For each environment a rodent has explored, its hippocampus contains a map consisting of a unique subset of neurons, called place cells, that have spatially tuned spiking there, with the remaining ...neurons being essentially silent. Using whole-cell recording in freely moving rats exploring a novel maze, we observed differences in intrinsic cellular properties and input-based subthreshold membrane potential levels underlying this division into place and silent cells. Compared to silent cells, place cells had lower spike thresholds and peaked versus flat subthreshold membrane potentials as a function of animal location. Both differences were evident from the beginning of exploration. Additionally, future place cells exhibited higher burst propensity before exploration. Thus, internal settings appear to predetermine which cells will represent the next novel environment encountered. Furthermore, place cells fired spatially tuned bursts with large, putatively calcium-mediated depolarizations that could trigger plasticity and stabilize the new map for long-term storage. Our results provide new insight into hippocampal memory formation.
► Inputs to place and silent cells as seen at soma differ from the start of exploration ► Intrinsic properties of place and silent cells differ from the start of exploration ► Large, putatively Ca
2+-based depolarizations occur at the centers of place fields ► These features may underlie formation and long-term storage of hippocampal memories
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Hippocampal activity represents many behaviorally important variables, including context, an animal’s location within a given environmental context, time, and reward. Using longitudinal calcium ...imaging in mice, multiple large virtual environments, and differing reward contingencies, we derived a unified probabilistic model of CA1 representations centered on a single feature—the field propensity. Each cell’s propensity governs how many place fields it has per unit space, predicts its reward-related activity, and is preserved across distinct environments and over months. Propensity is broadly distributed—with many low, and some very high, propensity cells—and thus strongly shapes hippocampal representations. This results in a range of spatial codes, from sparse to dense. Propensity varied ∼10-fold between adjacent cells in salt-and-pepper fashion, indicating substantial functional differences within a presumed cell type. Intracellular recordings linked propensity to cell excitability. The stability of each cell’s propensity across conditions suggests this fundamental property has anatomical, transcriptional, and/or developmental origins.
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•Each CA1 pyramidal neuron has a propensity to have place fields that differs across cells•A cell’s propensity is fixed across contexts and time, scaled in rewarded and novel areas•The subpopulation of low propensity cells yields a sparse code for location•Intracellular data provide evidence that excitability underlies propensity differences
A unified response pattern of hippocampal place cells, driven by individual cell-intrinsic mechanisms, quantitatively predicts the structure of representation of space at the population level across varying conditions by the hippocampus in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the ...Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.
The origin of the spatial receptive fields of hippocampal place cells has not been established. A hippocampal CA1 pyramidal cell receives thousands of synaptic inputs, mostly from other spatially ...tuned neurons; however, how the postsynaptic neuron's cellular properties determine the response to these inputs during behavior is unknown. We discovered that, contrary to expectations from basic models of place cells and neuronal integration, a small, spatially uniform depolarization of the spatially untuned somatic membrane potential of a silent cell leads to the sudden and reversible emergence of a spatially tuned subthreshold response and place-field spiking. Such gating of inputs by postsynaptic neuronal excitability reveals a cellular mechanism for receptive field origin and may be critical for the formation of hippocampal memory representations.
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 Ca
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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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, ...and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision required to eventually converge on what this area does. Here we review early anatomical and electrophysiological results from cats and primates, as well as recent work in the rodent, identifying the connectivity, cell types, and physiological circuit mechanisms underlying the communication between the claustrum and the cortex. The emerging picture is one in which the rodent claustrum is closely tied to frontal limbic regions and plays a role in processes, such as attention, that are associated with these areas.
The claustrum is a small subcortical nucleus that has extensive excitatory connections with many cortical areas. While the anatomical connectivity from the claustrum to the cortex has been studied ...intensively, the physiological effect and underlying circuit mechanisms of claustrocortical communication remain elusive. Here we show that the claustrum provides strong, widespread, and long-lasting feedforward inhibition of the prefrontal cortex (PFC) sufficient to silence ongoing neural activity. This claustrocortical feedforward inhibition was predominantly mediated by interneurons containing neuropeptide Y, and to a lesser extent those containing parvalbumin. Therefore, in contrast to other long-range excitatory inputs to the PFC, the claustrocortical pathway is designed to provide overall inhibition of cortical activity. This unique circuit organization allows the claustrum to rapidly and powerfully suppress cortical networks and suggests a distinct role for the claustrum in regulating cognitive processes in prefrontal circuits.
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•The claustrum strongly inhibits, rather than excites, prefrontal cortex•Prefrontal NPY and PV interneurons are activated by the claustrum•Claustrocortical feedforward inhibition is predominantly mediated by NPY neurons
The claustrum provides a dense synaptic input to the cortex, but how claustrocortical projections modulate cortical activity is not known. Jackson et al. show that claustrocortical connections serve to inhibit cortical neural networks by activating specific subtypes of cortical interneurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The claustrum Smith, Jared B.; Lee, Albert K.; Jackson, Jesse
CB/Current biology,
12/2020, Volume:
30, Issue:
23
Journal Article
Peer reviewed
Open access
The claustrum is a brain region that has been investigated for over 200 years, yet its precise function remains unknown. In the final posthumously released article of Francis Crick, written with ...Christof Koch, the claustrum was suggested to be critically linked to consciousness. Though the claustrum remained relatively obscure throughout the last half century, it has enjoyed a renewed interest in the last 15 years since Crick and Koch’s article. During this time, the claustrum, like many other brain regions, has been studied with the myriad of modern systems neuroscience tools that have been made available by the intersection of genetic and viral technologies. This has uncovered new information about its anatomical connectivity and physiological properties and begun to reveal aspects of its function. From these studies, one clear consensus has emerged which supports Crick and Koch’s primary interest in the claustrum: the claustrum has widespread extensive connectivity with the entire cerebral cortex, suggesting a prominent role in ‘higher order processes’.
In this Primer, Smith et al. provide an overview of claustrum neurobiology, outlining its anatomical connectivity and potential role in attention and sleep states.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Daily experience suggests that we perceive distances near us linearly. However, the actual geometry of spatial representation in the brain is unknown. Here we report that neurons in the CA1 region of ...rat hippocampus that mediate spatial perception represent space according to a non-linear hyperbolic geometry. This geometry uses an exponential scale and yields greater positional information than a linear scale. We found that the size of the representation matches the optimal predictions for the number of CA1 neurons. The representations also dynamically expanded proportional to the logarithm of time that the animal spent exploring the environment, in correspondence with the maximal mutual information that can be received. The dynamic changes tracked even small variations due to changes in the running speed of the animal. These results demonstrate how neural circuits achieve efficient representations using dynamic hyperbolic geometry.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
To investigate the biological processes that are altered in obese subjects, we generated cell-specific integrated networks (INs) by merging genome-scale metabolic, transcriptional regulatory and ...protein-protein interaction networks. We performed genome-wide transcriptomics analysis to determine the global gene expression changes in the liver and three adipose tissues from obese subjects undergoing bariatric surgery and integrated these data into the cell-specific INs. We found dysregulations in mannose metabolism in obese subjects and validated our predictions by detecting mannose levels in the plasma of the lean and obese subjects. We observed significant correlations between plasma mannose levels, BMI, and insulin resistance (IR). We also measured plasma mannose levels of the subjects in two additional different cohorts and observed that an increased plasma mannose level was associated with IR and insulin secretion. We finally identified mannose as one of the best plasma metabolites in explaining the variance in obesity-independent IR.
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•We generated cell-specific integrated networks for lean and obese subjects•We found dysregulations in the mannose metabolism in obese subjects•Plasma mannose level was associated with insulin resistance independent of BMI•Mannose is used in explaining the variance in obesity-independent insulin resistance
Lee et al. merged genome-scale metabolic models (GEMs), transcriptional regulatory networks (TRNs), and protein-protein interaction networks (PPINs) to generate cell-specific integrated networks for hepatocytes, myocytes, and adipocytes of lean and obese subjects undergoing bariatric surgery. They identified, and independently validated, plasma mannose as highly associated with insulin resistance, independent of BMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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