Publications by authors named "Alexander P Y Brown"

7 Publications

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Analysis of segmentation ontology reveals the similarities and differences in connectivity onto L2/3 neurons in mouse V1.

Sci Rep 2021 Mar 2;11(1):4983. Epub 2021 Mar 2.

Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, 25 Howland Street, London, W1T 4JG, UK.

Quantitatively comparing brain-wide connectivity of different types of neuron is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine and compare datasets from hierarchical segmentation ontologies, and applied it to long-range presynaptic connectivity onto excitatory and inhibitory neurons, mainly located in layer 2/3 (L2/3), of mouse primary visual cortex (V1). We find that the origins of long-range connections onto these two general cell classes-as well as their proportions-are quite similar, in contrast to the inputs on to a cell type in L6. These anatomical data suggest that distal inputs received by the general excitatory and inhibitory classes of neuron in L2/3 overlap considerably.
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http://dx.doi.org/10.1038/s41598-021-82353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925549PMC
March 2021

Visual Experience Regulates the Intrinsic Excitability of Visual Cortical Neurons to Maintain Sensory Function.

Cell Rep 2019 04;27(3):685-689.e4

The Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, 25 Howland Street, London W1T 4JG, UK. Electronic address:

This in vivo study shows that both intrinsic and sensory-evoked synaptic properties of layer 2/3 neurons in mouse visual cortex are modified by ongoing visual input. Following visual deprivation, intrinsic properties are significantly altered, although orientation selectivity across the population remains unchanged. We, therefore, suggest that cortical cells adjust their intrinsic excitability in an activity-dependent manner to compensate for changes in synaptic drive and maintain sensory network function.
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http://dx.doi.org/10.1016/j.celrep.2019.03.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484778PMC
April 2019

Silicon Valley new focus on brain computer interface: hype or hope for new applications?

F1000Res 2018 21;7:1327. Epub 2018 Aug 21.

Department of Neurosurgery, Stanford University Medical Center, Brighton, USA.

In the last year there has been increasing interest and investment into developing devices to interact with the central nervous system, in particular developing a robust brain-computer interface (BCI). In this article, we review the most recent research advances and the current host of engineering and neurological challenges that must be overcome for clinical application. In particular, space limitations, isolation of targeted structures, replacement of probes following failure, delivery of nanomaterials and processing and understanding recorded data. Neural engineering has developed greatly over the past half-century, which has allowed for the development of better neural recording techniques and clinical translation of neural interfaces. Implementation of general purpose BCIs face a number of constraints arising from engineering, computational, ethical and neuroscientific factors that still have to be addressed. Electronics have become orders of magnitude smaller and computationally faster than neurons, however there is much work to be done in decoding the neural circuits. New interest and funding from the non-medical community may be a welcome catalyst for focused research and development; playing an important role in future advancements in the neuroscience community.
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http://dx.doi.org/10.12688/f1000research.15726.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343225PMC
November 2019

aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data.

Nat Commun 2016 07 7;7:11879. Epub 2016 Jul 7.

The Division of Neurophysiology, MRC National Institute for Medical Research, London NW7 1AA, UK.

The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain.
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http://dx.doi.org/10.1038/ncomms11879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941048PMC
July 2016

Patch clamp.

Br J Hosp Med (Lond) 2016 May;77(5):C74-7

PhD Student, Cardiovascular and Cell Sciences Institute, St. George's University of London, London.

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http://dx.doi.org/10.12968/hmed.2016.77.5.C74DOI Listing
May 2016

The stimulus selectivity and connectivity of layer six principal cells reveals cortical microcircuits underlying visual processing.

Neuron 2014 Sep 28;83(6):1431-43. Epub 2014 Aug 28.

The Division of Neurophysiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address:

Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.
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http://dx.doi.org/10.1016/j.neuron.2014.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175007PMC
September 2014