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Current Research in Neurobiology 2024We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization,... (Review)
Review
We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology.
PubMed: 38665363
DOI: 10.1016/j.crneur.2024.100129 -
Cell Reports Nov 2023Identifying molecular specializations in cortical circuitry supporting complex behaviors, like learned vocalizations, requires understanding of the neuroanatomical...
Identifying molecular specializations in cortical circuitry supporting complex behaviors, like learned vocalizations, requires understanding of the neuroanatomical context from which these circuits arise. In songbirds, the robust arcopallial nucleus (RA) provides descending cortical projections for fine vocal-motor control. Using single-nuclei transcriptomics and spatial gene expression mapping in zebra finches, we have defined cell types and molecular specializations that distinguish RA from adjacent regions involved in non-vocal motor and sensory processing. We describe an RA-specific projection neuron, differential inhibitory subtypes, and glia specializations and have probed predicted GABAergic interneuron subtypes electrophysiologically within RA. Several cell-specific markers arise developmentally in a sex-dependent manner. Our interactive apps integrate cellular data with developmental and spatial distribution data from the gene expression brain atlas ZEBrA. Users can explore molecular specializations of vocal-motor neurons and support cells that likely reflect adaptations key to the physiology and evolution of vocal control circuits and refined motor skills.
Topics: Animals; Finches; Motor Cortex; Brain; Learning; Motor Neurons; Vocalization, Animal
PubMed: 37910500
DOI: 10.1016/j.celrep.2023.113344 -
Neuron Mar 2024In this issue of Neuron, Znamenskiy et al. unveil functional connection specificity between PV+ inhibitory interneurons and excitatory pyramidal neurons in mouse visual...
In this issue of Neuron, Znamenskiy et al. unveil functional connection specificity between PV+ inhibitory interneurons and excitatory pyramidal neurons in mouse visual cortex, providing a circuit mechanism for stable amplification of cortical subpopulations.
Topics: Mice; Animals; Neurons; Pyramidal Cells; Interneurons; Visual Cortex; Parvalbumins
PubMed: 38513616
DOI: 10.1016/j.neuron.2024.02.018 -
Cell Reports Sep 2023Visual stimuli that deviate from the current context elicit augmented responses in the primary visual cortex (V1). These heightened responses, known as "deviance...
Visual stimuli that deviate from the current context elicit augmented responses in the primary visual cortex (V1). These heightened responses, known as "deviance detection," require local inhibition in the V1 and top-down input from the anterior cingulate area (ACa). Here, we investigated the mechanisms by which the ACa and V1 interact to support deviance detection. Local field potential recordings in mice during an oddball paradigm showed that ACa-V1 synchrony peaks in the theta/alpha band (≈10 Hz). Two-photon imaging in the V1 revealed that mainly pyramidal neurons exhibited deviance detection, while contextually redundant stimuli increased vasoactive intestinal peptide (VIP)-positive interneuron (VIP) activity and decreased somatostatin-positive interneuron (SST) activity. Optogenetic drive of ACa-V1 inputs at 10 Hz activated V1-VIPs but inhibited V1-SSTs, mirroring the dynamics present during the oddball paradigm. Chemogenetic inhibition of V1-VIPs disrupted Aca-V1 synchrony and deviance detection in the V1. These results outline temporal and interneuron-specific mechanisms of top-down modulation that support visual context processing.
Topics: Animals; Mice; Visual Perception; Cerebral Cortex; Pyramidal Cells; Interneurons; Optogenetics; Vasoactive Intestinal Peptide
PubMed: 37708021
DOI: 10.1016/j.celrep.2023.113133 -
Cerebral Cortex (New York, N.Y. : 1991) Apr 2024The axons of neocortical pyramidal neurons are frequently myelinated. Heterogeneity in the topography of axonal myelination in the cerebral cortex has been attributed to...
The axons of neocortical pyramidal neurons are frequently myelinated. Heterogeneity in the topography of axonal myelination in the cerebral cortex has been attributed to a combination of electrophysiological activity, axonal morphology, and neuronal-glial interactions. Previously, we showed that axonal segment length and caliber are critical local determinants of fast-spiking interneuron myelination. However, the factors that determine the myelination of individual axonal segments along neocortical pyramidal neurons remain largely unexplored. Here, we used structured illumination microscopy to examine the extent to which axonal morphology is predictive of the topography of myelination along neocortical pyramidal neurons. We identified critical thresholds for axonal caliber and interbranch distance that are necessary, but not sufficient, for myelination of pyramidal cell axons in mouse primary somatosensory cortex (S1). Specifically, we found that pyramidal neuron axonal segments with a caliber < 0.24 μm or interbranch distance < 18.10 μm are rarely myelinated. Moreover, we further confirmed that these findings in mice are similar for human neocortical pyramidal cell myelination (caliber < 0.25 μm, interbranch distance < 19.00 μm), suggesting that this mechanism is evolutionarily conserved. Taken together, our findings suggest that axonal morphology is a critical correlate of the topography and cell-type specificity of neocortical myelination.
Topics: Humans; Animals; Mice; Pyramidal Cells; Neocortex; Axons; Myelin Sheath; Interneurons
PubMed: 38610088
DOI: 10.1093/cercor/bhae147 -
Folia Morphologica Oct 2023The brain is an important part of the mammalian nervous system, is highly sensitive to hypoxia, and plays an important role in the adaptation of the body to hypoxic...
The brain is an important part of the mammalian nervous system, is highly sensitive to hypoxia, and plays an important role in the adaptation of the body to hypoxic environments. This study was conducted to study the distribution and expression of hypoxia-related factors (hypoxia-inducible factor 1α, HIF-1α; erythropoietin, EPO; vascular endothelial growth factor, VEGF; vascular cell adhesion molecule, VCAM) in the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina in yaks of different ages (4d, 6-months-old and adult). Paraffin sections were obtained from the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina of healthy yak for 4-day-old, 6-months-old and adult yaks. Histological characteristics were assessed by haematoxylin staining. Immunohistochemical staining was performed to detect the distribution and expression of HIF-1α, EPO, VEGF and VCAM proteins. Immunohistochemical results showed that HIF-1α, EPO, VEGF, and VCAM were expressed in the pyramidal cell layer of the yak cerebrum, and distributed in the cerebellum granulose cell layer, Purkinje cell layer and medulla layer, and were mainly positive in Purkinje cells and medulla. It is expressed in the cell bodies of the medulla oblongata and the quadrimatous neurons. The expression level in the medulla oblongata was higher, indicating may play a crucial role in functional cohesion. The expression of HIF-1α in 4 d cerebellar tissues was higher than that in other age groups, and the expression of HIF-1α in the medulla oblongata increased with age. In addition, the expression levels of EPO and VEGF in the 6-month-old group were slightly higher than those in the other age groups. It is speculated that EPO and VEGF have obvious protective effects on brain tissue in the 6-month-old age group; VCAM showed no significant differences in the cerebrum, cerebellum, medulla oblongata, or corpora quadrigemina of the yaks. This study provides basic data for further exploration of the adaptive mechanism of plateau yak brain tissue.
PubMed: 37822067
DOI: 10.5603/fm.93596 -
Frontiers in Cellular Neuroscience 2023Presynaptic plasticity is an activity-dependent change in the neurotransmitter release and plays a key role in dynamic modulation of synaptic strength. Particularly,... (Review)
Review
Presynaptic plasticity is an activity-dependent change in the neurotransmitter release and plays a key role in dynamic modulation of synaptic strength. Particularly, presynaptic potentiation mediated by cyclic adenosine monophosphate (cAMP) is widely seen across the animals and thought to contribute to learning and memory. Hippocampal mossy fiber-CA3 pyramidal cell synapses have been used as a model because of robust presynaptic potentiation in short- and long-term forms. Moreover, direct presynaptic recordings from large mossy fiber terminals allow one to dissect the potentiation mechanisms. Recently, super-resolution microscopy and flash-and-freeze electron microscopy have revealed the localizations of release site molecules and synaptic vesicles during the potentiation at a nanoscale, identifying the molecular mechanisms of the potentiation. Incorporating these growing knowledges, we try to present plausible mechanisms underlying the cAMP-mediated presynaptic potentiation.
PubMed: 37519634
DOI: 10.3389/fncel.2023.1237589 -
Science Advances Feb 2024Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly...
Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly understood. Gamma oscillations (30 to 80 hertz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma power. Gamma potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit computational model of CA3 gamma oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma power and completely accounts for gamma potentiation. We reaffirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma potentiation requires PVI-specific signaling via a Gq/PKC pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma activity-dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.
Topics: Animals; Parvalbumins; Hippocampus; Long-Term Potentiation; Signal Transduction; Interneurons; Neuronal Plasticity
PubMed: 38295164
DOI: 10.1126/sciadv.adj7427 -
Neuroscience Bulletin Feb 2024As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely...
As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats. Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions: the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli, whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties. Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors. Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats, whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain. These results provide direct evidence for the representations of nociceptive information in vCA1.
Topics: Rats; Animals; CA1 Region, Hippocampal; Hyperalgesia; Nociception; Neural Pathways; Hippocampus; Pyramidal Cells; Neuralgia
PubMed: 37440103
DOI: 10.1007/s12264-023-01086-x -
Bioinformatics (Oxford, England) Oct 2023Recent rapid developments in spatial transcriptomic techniques at cellular resolution have gained increasing attention. However, the unique characteristics of...
MOTIVATION
Recent rapid developments in spatial transcriptomic techniques at cellular resolution have gained increasing attention. However, the unique characteristics of large-scale cellular resolution spatial transcriptomic datasets, such as the limited number of transcripts captured per spot and the vast number of spots, pose significant challenges to current cell-type deconvolution methods.
RESULTS
In this study, we introduce stVAE, a method based on the variational autoencoder framework to deconvolve the cell-type composition of cellular resolution spatial transcriptomic datasets. To assess the performance of stVAE, we apply it to five datasets across three different biological tissues. In the Stereo-seq and Slide-seqV2 datasets of the mouse brain, stVAE accurately reconstructs the laminar structure of the pyramidal cell layers in the cortex, which are mainly organized by the subtypes of telencephalon projecting excitatory neurons. In the Stereo-seq dataset of the E12.5 mouse embryo, stVAE resolves the complex spatial patterns of osteoblast subtypes, which are supported by their marker genes. In Stereo-seq and Pixel-seq datasets of the mouse olfactory bulb, stVAE accurately delineates the spatial distributions of known cell types. In summary, stVAE can accurately identify spatial patterns of cell types and their relative proportions across spots for cellular resolution spatial transcriptomic data. It is instrumental in understanding the heterogeneity of cell populations and their interactions within tissues.
AVAILABILITY AND IMPLEMENTATION
stVAE is available in GitHub (https://github.com/lichen2018/stVAE) and Figshare (https://figshare.com/articles/software/stVAE/23254538).
Topics: Animals; Mice; Transcriptome; Algorithms; Software; Sequence Analysis, RNA; Single-Cell Analysis; Gene Expression Profiling
PubMed: 37862237
DOI: 10.1093/bioinformatics/btad642