Emergent dynamics of fast ripples in the epileptic hippocampus

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in >pure> fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in >emergent> fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo.We found that in-phase firing can reach frequencies up to 300 Hz in the CA1and up to 400Hzin the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus. Copyright © 2010 the authors.Peer Reviewe

Immunohistochemical field parcellation of the human hippocampus along its antero-posterior axis

The primate hippocampus includes the dentate gyrus, cornu ammonis (CA), and subiculum. CA is subdivided into four felds (CA1-CA3, plus CA3h/hilus of the dentate gyrus) with specifc pyramidal cell morphology and connections. Work in non-human mammals has shown that hippocampal connectivity is precisely patterned both in the laminar and longitudinal axes. One of the main handicaps in the study of neuropathological semiology in the human hippocampus is the lack of clear laminar and longitudinal borders. The aim of this study was to explore a histochemical segmentation of the adult human hippocampus, integrating feld (medio-lateral), laminar, and anteroposterior longitudinal patterning. We provide criteria for head-body-tail feld and subfeld parcellation of the human hippocampus based on immunodetection of Rabphilin3a (Rph3a), Purkinje-cell protein 4 (PCP4), Chromogranin A and Regulation of G protein signaling-14 (RGS-14). Notably, Rph3a and PCP4 allow to identify the border between CA3 and CA2, while Chromogranin A and RGS-14 give specifc staining of CA2. We also provide novel histological data about the composition of human-specifc regions of the anterior and posterior hippocampus. The data are given with stereotaxic coordinates along the longitudinal axis. This study provides novel insights for a detailed region-specifc parcellation of the human hippocampus useful for human brain imaging and neuropathologyOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. EG-A, IP-S and CC were the recipients of grants from the Chair in Neuroscience UAM-Fundación Tatiana Pérez de Guzmán el Bueno (Spain), and from thePlan Propio de Investigaciónof the University of La Laguna. LMP was the recipient of grant PID2021-124829NB-I00 from the Ministry of Science and Innovation of Spai

Plasmonics on a Neural Implant: Engineering Light–Matter Interactions on the Nonplanar Surface of Tapered Optical Fibers

Optical methods are driving a revolution in neuroscience. Ignited by optogenetic techniques, a set of strategies has emerged to control and monitor neural activity in deep brain regions using implantable photonic probes. A yet unexplored technological leap is exploiting nanoscale light-matter interactions for enhanced bio-sensing, beam-manipulation and opto-thermal heat delivery in the brain. To bridge this gap, we got inspired by the brain cells’ scale to propose a nano-patterned tapered-fiber neural implant featuring highly-curved plasmonic structures (30 μm radius of curvature, sub-50 nm gaps). We describe the nanofabrication process of the probes and characterize their optical properties. We suggest a theoretical framework using the interaction between the guided modes and plasmonic structures to engineer the electric field enhancement at arbitrary depths along the implant, in the visible/near-infrared range. We show that our probes can control the spectral and angular patterns of optical transmission, enhancing the angular emission and collection range beyond the reach of existing optical neural interfaces. Finally, we evaluate the application as fluorescence and Raman probes, with wave-vector selectivity, for multimodal neural applications. We believe our work represents a first step towards a new class of versatile nano-optical neural implants for brain research in health and disease.M.D.V., M.G., and Fe.P. jointly supervised and are co-last authors in this work. Fi.P., A.B., and Fe.P. acknowledge funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 677683. F.D.A., L.M.d.l.P., M.V., M.D.V., and Fe.P. acknowledge funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 828972. Fi.P., M.D.V., and Fe.P. acknowledge that this project has received funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 101016787. M.P., Fe.P., and M.D.V. were funded by the U.S. National Institutes of Health (Grant No. 1UF1NS108177-01). Open access funding provided by Istituto Italiano di Tecnologia within the CRUI-CARE agreemen

Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations

Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for flexible dynamical representations of theta sequences

Holographic Manipulation of Nanostructured Fiber Optics Enables Spatially-Resolved, Reconfigurable Optical Control of Plasmonic Local Field Enhancement and SERS

Integration of plasmonic structures on step-index optical fibers is attracting interest for both applications and fundamental studies. However, the possibility to dynamically control the coupling between the guided light fields and the plasmonic resonances is hindered by the turbidity of light propagation in multimode fibers (MMFs). This pivotal point strongly limits the range of studies that can benefit from nanostructured fiber optics. Fortunately, harnessing the interaction between plasmonic modes on the fiber tip and the full set of guided modes can bring this technology to a next generation progress. Here, the intrinsic wealth of information of guided modes is exploited to spatiotemporally control the plasmonic resonances of the coupled system. This concept is shown by employing dynamic phase modulation to structure both the response of plasmonic MMFs on the plasmonic facet and their response in the corresponding Fourier plane, achieving spatial selective field enhancement and direct control of the probe's work point in the dispersion diagram. Such a conceptual leap would transform the biomedical applications of holographic endoscopic imaging by integrating new sensing and manipulation capabilities.L.C. and Fi.P. contributed equally to this work. M.D.V. and Fe.P. jointly supervised and are co-last authors of this work. L.C., D.Z., L.M.P., C.C., M.D.V., and Fe.P. acknowledge European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 828972. Fi.P., A.B., and Fe.P. acknowledge European Research Council under the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 677683. Fi.P., M.D.V., and Fe.P. acknowledge European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No 101016787. M.P. and M.D.V. acknowledge European Research Council under the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. 692943. M.P., Fe.P., and M.D.V. acknowledge U.S. National Institutes of Health (Grant No. 1UF1NS108177-01). M.D.V. acknowledges U.S. National Institutes of Health (Grant No. U01NS094190)

An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo

Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal-hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in . We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.Peer reviewe

Challenge 2: From genes & circuits to behavior

Understanding the brain from genes and circuits to behavior is a major scientific challenge. The large repertoire of cell activities supporting behavior stems from an equally diverse range of specialized cell types, from neuron to glia. To untangle mechanisms underlying brain function, elementary processes should be dissected, from the complex machinery of signaling pathways at the level of single cells and synapses, to the intricate phenomena leading to orchestrated ensemble activity and the establishment of engrams driving memory-guided behaviors. In this chapter we identify the main key tasks required to address some of the open questions in the field, and discuss on the main issues and strategies

White Paper 5: Brain, Mind & Behaviour

© CSICThe study of the brain will tell us what makes us humans and how our social behavior generates. Increasing our understanding of how the brain functions and interacts with the ecosystem to interpret the world will not only help to find effective means to treat and/or cure neurological and psychiatric disorders but will also change our vision on questions pertaining to philosophy and humanities and transform other fields such as economy and law. Neurosciences research at the CSIC is already valuable and should be intensified mainly focused on the eight major challenges described in this volume

Neuronal Shot Noise and Brownian 1/f21/f^2 Behavior in the Local Field Potential

We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous $1/f^2$ scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this $1/f^2$ Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose extracellular fields slowly decay and 2) rapidly firing, temporally correlated cells that generate UP-DOWN states

Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents. Bulk tissue and single-nucleus expression profiling disclose sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage channels, synaptic signaling, and cell adhesion are deregulated differently by epilepsy across sublayers, whereas neurodegenerative signatures primarily involve superficial cells. Pseudotime analysis of gene expression in single nuclei and in situ validation reveal separated trajectories from health to epilepsy across cell types and identify a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate that sublayer- and cell-type-specific changes associated with selective CA1 neuronal damage contribute to progression of hippocampal sclerosis.This work was supported by grants from MICINN (RTI2018-098581-B-I00 to L.M.P.), Fundación Tatiana Pérez de Guzman el Bueno, and the SynCogDis Network (SAF2014-52624-REDT and SAF2017- 90664-REDT to L.M.P. and A. Bayes). Collaboration between L.M.d.l.P. and Y.H. was supported by Human Frontiers Science Program (HFSP) grant RGP0022/2013. J.P.L.-A. was supported by grants from MICIU co-financed by ERDF (RYC-2015-18056 and RTI2018-102260-B-I00) and Severo Ochoa grant SEV-2017-0723. R.R.-V. and A. Bayes were supported by MINECO BFU2015-69717-P and RTI2018-097037-B-100 and a Marie Curie career integration grant (ref. 304111). A.V.M. was supported by MICINN (SAF2017- 85717-R) and Fundación Alicia Koplowitz. A. Barco was supported by grants SAF2017-87928-R from MICINN co-financed by ERDF and RGP0039/2017 from the Human Frontiers Science Program Organization. The Instituto de Neurociencias is a ‘‘Centre of Excellence Severo Ochoa.’’ D.G.-D. and C.M.N. hold PhD fellowships from MICINN (BES-2013-064171 and BES2016-076281, respectively).Peer reviewe