Guilherme Neves

Guilherme Neves
King's College London | KCL · MRC Centre for Neurodevelopmental Disorders - Institute of Psychiatry, Psychology & Neuroscience

PhD

About

36
Publications
6,628
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2,769
Citations
Introduction
I study the development and function of neural networks. I use molecular biological techniques to perform very precise manipulations in combination with electrophysiology and imaging analysis at cellular resolution. Recently I discovered how increased neural activity reduces developmental apoptosis of inhibitory interneurons. My next project is aimed at applying these insights into the development of new therapies for childhood epilepsy syndromes.

Publications

Publications (36)
Preprint
Full-text available
Electron microscopy is essential for the quantitative study of synaptic ultrastructure. At present, the correlation of functional and structural properties of the same synapse is extremely challenging. We introduce a novel integrated workflow designed to simplify sample navigation across spatial scales, allowing the identification of individual syn...
Preprint
Full-text available
A balance between excitation and inhibition is crucial for neurotypical brain function. Indeed, disruptions in this relationship are frequently associated with the pathophysiology of neurodevelopmental disorders. Nevertheless, how this balance is established during the dynamic period of neurodevelopment remains unexplored. Using multiple techniques...
Article
Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block-face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitator...
Preprint
Full-text available
Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitator...
Preprint
Full-text available
Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in a human iPSC model of ALS. We found that early (6-week) ALS-related TDP-43 G298S motor neurons show...
Article
Full-text available
COVID-19 is a disease with unique characteristics including lung thrombosis1, frequent diarrhoea2, abnormal activation of the inflammatory response3 and rapid deterioration of lung function consistent with alveolar oedema4. The pathological substrate for these findings remains elusive. Here we show that the lungs of patients with COVID-19 contain i...
Article
Full-text available
The activity-dependent rules that govern the wiring of GABAergic interneurons are not well understood. Chandelier cells (ChCs) are a type of GABAergic interneuron that control pyramidal cell output through axo-axonic synapses that target the axon initial segment. In vivo imaging of ChCs during development uncovered a narrow window (P12–P18) over wh...
Data
Compartmental model of dendritic integration that implements synaptic short-term facilitation and depression as described previously (Varela et al., 1997). Simulations were performed with the NEURON simulation environment (Hines and Carnevale, 1997).
Article
Full-text available
The mammalian cortex consists of two main neuronal types: the principal excitatory pyramidal neurons (PNs) and the inhibitory interneurons (INs). The interplay between these two neuronal populations – which drive excitation and inhibition (E/I balance), respectively – is crucial for controlling the overall activity in the brain. A number of neurolo...
Article
Full-text available
How presynaptic inputs and neurotransmitter release dynamics are distributed along a dendritic tree is not well established. Here, we show that presynaptic boutons that form onto basal dendrites of CA1 pyramidal neurons display a decrease in active zone (AZ) size with distance from the soma, resulting in a distance-dependent increase in short-term...
Article
Full-text available
Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generate...
Article
Significance Neurons in the brain extend long dendrites that are packed with small protrusions, or spines, responsible for receiving information from presynaptic axons. Although we know much about the workings of spines, we know little about the large-scale distribution of the properties of these compartments along dendritic trees. Here, we provide...
Article
Full-text available
Deletion of LIM homeodomain transcription factor-encoding Lhx6 gene in mice results in defective tangential migration of cortical interneurons and failure of differentiation of the somatostatin (Sst)- and parvalbumin (Pva)-expressing subtypes. Here, we characterize a novel hypomorphic allele of Lhx6 and demonstrate that reduced activity of this loc...
Article
Full-text available
The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodom...
Article
Full-text available
Two facts about the hippocampus have been common currency among neuroscientists for several decades. First, lesions of the hippocampus in humans prevent the acquisition of new episodic memories; second, activity-dependent synaptic plasticity is a prominent feature of hippocampal synapses. Given this background, the hypothesis that hippocampus-depen...
Article
Full-text available
Drosophila N-cadherin (CadN) is an evolutionarily conserved classic cadherin which has a large, complex extracellular domain and a catenin-binding cytoplasmic domain. The CadN locus contains three modules of alternative exons (7a/b, 13a/b, and 18a/b) and undergoes alternative splicing to generate multiple isoforms. Using quantitative transcript ana...
Article
Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the...
Article
Full-text available
The Drosophila melanogaster gene Dscam is essential for axon guidance and has 38,016 possible alternative splice forms. This diversity can potentially be used to distinguish cells. We analyzed the Dscam mRNA isoforms expressed by different cell types and individual cells. The choice of splice variants expressed is regulated both spatially and tempo...
Article
Full-text available
Excerpt Clearly, gene regulation (the turning on and off of themultitudinous genes in the genome) allows the specification of different parts of the nervous system as it allowsspecification of all parts of the developing animal. Evenwithin a group of neurons, distinguishing similar neuronsalso can be accomplished by the specific turning on andoff o...
Article
Calcium-triggered exocytosis at the synapse is suppressed by addition of calcium chelators, but the effects of endogenous Ca(2+) buffers have not been tested. We find that 80% of Ca(2+) binding sites in the synaptic terminal of retinal bipolar cells were associated with mobile molecules that suppressed activation of Ca(2+)-sensitive K(+) channels w...
Article
Full-text available
To investigate the regulation of endocytosis by Ca(2+), we have made capacitance measurements in the synaptic terminal of depolarizing bipolar cells from the retina of goldfish. After a brief depolarization, all of the excess membrane was retrieved rapidly (tau approximately 1 s). But when the rise in free [Ca(2+)] was reduced by the introduction o...
Article
1. We investigated the properties of Ca2+-sensitive steps in the cycling of synaptic vesicles by comparing the actions of Ca2+, Ba2+ and Sr2+ in the synaptic terminal of depolarizing bipolar cells isolated from the retina of goldfish. FM1-43 fluorescence and capacitance measurements demonstrated that exocytosis, endocytosis and vesicle mobilization...
Article
Ganglion cells convey information from the retina back to the brain. Recent experiments have examined how ganglion cell receptive fields are assembled from many incoming signals.
Article
1. The kinetics of exocytosis and endocytosis were studied in the giant synaptic terminal of depolarizing bipolar cells from the goldfish retina. Two techniques were applied: capacitance measurements of changes in membrane surface area, and fluorescence measurements of exocytosis using the membrane dye FM1-43. 2. Three phases of exocytosis occurred...

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