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      Classification of Cortical Neurons by Spike Shape and the Identification of Pyramidal Neurons

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          Abstract

          Many investigators who make extracellular recordings from populations of cortical neurons are now using spike shape parameters, and particularly spike duration, as a means of classifying different neuronal sub-types. Because of the nature of the experimental approach, particularly that involving nonhuman primates, it is very difficult to validate directly which spike characteristics belong to particular types of pyramidal neurons and interneurons, as defined by modern histological approaches. This commentary looks at the way antidromic identification of pyramidal cells projecting to different targets, and in particular, pyramidal tract neurons (PTN), can inform the utility of spike width classification. Spike duration may provide clues to a diversity of function across the pyramidal cell population, and also highlights important differences that exist across species. Our studies suggest that further electrophysiological and optogenetic approaches are needed to validate spike duration as a means of cell classification and to relate this to well-established histological differences in neocortical cell types.

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          Most cited references69

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          Fully integrated silicon probes for high-density recording of neural activity

          Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.
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            GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits.

            Cortical networks are composed of glutamatergic excitatory projection neurons and local GABAergic inhibitory interneurons that gate signal flow and sculpt network dynamics. Although they represent a minority of the total neocortical neuronal population, GABAergic interneurons are highly heterogeneous, forming functional classes based on their morphological, electrophysiological, and molecular features, as well as connectivity and in vivo patterns of activity. Here we review our current understanding of neocortical interneuron diversity and the properties that distinguish cell types. We then discuss how the involvement of multiple cell types, each with a specific set of cellular properties, plays a crucial role in diversifying and increasing the computational power of a relatively small number of simple circuit motifs forming cortical networks. We illustrate how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.
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              Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex.

              Slices of sensorimotor and anterior cingulate cortex from guinea pigs were maintained in vitro and bathed in a normal physiological medium. Electrophysiological properties of neurons were assessed with intracellular recording techniques. Some neurons were identified morphologically by intracellular injection of the fluorescent dye Lucifer yellow CH. Three distinct neuronal classes of electrophysiological behavior were observed; these were termed regular spiking, bursting, and fast spiking. The physiological properties of neurons from sensorimotor and anterior cingulate areas did not differ significantly. Regular-spiking cells were characterized by action potentials with a mean duration of 0.80 ms at one-half amplitude, a ratio of maximum rate of spike rise to maximum rate of fall of 4.12, and a prominent afterhyperpolarization following a train of spikes. The primary slope of initial spike frequency versus injected current intensity was 241 Hz/nA. During prolonged suprathreshold current pulses the frequency of firing adapted strongly. When local synaptic pathways were activated, all cells were transiently excited and then strongly inhibited. Bursting cells were distinguished by their ability to generate endogenous, all-or-none bursts of three to five action potentials. Their properties were otherwise very similar to regular-spiking cells. The ability to generate a burst was eliminated when the membrane was depolarized to near the firing threshold with tonic current. By contrast, hyperpolarization of regular-spiking (i.e., nonbursting) cells did not uncover latent bursting tendencies. The action potentials of fast-spiking cells were much briefer (mean of 0.32 ms) than those of the other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                Journal
                Cereb Cortex
                Cereb Cortex
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                November 2021
                12 June 2021
                12 June 2021
                : 31
                : 11
                : 5131-5138
                Affiliations
                Department of Clinical and Movement Neurosciences , UCL Queen Square Institute of Neurology , London WC1N 3BG, UK
                Biosciences Institute , Newcastle University , Newcastle upon Tyne NE2 4HH, UK
                Biosciences Institute , Newcastle University , Newcastle upon Tyne NE2 4HH, UK
                Author notes
                Address for correspondence to Alexander Kraskov, Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Email: alexander.kraskov@ 123456ncl.ac.uk
                Article
                bhab147
                10.1093/cercor/bhab147
                8491674
                34117760
                016add32-4f03-4547-b9e2-87d3a79d2a51
                © The Author(s) 2021. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 8
                Funding
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: 02849/Z/13/Z
                Funded by: BBSRC, DOI 10.13039/501100000268;
                Award ID: BB/P006027/1
                Funded by: Medical Research Council, DOI 10.13039/501100007155;
                Award ID: MR/P012922/1
                Award ID: MR/P023967/1
                Funded by: NIH, DOI 10.13039/100000002;
                Award ID: 1R01NS119319-01
                Categories
                Feature Article
                AcademicSubjects/MED00310
                AcademicSubjects/MED00385
                AcademicSubjects/SCI01870

                Neurology
                antidromic,cell types classification,interneurons,pyramidal,spike shape
                Neurology
                antidromic, cell types classification, interneurons, pyramidal, spike shape

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