Dendrites Of Neurons Research Articles

Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3

Apical and basal dendrites of pyramidal neurons receive anatomically and functionally distinct inputs, implying compartment-level functional diversity during behavior. To test this, we imaged in vivo calcium signals from soma, apical dendrites, and basal dendrites in mouse hippocampal CA3 pyramidal neurons during head-fixed navigation. To capture compartment-specific population dynamics, we developed computational tools to automatically segment dendrites and extract accurate fluorescence traces from densely labeled neurons. We validated the method on sparsely labeled preparations and synthetic data, predicting an optimal labeling density for high experimental throughput and analytical accuracy. Our method detected rapid, local dendritic activity. Dendrites showed robust spatial tuning, similar to soma but with higher activity rates. Across days, apical dendrites remained more stable and outperformed in decoding of the animal’s position. Thus, population-level apical and basal dendritic differences may reflect distinct compartment-specific input-output functions and computations in CA3. These tools will facilitate future studies mapping sub-cellular activity and their relation to behavior.

Multiple regulators constrain the abundance of C. elegans DLK-1 in ciliated sensory neurons.

The conserved MAP3K DLKs are widely known for their functions in synapse formation, axonal regeneration and degeneration, and neuronal survival, notably under traumatic injury and chronic disease conditions. In contrast, their roles in other neuronal compartments are much less explored. Through an unbiased forward genetic screening in C. elegans for altered patterns of GFP-tagged DLK-1 expressed from the endogenous locus, we have recently uncovered a mechanism by which the abundance of DLK-1 is tightly regulated by intraflagellar transport in ciliated sensory neurons. Here, we report additional mutants identified from the genetic screen. Most mutants exhibit increased accumulation of GFP::DLK-1 in sensory endings, and the levels of misaccumulated GFP::DLK-1 are exacerbated by loss of function in cebp-1, the b-Zip transcription factor acting downstream of DLK-1. We identify several new mutations in genes encoding proteins functioning in intraflagellar transport and cilia assembly, in components of BBSome, MAPK-15 and DYF-5 kinases. We report a novel mutation in the chaperone HSP90 that causes misaccumulation of GFP::DLK-1 and up-regulation of CEBP-1 selectively in ciliated sensory neurons. We also find that the guanylate cyclase ODR-1 constrains GFP::DLK-1 abundance throughout cilia and dendrites of AWC neurons. Moreover, in odr-1 mutants, AWC cilia display distorted morphology, which is ameliorated by loss of function in dlk-1 or cebp-1. These data expand the landscape of DLK-1 signaling in ciliated sensory neurons and underscore a high degree of cell- and neurite- specific regulation.

Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites.

Certain cognitive processes require inhibition provided by the somatostatin (SST) class of gamma-aminobutyric acid (GABA) neurons in the dorsolateral prefrontal cortex (DLPFC). This inhibition onto pyramidal neuron dendrites depends on both SST and GABA signaling. Although SST mRNA levels are lower in the DLPFC in schizophrenia, it is not known if SST neurons exhibit alterations in the capacity to synthesize GABA, principally via the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67). GAD67 and SST mRNA levels were quantified in individual SST neurons using fluorescence in situ hybridization in DLPFC layers 2-superficial 3, where SST neurons are enriched, in schizophrenia (n=46) and unaffected comparison (n=46) individuals. Findings were compared to GAD67 and SST mRNA levels quantified by polymerase chain reaction and to final educational attainment, a proxy measure for cognitive functioning. GAD67 (F1,84=13.1, p=0.0005, Cohen's d = -0.78) and SST (F1,84=10.1, p=0.002, Cohen's d = -0.64) mRNA levels in SST neurons were lower in schizophrenia, with no group differences in the relative density of SST neurons (F1,84=0.21, p=0.65). A presynaptic index of dendritic inhibition, derived by summing the alterations in GAD67 and SST mRNAs, was lower in 80.4% of individuals with schizophrenia and was associated with final educational attainment (adjusted odds ratio=1.44, p=0.022). Deficits in both GAD67 and SST mRNAs within SST neurons indicate that these neurons have a markedly reduced ability to inhibit postsynaptic pyramidal neuron dendrites in schizophrenia. These alterations likely contribute to cognitive dysfunction in schizophrenia.

Long-range inputome of prefrontal GABAergic interneurons in the Alzheimer's disease mouse.

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by damage to cortical circuits. However, the mechanisms underlying AD-associated changes in long-range circuits remain poorly understood. In this study, we used viral tracing and fluorescence micro-optical sectioning tomography (fMOST) imaging to investigate whole-brain changes in the input circuit of the frontal cortex of 5×FAD mice. Pathological axonal degeneration was widely observed in upstream regions, including the cortex, hippocampus, and thalamus, across all AD brains examined. The proportion of input neurons projecting to parvalbumin-expressing neurons, compared to those projecting to somatostatin-expressing neurons, decreased in the hippocampus and basal forebrain. This decline was closely related to mouse age and the cell type of the presynaptic input neurons. This study demonstrates the selective vulnerability of long-range circuits in the prelimbic area in AD at the mesoscopic level, thereby enhancing our understanding of circuit architecture degeneration across the brain. We used whole-brain imaging with single-cell resolution to generate brain-wide input maps of the Alzheimer's disease mouse model. The pathological changes in the input proportions showed relevance with the mouse age, distribution, and cell type of the presynaptic input neurons. Compared to the cell body and dendrites of the medial prefrontal cortex input neurons, the pathological changes in the axonal structure are more extensive.

A Neuron-Like Cellular Model for Severe Tinnitus Associated with Rare Variations in the ANK2 Gene.

Tinnitus is the perception of sound without an external source, often associated with changes in the auditory pathway and different brain regions. Recent research revealed an overload of missense variants in the ANK2 gene in individuals with severe tinnitus. ANK2, encoding ankyrin-B, regulates axon branching and inhibits microtubule invasion. Missense mutations in ANK2 may promote excessive axonal branching and the formation of excitatory synapses. This study aims to generate a patient-derived iPSC model from an individual with severe tinnitus and to differentiate these cells into otic-neural progenitors and inner ear neurons. We successfully generated a severe tinnitus cellular model through cell reprogramming. Using a two-stage neural differentiation protocol, we differentiated these cells into otic-neural progenitors and neuron-like cells. We confirmed the expression of genes, proteins, and cellular markers, including ANK2, otic-neural progenitors, and neuron-like cells through qPCR and immunostaining. Our analysis revealed higher ANK2 expression in the control cell line compared to the patient cell line. Although both lines formed multipolar neurons, the patient cell line displayed a unique pattern of closely grouped neurons with increased neuronal projections and dendrites compared to the control. This cellular model provides a valuable tool for studying the cellular and molecular changes associated with the ANK2 gene. It holds great promise for the development of novel drug and gene-based therapies for severe tinnitus.

Molecular switch of the dendrite-to-spine transport of TDP-43/FMRP-bound neuronal mRNAs and its impairment in ASD

BackgroundRegulation of messenger RNA (mRNA) transport and translation in neurons is essential for dendritic plasticity and learning/memory development. The trafficking of mRNAs along the hippocampal neuron dendrites remains translationally silent until they are selectively transported into the spines upon glutamate-induced receptor activation. However, the molecular mechanism(s) behind the spine entry of dendritic mRNAs under metabotropic glutamate receptor (mGluR)-mediated neuroactivation and long-term depression (LTD) as well as the fate of these mRNAs inside the spines are still elusive.MethodDifferent molecular and imaging techniques, e.g., immunoprecipitation (IP), RNA-IP, Immunofluorescence (IF)/fluorescence in situ hybridization (FISH), live cell imaging, live cell tracking of RNA using beacon, and mouse model study are used to elucidate a novel mechanism regulating dendritic spine transport of mRNAs in mammalian neurons.ResultsWe demonstrate here that brief mGluR1 activation-mediated dephosphorylation of pFMRP (S499) results in the dissociation of FMRP from TDP-43 and handover of TDP-43/Rac1 mRNA complex from the dendritic transport track on microtubules to myosin V track on the spine actin filaments. Rac1 mRNA thus enters the spines for translational reactivation and increases the mature spine density. In contrast, during mGluR1-mediated neuronal LTD, FMRP (S499) remains phosphorylated and the TDP-43/Rac1 mRNA complex, being associated with kinesin 1-FMRP/cortactin/drebrin, enters the spines owing to Ca2+-dependent microtubule invasion into spines, but without translational reactivation. In a VPA-ASD mouse model, this regulation become anomalous.ConclusionsThis study, for the first time, highlights the importance of posttranslational modification of RBPs, such as the neurodevelopmental disease-related protein FMRP, as the molecular switch regulating the dendrite-to-spine transport of specific mRNAs under mGluR1-mediated neurotransmissions. The misregulation of this switch could contribute to the pathogenesis of FMRP-related neurodisorders including the autism spectrum disorder (ASD). It also could indicate a molecular connection between ASD and neurodegenerative disease-related protein TDP-43 and opens up a new perspective of research to elucidate TDP-43 proteinopathy among patients with ASD.

Neuronal Imaging at 8-Bit Depth to Combine High Spatial and High Temporal Resolution With Acquisition Rates Up To 40 kHz.

A challenge in neuroimaging is acquiring frame sequences at high temporal resolution from the largest possible number of pixels. Measuring 1%-10% fluorescence changes normally requires 12-bit or higher bit depth, constraining the frame size allowing imaging in the kHz range. We resolved Ca2+ or membrane potential signals from cell populations or single neurons in brain slices by acquiring fluorescence at 8-bit depth and by binning pixels offline, achieving unprecedented frame sizes at kHz rates. In hippocampal slices stained with the Ca2+ indicator Fluo-4 AM, we resolved transients at 2 kHz from large frames. Along the apical dendrite of a layer-5 pyramidal neuron, we measured Ca2+ signals associated with a back-propagating action potential at 10 kHz. Finally, in the axon initial segment of the same cell type, we recorded an action potential at 40 kHz by voltage-sensitive dye imaging. This approach unlocks the potential for a range of imaging measurements.

Fetal growth restriction adversely impacts trajectory of hippocampal neurodevelopment and function.

The last pregnancy trimester is critical for fetal brain development but is a vulnerable period if the pregnancy is compromised by fetal growth restriction (FGR). The impact of FGR on the maturational development of neuronal morphology is not known, however, studies in fetal sheep allow longitudinal analysis in a long gestation species. Here we compared hippocampal neuron dendritogenesis in FGR and control fetal sheep at three timepoints equivalent to the third trimester of pregnancy, complemented by magnetic resonance image for brain volume, and electrophysiology for synaptic function. We hypothesized that the trajectory of hippocampal neuronal dendrite outgrowth would be decreased in the growth-restricted fetus, with implications for hippocampal volume, connectivity, and function. In control animals, total dendrite length increased with advancing gestation, but not in FGR, resulting in a significantly reduced trajectory of dendrite outgrowth in FGR fetuses for total length, branching, and complexity. Ex vivo electrophysiology analysis shows that paired-pulse facilitation was reduced in FGR compared to controls for cornu ammonis 1 hippocampal outputs, reflecting synaptic dysfunction. Hippocampal brain-derived neurotrophic factor density decreased over late gestation in FGR fetuses but not in controls. This study reveals that FGR is associated with a significant deviation in the trajectory of dendrite outgrowth of hippocampal neurons. Where dendrite length significantly increased over the third trimester of pregnancy in control brains, there was no corresponding increase over time in FGR brains, and the trajectory of dendrite outgrowth in FGR offspring was significantly reduced compared to controls. Reduced hippocampal dendritogenesis in FGR offspring has severe implications for the development of hippocampal connectivity and long-term function.

Distribution of spine classes shows intra-neuronal dendritic heterogeneity in mouse cortex.

Neuronal dendritic spines are central elements for memory and learning. Their morphology correlates with synaptic strength and is a proxy for function. Classic light microscopy cannot resolve spine morphology well, and techniques with higher resolution (electron microscopy and super-resolution light microscopy) typically do not provide spine data in large fields of view, e.g., along entire dendrites. Therefore, it remains unclear if spine types are organized on mesoscopic scales, despite their undisputed importance for understanding the brain. Recently, it was shown that the distribution of spine type is dendrite-specific in the turtle cortex, suggesting a mesoscopic organization, but leaving the question open if such a dendrite specificity also exists in mammals. Here, we determine if such a difference in spine-type distribution among dendrites also exists in the mouse brain. We used super-resolution stimulated emission depletion microscopy of complete dendrites and advanced morphological analysis in three dimensions to decipher morphological differences of spines on different dendrites. We found that spines of different shapes decorate different dendrites of the same neuron to a varying extent. Significant differences among the dendrites are apparent, based on spine classes as well as based on quantitative descriptors, such as spine length or head size. Our findings may indicate that it is an evolutionarily conserved principle that individual dendrites have distinct distributions of spine types hinting at individual roles.

Learning Dendritic-Neuron-Based Motion Detection for RGB Images: A Biomimetic Approach.

In this study, we designed a biomimetic artificial visual system (AVS) inspired by biological visual system that can process RGB images. Our approach begins by mimicking the photoreceptor cone cells to simulate the initial input processing followed by a learnable dendritic neuron model to replicate ganglion cells that integrate outputs from bipolar and horizontal cell simulations. To handle multi-channel integration, we utilize a nonlearnable dendritic neuron model to simulate the lateral geniculate nucleus (LGN), which consolidates outputs across color channels, an essential function in biological multi-channel processing. Cross-validation experiments show that AVS demonstrates strong generalization across varied object-background configurations, achieving accuracy where traditional models like EfN-B0, ResNet50, and ConvNeXt typically fall short. Additionally, our results across different training-to-testing data ratios reveal that AVS maintains over 96% test accuracy even with limited training data, underscoring its robustness in low-data scenarios. This demonstrates the practical advantage of the AVS model in applications where large-scale annotated datasets are unavailable or expensive to curate. This AVS model not only advances biologically inspired multi-channel processing but also provides a practical framework for efficient, integrated visual processing in computational models.

Neuropeptides: The Evergreen Jack-of-All-Trades in Neuronal Circuit Development and Regulation.

Neuropeptides are key modulators of adult neurocircuits, balancing their sensitivity to both excitation and inhibition, and fine-tuning fast neurotransmitter action under physiological conditions. Here, we reason that transient increases in neuropeptide availability and action exist during brain development for synapse maturation, selection, and maintenance. We discuss fundamental concepts of neuropeptide signaling at G protein-coupled receptors (GPCRs), with a particular focus on how signaling at neuropeptide GPCRs could underpin neuronal morphogenesis. We use galanin, a 29/30 amino acid-long neuropeptide, as an example for its retrograde release from the dendrites of thalamic neurons to impact the selection and wiring of sensory afferents originating at the trigeminal nucleus through galanin receptor 1 (GalR1) engagement. Thus, we suggest novel roles for neuropeptides, expressed transiently or permanently during both pre- and postnatal neuronal circuit development, with potentially life-long effects on circuit layout and ensuing behavioral operations.

A neuronal least-action principle for real-time learning in cortical circuits.

One of the most fundamental laws of physics is the principle of least action. Motivated by its predictive power, we introduce a neuronal least-action principle for cortical processing of sensory streams to produce appropriate behavioral outputs in real time. The principle postulates that the voltage dynamics of cortical pyramidal neurons prospectively minimizes the local somato-dendritic mismatch error within individual neurons. For output neurons, the principle implies minimizing an instantaneous behavioral error. For deep network neurons, it implies the prospective firing to overcome integration delays and correct for possible output errors right in time. The neuron-specific errors are extracted in the apical dendrites of pyramidal neurons through a cortical microcircuit that tries to explain away the feedback from the periphery, and correct the trajectory on the fly. Any motor output is in a moving equilibrium with the sensory input and the motor feedback during the ongoing sensory-motor transform. Online synaptic plasticity reduces the somatodendritic mismatch error within each cortical neuron and performs gradient descent on the output cost at any moment in time. The neuronal least-action principle offers an axiomatic framework to derive local neuronal and synaptic laws for global real-time computation and learning in the brain.

The Diagnostic Value of Cerebrospinal Fluid Neurogranin in Neurodegenerative Diseases.

Synaptic pathology is crucial in neurodegenerative diseases (NDs), and numerous studies show a correlation between synaptic proteins and the rate of cognitive decline in Alzheimer's disease, Parkinson's disease, dementia, and Creutzfeldt-Jacob's disease. Due to the fact that altered synaptic function is considered a core feature of the pathophysiology of neurodegenerative disorders, synaptic proteins, such as neurogranin, may serve as a biomarker of these diseases. Neurogranin is a postsynaptic protein located in the cell bodies and dendrites of neurons, foremost in the cerebral cortex, hippocampus, and striatum. It has been established that neurogranin is involved in synaptic plasticity and long-term potentiation. Literature data indicate that cerebrospinal fluid neurogranin may be useful as a biomarker for more accurate diagnosis and prognosis of neurodegenerative diseases. In this review, the diagnostic value of cerebrospinal fluid neurogranin in most common neurodegenerative diseases is examined.

Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites.

Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca2+ channels and ER Ca2+-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca2+ homeostasis, and local activation of the Ca2+/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca2+ modulatory machinery, facilitating signal transmission and ryanodine-receptor-dependent Ca2+ release at ER-PM junctions over 20μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca2+ release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.

Effects of dendritic Ca2+ spike on the modulation of spike timing with transcranial direct current stimulation in cortical pyramidal neurons.

Transcranial direct current stimulation (tDCS) generates a weak electric field (EF) within the brain, which induces opposite polarization in the soma and distal dendrite of cortical pyramidal neurons. The somatic polarization directly affects the spike timing, and dendritic polarization modulates the synaptically evoked dendritic activities. Ca2+ spike, the most dramatic dendritic activity, is crucial for synaptic integration and top-down signal transmission, thereby indirectly influencing the output spikes of pyramidal cells. Nevertheless, the role of dendritic Ca2+ spike in the modulation of neural spike timing with tDCS remains largely unclear. In this study, we use morphologically and biophysically realistic models of layer 5 pyramidal cells (L5 PCs) to simulate the dendritic Ca2+ spike and somatic Na+ spike in response to distal dendritic synaptic inputs under weak EF stimulation. Our results show that weak EFs modulate the spike timing through the modulation of dendritic Ca2+ spike and somatic polarization, and such field effects are dependent on synaptic inputs. At weak synaptic inputs, the spike timing is advanced due to the facilitation of dendritic Ca2+ spike by field-induced dendritic depolarization. Conversely, it is delayed by field-induceddendritic hyperpolarization. In this context, the Ca2+ spike exhibits heightened sensitivity to weak EFs, thereby governing the changes in spike timing. At strong synaptic inputs, somatic polarization dominates the changes in spike timing due to the decreased sensitivity of Ca2+ spike to EFs. Consequently, the spike timing is advanced/delayed by field-induced somatic depolarization/hyperpolarization. Moreover, EFs have significant effects on the changes in the timing of somatic spike and Ca2+ spike when synaptic current injection coincides with the onset of EFs. Field effects on spike timing follow a cosine dependency on the field polar angle, with maximum effects in the field direction parallel to the somato-dendritic axis. Furthermore, our results are robust to morphological and biological diversity. These findings clarify the modulation of spike timing with weak EFs and highlight the crucial role of dendritic Ca2+ spike. These predictions shed light on the neural basis of tDCS and should be considered when understanding the effect of tDCS on population dynamics and cognitive behavior.

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex.

Here we describe a type of depolarising plateau potentials (PPs; sustained depolarisations outlasting the stimuli) in layer 2/3 pyramidal cells (L2/3PC) in rat prefrontal cortex (PFC) slices, using whole-cell somatic recordings. To our knowledge, this PP type has not been described before. In particular, unlike previously described plateau potentials that originate in the large apical dendrite of L5 cortical pyramidal neurons, these L2/3PC PPs are generated independently of the apical dendrite. Thus, surprisingly, these PPs persisted when the apical dendrite was cut off (~50 μm from the soma), and were sustained by local calcium application only to the somatic and basal dendritic compartments. The prefrontal L2/3PCs have been postulated to have a key role in consciousness, according to the Global Neuronal Workspace Theory: their long-range cortico-cortical connections provide the architecture required for the "global work-space", "ignition", amplification, and sustained, reverberant activity, considered essential for conscious access. The PPs in L2/3PCs caused sustained spiking that profoundly altered the input-output relationships of these neurons, resembling the sustained activity suggested to underlie working memory and the mechanism underlying "behavioural time scale synaptic plasticity" in hippocampal pyramidal cells. The non-apical L2/3 PPs depended on metabotropic cholinergic (mAChR) or glutamatergic (mGluR) modulation, which is probably essential also for conscious brain states and experience, in both wakefulness and dreaming. Pharmacological tests indicated that the non-apical L2/3 PPs depend on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and require external calcium (Ca2+) and internal Ca2+ stores, but not voltage-gated Ca2+ channels, unlike Ca2+-dependent PPs in other cortical pyramidal neurons. These L2/3 non-apical plateau potentials may be involved in prefrontal functions, such as access consciousness, working memory, and executive functions such as planning, decision-making, and outcome prediction.

Ultrastructural Analysis Reveals Mitochondrial Placement Independent of Synapse Placement in Fine Caliber C. elegans Neurons.

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of metabolite diffusion over long distances, it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity such as synapses. Ultrastructural data over substantial portions of a neuron's extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis elegans' electron micrographs of John White and Sydney Brenner and found systematic differences in average mitochondrial length (ranging from 1.3 to 2.4 µm), diameter (0.18-0.24 µm) and volume density (3.7%-6.5%) between neurons of different function and neurotransmitter type, but found limited differences in mitochondrial length, diameter, and density between axons and dendrites of the same neurons. In analyses of mitochondrial distribution, mitochondria were found to be distributed randomly with respect to presynaptic sites. Presynaptic sites were primarily localized to varicosities, but mitochondria were no more likely to be found in synaptic varicosities than non-synaptic varicosities. Consistently, mitochondrial volume density was no greater in synaptic varicosities than non-synaptic varicosities. Therefore, beyond the capacity to disperse mitochondria throughout their length, at least in C. elegans, fine caliber neurons manifest limited subcellular control of mitochondrial size and distribution.

Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation.

The endoplasmic reticulum (ER) is a continuous cellular endomembrane network that displays focal specializations. Most notable examples of such specializations include the spine apparatus of neuronal dendrites and the cisternal organelle of axonal initial segments. Both organelles exhibit stacks of smooth ER sheets with a narrow lumen, interconnected by a dense protein matrix. The actin-binding protein synaptopodin is required for their formation, but the underlying mechanisms remain unknown. Here, we report that the spine apparatus and synaptopodin are conserved from flies to mammals and that a highly conserved region of this protein is necessary, but not sufficient, for its association with ER. We reveal a dual role of synaptopodin in generating actin bundles and in linking them to the ER. Expression of a synaptopodin construct constitutively anchored to the ER in non-neuronal cells is sufficient to generate stacked ER cisterns resembling the spine apparatus. Cisterns within these stacks are molecularly distinct from thesurrounding ER and are connected to each other by an actin-based matrix that contains proteins also found at the spine apparatus of neuronal spines. Our findings shed light on mechanisms governing the biogenesis of this peculiar structure and represent a step toward understanding the elusive properties of this organelle.

Amygdalar Excitation of Hippocampal Interneurons Can Lead to Emotion-driven Overgeneralization of Context.

Context is central to cognition: Detailed contextual representations enable flexible adjustment of behavior via comparison of the current situation with prior experience. Emotional experiences can greatly enhance contextual memory. However, sufficiently intense emotional signals can have the opposite effect, leading to weaker or less specific memories. How can emotional signals have such intensity-dependent effects? A plausible mechanistic account has emerged from recent anatomical data on the impact of the amygdala on the hippocampus in primates. In hippocampal CA3, the amygdala formed potent synapses on pyramidal neurons, calretinin (CR) interneurons, as well as parvalbumin (PV) interneurons. CR interneurons are known to disinhibit pyramidal neuron dendrites, whereas PV neurons provide strong perisomatic inhibition. This potentially counterintuitive connectivity, enabling amygdala to both enhance and inhibit CA3 activity, may provide a mechanism that can boost or suppress memory in an intensity-dependent way. To investigate this possibility, we simulated this connectivity pattern in a spiking network model. Our simulations revealed that moderate amygdala input can enrich CA3 representations of context through disinhibition via CR interneurons, but strong amygdalar input can impoverish CA3 activity through simultaneous excitation and feedforward inhibition via PV interneurons. Our model revealed an elegant circuit mechanism that mediates an affective "inverted U" phenomenon: There is an optimal level of amygdalar input that enriches hippocampal context representations, but on either side of this zone, representations are impoverished. This circuit mechanism helps explain why excessive emotional arousal can disrupt contextual memory and lead to overgeneralization, as seen in severe anxiety and posttraumatic stress disorder.

Dilated dendritic learning of global–local feature representation for medical image segmentation

Medical image segmentation serves as an important tool in the treatment of various medical diseases. However, achieving precise and efficient segmentation remains challenging due to the intricate structures and variations. Although neural network methods based on U-shaped structures have shown impressive results, they often lack effective representation of global–local features, leading to insufficient extraction of multi-scale and contextual information in medical image segmentation tasks. To tackle these challenges, we propose a novel approach: a dilated dendritic module with deep supervision, namely 3DL-Net. It integrates the flexible dilated convolution mechanism into the segmentation architecture, aiming to expand the model’s receptive field and capture richer global features. Additionally, in contrast to other segmentation architectures, we innovatively introduce the processing of local feature of shallow structures through the dendritic neuron module in medical images into 3DL-Net. This is the first time dendritic learning has been employed at the channel level and represents a pioneering approach to the local feature process. During the training process, 3DL-Net incorporates a deep supervision mechanism that utilizes our designed loss function. Due to the intermediate supervision signals at various network stages, providing feedback at multiple levels, the model refines its predictions across various scales, contributing to further enhanced segmentation outcomes. To evaluate the effectiveness of our proposed method, we conducted extensive experiments on three medical image datasets to demonstrate significant improvements in segmentation accuracy compared to state-of-the-art models. Our mDice metrics on three datasets achieved 86.61%, 87.87%, and 85.06%, surpassing the second-best models by 3.85%, 1.54%, and 0.95%.