 93 (2) ◽

pp. 151-169 ◽

Cited By ~ 5

Author(s):

Giulio Srubek Tomassy ◽

Simona Lodato ◽

Zachary Trayes-Gibson ◽

Paola Arlotta

Keyword(s):

Cerebral Cortex ◽

Projection Neuron

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Excitatory Projection Neuron Subtypes Control the Distribution of Local Inhibitory Interneurons in the Cerebral Cortex

Neuron ◽

10.1016/j.neuron.2011.01.015 ◽

2011 ◽

Vol 69 (4) ◽

pp. 763-779 ◽

Cited By ~ 122

Author(s):

Simona Lodato ◽

Caroline Rouaux ◽

Kathleen B. Quast ◽

Chanati Jantrachotechatchawan ◽

Michèle Studer ◽

...

Keyword(s):

Cerebral Cortex ◽

Projection Neuron ◽

Inhibitory Interneurons ◽

Excitatory Projection

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Tonic engagement of nicotinic receptors bidirectionally controls striatal spiny projection neuron spike timing

10.1101/2021.11.02.466870 ◽

2021 ◽

Author(s):

Lior Matityahu ◽

Jeffrey Malgady ◽

Meital Schirelman ◽

Yvonne Johansson ◽

Jennifer Wilking ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Gaba Release ◽

Projection Neuron ◽

Spike Timing ◽

Projection Neurons ◽

Striatal Slices ◽

Cholinergic Interneurons ◽

Α7 Nachr ◽

Α7 Nachrs

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can 1) disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs and 2) directly modulate corticostriatal synaptic strength via pre-synaptic α7 nAChR receptors. Measurements of the disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that do not respond to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections, blockade of α7 nAChRs delayed SPN spikes, whereas blockade of α4β2 nAChRs advanced SPN spikes and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond to phasic CIN activation. In particular, the observed spike-advancement caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, and a parallel hyperpolarization of PV-FSIs. Taken together, we describe opposing roles for tonic (as opposed to phasic) engagement of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs both sharpens the temporal fidelity of corticostriatal signaling via pre-synaptic α7 nAChRs and maintains a GABAergic brake on cortically-driven striatal output, processes that may shape SPN spike timing, striatal processing and synaptic plasticity.

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Differential timing of a conserved transcriptional network underlies divergent cortical projection routes across mammalian brain evolution

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1922422117 ◽

2020 ◽

Vol 117 (19) ◽

pp. 10554-10564 ◽

Cited By ~ 5

Author(s):

Annalisa Paolino ◽

Laura R. Fenlon ◽

Peter Kozulin ◽

Elizabeth Haines ◽

Jonathan W. C. Lim ◽

...

Keyword(s):

Transcription Factor ◽

Corpus Callosum ◽

Anterior Commissure ◽

Regulatory Gene ◽

Brain Evolution ◽

Projection Neuron ◽

Egg Laying ◽

Mammalian Brain ◽

Transcriptional Networks ◽

Cortical Projection

A unique combination of transcription factor expression and projection neuron identity demarcates each layer of the cerebral cortex. During mouse and human cortical development, the transcription factor CTIP2 specifies neurons that project subcerebrally, while SATB2 specifies neuronal projections via the corpus callosum, a large axon tract connecting the two neocortical hemispheres that emerged exclusively in eutherian mammals. Marsupials comprise the sister taxon of eutherians but do not have a corpus callosum; their intercortical commissural neurons instead project via the anterior commissure, similar to egg-laying monotreme mammals. It remains unknown whether divergent transcriptional networks underlie these cortical wiring differences. Here, we combine birth-dating analysis, retrograde tracing, gene overexpression and knockdown, and axonal quantification to compare the functions of CTIP2 and SATB2 in neocortical development, between the eutherian mouse and the marsupial fat-tailed dunnart. We demonstrate a striking degree of structural and functional homology, whereby CTIP2 or SATB2 of either species is sufficient to promote a subcerebral or commissural fate, respectively. Remarkably, we reveal a substantial delay in the onset of developmental SATB2 expression in mice as compared to the equivalent stage in dunnarts, with premature SATB2 overexpression in mice to match that of dunnarts resulting in a marsupial-like projection fate via the anterior commissure. Our results suggest that small alterations in the timing of regulatory gene expression may underlie interspecies differences in neuronal projection fate specification.

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