Spatially structured inhibition defined by polarized parvalbumin interneuron axons promotes head direction tuning

In cortical microcircuits, it is generally assumed that fast-spiking parvalbumin interneurons mediate dense and nonselective inhibition. Some reports indicate sparse and structured inhibitory connectivity, but the computational relevance and the underlying spatial organization remain unresolved. In the rat superficial presubiculum, we find that inhibition by fast-spiking interneurons is organized in the form of a dominant super-reciprocal microcircuit motif where multiple pyramidal cells recurrently inhibit each other via a single interneuron. Multineuron recordings and subsequent 3D reconstructions and analysis further show that this nonrandom connectivity arises from an asymmetric, polarized morphology of fast-spiking interneuron axons, which individually cover different directions in the same volume. Network simulations assuming topographically organized input demonstrate that such polarized inhibition can improve head direction tuning of pyramidal cells in comparison to a “blanket of inhibition.” We propose that structured inhibition based on asymmetrical axons is an overarching spatial connectivity principle for tailored computation across brain regions.

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Anatomical organization of presubicular head-direction circuits

eLife ◽

10.7554/elife.14592 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 31

Author(s):

Patricia Preston-Ferrer ◽

Stefano Coletta ◽

Markus Frey ◽

Andrea Burgalossi

Keyword(s):

Pyramidal Neurons ◽

Pyramidal Cells ◽

Retrosplenial Cortex ◽

Theta Oscillations ◽

Head Direction ◽

Medial Entorhinal Cortex ◽

Directional Information ◽

Passive Rotation ◽

A Cell ◽

Fast Spiking

Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralateral PreS and retrosplenial cortex, respectively. Layer3 pyramidal neurons projected to the medial entorhinal cortex (MEC). By juxtacellularly recording PreS neurons in awake rats during passive-rotation, we found that head-direction responses were preferentially contributed by layer3 pyramidal cells, whose long-range axons branched within layer3 of the MEC. In contrast, layer2 neurons displayed distinct spike-shapes, were not modulated by head-direction but rhythmically-entrained by theta-oscillations. Fast-spiking interneurons showed only weak directionality and theta-rhythmicity, but were significantly modulated by angular velocity. Our data thus indicate that PreS neurons differentially contribute to head-direction coding, and point to a cell-type- and layer-specific routing of directional and non-directional information to downstream cortical targets.

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Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

Nature Communications ◽

10.1038/s41467-020-20328-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Lin Que ◽

David Lukacsovich ◽

Wenshu Luo ◽

Csaba Földy

Keyword(s):

Large Scale ◽

Cell Types ◽

Rna Seq ◽

Neuronal Identity ◽

Parvalbumin Interneurons ◽

Different Types ◽

Parvalbumin Interneuron ◽

Cam Profile ◽

Developmental Domains

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

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Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

Nature Communications ◽

10.1038/s41467-021-25035-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Cody L. Call ◽

Dwight E. Bergles

Keyword(s):

Cortical Neurons ◽

Regional Differences ◽

Brain Regions ◽

Axon Diameter ◽

Neuronal Identity ◽

Cortical Areas ◽

Myelin Sheaths ◽

Parvalbumin Interneurons ◽

Selection Of

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

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Comparison of age‐dependent alterations in thioredoxin 2 and thioredoxin reductase 2 expressions in hippocampi between mice and rats

Laboratory Animal Research ◽

10.1186/s42826-021-00088-y ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Yeon Ho Yoo ◽

Dae Won Kim ◽

Bai Hui Chen ◽

Hyejin Sim ◽

Bora Kim ◽

...

Keyword(s):

Thioredoxin Reductase ◽

Pyramidal Cells ◽

Brain Regions ◽

Young Age ◽

Cresyl Violet ◽

Western Blots ◽

Protein Levels ◽

Cresyl Violet Staining ◽

Age Dependent ◽

The Brain

Abstract Background Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. Results Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. Conclusions Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

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Suppression of Parvalbumin Interneuron Activity in the Prefrontal Cortex Recapitulates Features of Impaired Excitatory/Inhibitory Balance and Sensory Processing in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz123 ◽

2020 ◽

Vol 46 (4) ◽

pp. 981-989 ◽

Cited By ~ 3

Author(s):

Oana Toader ◽

Moritz von Heimendahl ◽

Niklas Schuelert ◽

Wiebke Nissen ◽

Holger Rosenbrock

Keyword(s):

Prefrontal Cortex ◽

Signal To Noise Ratio ◽

Treatment Options ◽

Brain Regions ◽

Inhibitory Interneuron ◽

Network Activity ◽

Limiting Factor ◽

Neuronal Populations ◽

Parvalbumin Interneuron ◽

New Treatment

Abstract Accumulating evidence supports parvalbumin expressing inhibitory interneuron (PV IN) dysfunction in the prefrontal cortex as a cause for cognitive impairment associated with schizophrenia (CIAS). PV IN decreased activity is suggested to be the culprit for many of the EEG deficits measured in patients, which correlate with deficits in working memory (WM), cognitive flexibility and attention. In the last few decades, CIAS has been recognized as a heavy burden on the quality of life of patients with schizophrenia, but little progress has been made in finding new treatment options. An important limiting factor in this process is the lack of adequate preclinical models and an incomplete understanding of the circuits engaged in cognition. In this study, we back-translated an auditory stimulation protocol regularly used in human EEG studies into mice and combined it with optogenetics to investigate the role of prefrontal cortex PV INs in excitatory/inhibitory balance and cortical processing. We also assessed spatial WM and reversal learning (RL) during inhibition of prefrontal cortex PV INs. We found significant impairments in trial-to-trial reliability, increased basal network activity and increased oscillation power at 20–60 Hz, and a decreased signal-to-noise ratio, but no significant impairments in behavior. These changes reflect some but not all neurophysiological deficits seen in patients with schizophrenia, suggesting that other neuronal populations and possibly brain regions are involved as well. Our work supports and expands previous findings and highlights the versatility of an approach that combines innovative technologies with back-translated tools used in humans.

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Oscillatory synchrony between head direction cells recorded bilaterally in the anterodorsal thalamic nuclei

Journal of Neurophysiology ◽

10.1152/jn.00881.2016 ◽

2017 ◽

Vol 117 (5) ◽

pp. 1847-1852 ◽

Cited By ~ 8

Author(s):

William N. Butler ◽

Jeffrey S. Taube

Keyword(s):

High Frequency ◽

Brain Regions ◽

High Frequency Oscillation ◽

Head Direction ◽

Thalamic Nuclei ◽

Head Direction Cells ◽

Oscillatory Pattern ◽

Cross Correlations ◽

Left And Right ◽

The Cross

The head direction (HD) circuit is a complex interconnected network of brain regions ranging from the brain stem to the cortex. Recent work found that HD cells corecorded ipsilaterally in the anterodorsal nucleus (ADN) of the thalamus displayed coordinated firing patterns. A high-frequency oscillation pattern (130–160 Hz) was visible in the cross-correlograms of these HD cell pairs. Spectral analysis further found that the power of this oscillation was greatest at 0 ms and decreased at greater lags, and demonstrated that there was greater synchrony between HD cells with similar preferred firing directions. Here, we demonstrate that the same high-frequency synchrony exists in HD cell pairs recorded contralaterally from one another in the bilateral ADN. When we examined the cross-correlograms of HD cells that were corecorded bilaterally, we observed the same high-frequency (~150- to 200-Hz) oscillatory relationship. The strength of this synchrony was similar to the synchrony seen in ipsilateral HD cell pairs, and the degree of synchrony in each cross-correlogram was dependent on the difference in tuning between the two cells. Additionally, the frequency rate of this oscillation appeared to be independent of the firing rates of the two cross-correlated cells. Taken together, these results imply that the left and right thalamic HD network are functionally related despite an absence of direct anatomical projections. However, anatomical tracing has found that each of the lateral mammillary nuclei (LMN) project bilaterally to both of the ADN, suggesting the LMN may be responsible for the functional connectivity observed between the two ADN. NEW & NOTEWORTHY This study used bilateral recording electrodes to examine whether head direction cells recorded simultaneously in both the left and right thalamus show coordinated firing. Cross-correlations of the cells’ spike trains revealed a high-frequency oscillatory pattern similar to that seen in cross-correlations between pairs of ipsilateral head direction cells, demonstrating that the bilateral thalamic head direction signals may be part of a single unified network.

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Cluster Analysis–Based Physiological Classification and Morphological Properties of Inhibitory Neurons in Layers 2–3 of Monkey Dorsolateral Prefrontal Cortex

Journal of Neurophysiology ◽

10.1152/jn.00156.2005 ◽

2005 ◽

Vol 94 (5) ◽

pp. 3009-3022 ◽

Cited By ~ 80

Author(s):

Leonid S. Krimer ◽

Aleksey V. Zaitsev ◽

Gabriela Czanner ◽

Sven Kröner ◽

Guillermo González-Burgos ◽

...

Keyword(s):

Cluster Analysis ◽

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Pyramidal Cells ◽

Inhibitory Neurons ◽

Morphological Properties ◽

Electrophysiological Properties ◽

Dorsolateral Prefrontal ◽

Fast Spiking ◽

Monkey Prefrontal Cortex

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2–3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.

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Multiple spatial codes for navigating 2-D semantic spaces

10.1101/2020.07.16.205955 ◽

2020 ◽

Author(s):

Simone Viganò ◽

Valerio Rubino ◽

Antonio Di Soccio ◽

Marco Buiatti ◽

Manuela Piazza

Keyword(s):

Physical Space ◽

Semantic Space ◽

Brain Regions ◽

Head Direction ◽

Word Meanings ◽

Neuronal Coding ◽

Coding Schemes ◽

Direction Of Movement ◽

Human Participants ◽

The Right

SummaryWhen mammals navigate in the physical environment, specific neurons such as grid-cells, head-direction cells, and place-cells activate to represent the navigable surface, the faced direction of movement, and the specific location the animal is visiting. Here we test the hypothesis that these codes are also activated when humans navigate abstract language-based representational spaces. Human participants learnt the meaning of novel words as arbitrary signs referring to specific artificial audiovisual objects varying in size and sound. Next, they were presented with sequences of words and asked to process them semantically while we recorded the activity of their brain using fMRI. Processing words in sequence was conceivable as movements in the semantic space, thus enabling us to systematically search for the different types of neuronal coding schemes known to represent space during navigation. By applying a combination of representational similarity and fMRI-adaptation analyses, we found evidence of i) a grid-like code in the right postero-medial entorhinal cortex, representing the general bidimensional layout of the novel semantic space; ii) a head-direction-like code in parietal cortex and striatum, representing the faced direction of movements between concepts; and iii) a place-like code in medial prefrontal, orbitofrontal, and mid cingulate cortices, representing the Euclidean distance between concepts. We also found evidence that the brain represents 1-dimensional distances between word meanings along individual sensory dimensions: implied size was encoded in secondary visual areas, and implied sound in Heschl’s gyrus/Insula. These results reveal that mentally navigating between 2D word meanings is supported by a network of brain regions hosting a variety of spatial codes, partially overlapping with those recruited for navigation in physical space.

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Homologous laminar organization of the mouse and human subiculum

10.1101/2019.12.20.883074 ◽

2019 ◽

Author(s):

Michael S. Bienkowski ◽

Farshid Sepehrband ◽

Nyoman D. Kurniawan ◽

Jim Stanis ◽

Laura Korobkova ◽

...

Keyword(s):

Gene Expression ◽

Hippocampal Formation ◽

Expression Patterns ◽

Pyramidal Cells ◽

Longitudinal Axis ◽

Brain Regions ◽

Brain Atlas ◽

Fiber Density ◽

Laminar Organization ◽

Hybridization Data

SummaryThe subiculum is the major output structure of the hippocampal formation and one of the brain regions most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.

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Uniquely excitable neurons enable precise and persistent information transmission through the retrosplenial cortex

10.1101/673954 ◽

2019 ◽

Author(s):

Ellen K.W. Brennan ◽

Shyam Kumar Sudhakar ◽

Izabela Jedrasiak-Cape ◽

Omar J. Ahmed

Keyword(s):

Input Resistance ◽

Retrosplenial Cortex ◽

Inhibitory Neurons ◽

Head Direction ◽

Cell Type ◽

Intrinsic Properties ◽

High Input ◽

Biophysical Models ◽

High Input Resistance ◽

Fast Spiking

ABSTRACTThe retrosplenial cortex (RSC) is essential for both memory and navigation, but the neural codes underlying these functions remain largely unknown. Here, we show that the most prominent cell type in layers 2/3 (L2/3) of the granular RSC is a uniquely excitable, small pyramidal cell. These cells have a low rheobase (LR), high input resistance, lack of spike-frequency adaptation, and spike widths intermediate to those of neighboring fast-spiking (FS) inhibitory neurons and regular-spiking (RS) excitatory neurons. LR cells are excitatory but rarely synapse onto neighboring neurons. Instead, L2/3 of RSC is an inhibition-dominated network with dense connectivity between FS cells and from FS to LR neurons. Biophysical models of LR but not RS cells precisely and continuously encode sustained input from afferent postsubicular head-direction cells. Thus, the unique intrinsic properties of LR neurons can support both the precision and persistence necessary to encode information over multiple timescales in the RSC.

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