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Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.

Memory consolidation is the process of translating memory traces from the hippocampus to the cortex. Hippocampal ripples are key in driving this transfer. A new study now shows that independent cortical ripples can suppress this communication. What could be the underlying mechanisms? [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Hippocampome.org. 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. By integrating single-cell firing behavior during in vivo oscillations with morphological and molecular neuron classification in vitro, this study standardizes a framework for interpreting the functional roles of distinct circuit modules and ascribing extracellular recordings to identified neuron types. [ABSTRACT FROM AUTHOR]

In this issue of Neuron , Petersen et al. (2021) introduce CellExplorer, an open-source tool to integrate neurophysiological metrics of neuronal activity from circuits to behavior. Together with other neuroinformatic resources, it may facilitate community-based multidisciplinary characterization of brain cell types. [ABSTRACT FROM AUTHOR]

Hippocampal place cells receive a disparate collection of excitatory and inhibitory currents that endow them with spatially selective discharges and rhythmic activity. Using a combination of in vivo intracellular and extracellular recordings with opto/chemogenetic manipulations and computational modeling, we investigate the influence of inhibitory and excitatory inputs on CA1 pyramidal cell responses. At the cell bodies, inhibition leads and is stronger than excitation across the entire theta cycle. Pyramidal neurons fire on the ascending phase of theta when released from inhibition. Computational models equipped with the observed conductances reproduce these dynamics. In these models, place field properties are favored when the increased excitation is coupled with a reduction of inhibition within the field. As predicted by our simulations, firing rate within place fields and phase locking to theta are impaired by DREADDs activation of interneurons. Our results indicate that decreased inhibitory conductance is critical for place field expression. [Display omitted] • Inhibition dominates over excitation during theta oscillations in the CA1 region • Concerted excitation/disinhibition favors place field properties in simulations • DREADDs activation of interneurons impairs place field features in CA1 • A transient decrease of inhibition is critical for place field expression Valero et al. examine the influence of inhibition on place fields. They show that hippocampal neurons are dominated by inhibitory conductances during theta oscillations. A transient increase of excitation and drop of inhibition mediates place field emergence in simulations. Consistently, chemogenetic activation of interneurons deteriorates place cell properties in vivo. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Superficial CA1 pyramidal neurons are overactive in epileptic rodents • Neurodegeneration-related gene signatures progress radially in the epileptic CA1 • Larger vulnerability of superficial CA1 pyramidal cells in experimental epilepsy • Cell-type-specific disease trajectories characterize hippocampal sclerosis Cid et al. use a combination of techniques from single-cell recordings in vivo to bulk tissue and single-nucleus RNA-seq to reveal cell-type-specific segregation of neurodegenerative and epileptogenic processes in experimental epilepsy. They find that segregated disease-specific gene expression changes run differentially across cell types and sublayers of the hippocampal CA1 region. [ABSTRACT FROM AUTHOR]

• Relating the activity and morphology of single-cells in vivo is challenging. • Glass micropipettes are the tool of excellence. • Juxtacellular, intracellular and patch-clamp approaches are exploited. • Multiplexed analysis enables unique identification of specific cell-types. • Challenging current approaches is key for new technologies to emerge. Targeting individual neurons in vivo is a key method to study the role of single cell types within local and brain-wide microcircuits. While novel technological developments now permit assessing activity from large number of cells simultaneously, there is currently no better solution than glass micropipettes to relate the physiology and morphology of single-cells. Sharp intracellular, juxtacellular, loose-patch and whole-cell approaches are some of the configurations used to record and label individual neurons. Here, we review procedures to establish successful electrophysiological recordings in vivo followed by appropriate labeling for post hoc morphological analysis. We provide operational recommendations for optimizing each configuration and a generic framework for functional, neurochemical and morphological identification of the different cell-types in a given region. Finally, we highlight emerging approaches that are challenging our current paradigms for single-cell recording and labeling in the living brain. [ABSTRACT FROM AUTHOR]

Bulk-tissue RNA-seq is widely used to dissect variation in gene expression levels across tissues and under different experimental conditions. Here, we introduce a protocol that leverages existing single-cell expression data to deconvolve patterns of cell-type-specific gene expression in differentially expressed gene lists from highly heterogeneous tissue. We apply this protocol to interrogate cell-type-specific gene expression and variation in cell type composition between the distinct sublayers of the hippocampal CA1 region of the brain in a rodent model of epilepsy. For complete details on the use and execution of this protocol, please refer to Cid et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sharp-wave ripples are complex neurophysiological events recorded along the trisynaptic hippocampal circuit (i.e. from CA3 to CA1 and the subiculum) during slow-wave sleep and awake states. They arise locally but scale brain-wide to the hippocampal target regions at cortical and subcortical structures. During these events, neuronal firing sequences are replayed retrospectively or prospectively and in the forward or reverse order as defined by experience. They could reflect either pre-configured firing sequences, learned sequences or an option space to inform subsequent decisions. How can different sequences arise during sharp-wave ripples? Emerging data suggest the hippocampal circuit is organized in different loops across the proximal (close to dentate gyrus) and distal (close to entorhinal cortex) axis. These data also disclose a so-far neglected laminar organization of the hippocampal output during sharp-wave events. Here, I discuss whether by incorporating cell-type-specific mechanisms converging on deep and superficial CA1 sublayers along the proximodistal axis, some novel factors influencing the organization of hippocampal sequences could be unveiled. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.