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1.
PLoS Comput Biol ; 20(5): e1012110, 2024 May.
Article in English | MEDLINE | ID: mdl-38743789

ABSTRACT

Filopodia are thin synaptic protrusions that have been long known to play an important role in early development. Recently, they have been found to be more abundant in the adult cortex than previously thought, and more plastic than spines (button-shaped mature synapses). Inspired by these findings, we introduce a new model of synaptic plasticity that jointly describes learning of filopodia and spines. The model assumes that filopodia exhibit strongly competitive learning dynamics -similarly to additive spike-timing-dependent plasticity (STDP). At the same time it proposes that, if filopodia undergo sufficient potentiation, they consolidate into spines. Spines follow weakly competitive learning, classically associated with multiplicative, soft-bounded models of STDP. This makes spines more stable and sensitive to the fine structure of input correlations. We show that our learning rule has a selectivity comparable to additive STDP and captures input correlations as well as multiplicative models of STDP. We also show how it can protect previously formed memories and perform synaptic consolidation. Overall, our results can be seen as a phenomenological description of how filopodia and spines could cooperate to overcome the individual difficulties faced by strong and weak competition mechanisms.


Subject(s)
Dendritic Spines , Learning , Models, Neurological , Neuronal Plasticity , Pseudopodia , Pseudopodia/physiology , Neuronal Plasticity/physiology , Dendritic Spines/physiology , Learning/physiology , Animals , Humans , Computational Biology , Synapses/physiology , Neurons/physiology , Action Potentials/physiology
2.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38745556

ABSTRACT

The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.


Subject(s)
Pyramidal Cells , Humans , Pyramidal Cells/physiology , Animals , Male , Female , Mice , Adult , Dendritic Spines/physiology , Dendritic Spines/ultrastructure , Temporal Lobe/cytology , Dendrites/physiology , Middle Aged , Axons/physiology , Species Specificity
3.
Sci Rep ; 14(1): 12252, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806649

ABSTRACT

Sex hormones affect structural and functional plasticity in the rodent hippocampus. However, hormone levels not only differ between males and females, but also fluctuate across the female estrous cycle. While sex- and cycle-dependent differences in dendritic spine density and morphology have been found in the rodent CA1 region, but not in the CA3 or the dentate gyrus, comparable structural data on CA2, i.e. the hippocampal region involved in social recognition memory, is so far lacking. In this study, we, therefore, used wildtype male and female mice in diestrus or proestrus to analyze spines on dendritic segments from identified CA2 neurons. In basal stratum oriens, we found no differences in spine density, but a significant shift towards larger spine head areas in male mice compared to females. Conversely, in apical stratum radiatum diestrus females had a significantly higher spine density, and females in either cycle stage had a significant shift towards larger spine head areas as compared to males, with diestrus females showing the larger shift. Our results provide further evidence for the sexual dimorphism of hippocampal area CA2, and underscore the importance of considering not only the sex, but also the stage of the estrous cycle when interpreting morphological data.


Subject(s)
CA2 Region, Hippocampal , Dendritic Spines , Estrous Cycle , Animals , Male , Female , Dendritic Spines/metabolism , Dendritic Spines/physiology , Mice , Estrous Cycle/physiology , CA2 Region, Hippocampal/physiology , CA2 Region, Hippocampal/metabolism , Sex Characteristics , Neurons/metabolism
4.
Zool Res ; 45(3): 535-550, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38747058

ABSTRACT

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number, morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites, restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety- and depression-like behaviors in mice. Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament (F-actin) organization. Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3 (Ser3). Inhibition of ROCK2 activity with belumosudil (KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders.


Subject(s)
Actin Cytoskeleton , Cadherins , Dendritic Spines , Protocadherins , rho-Associated Kinases , Animals , Mice , Actin Cytoskeleton/metabolism , Cadherins/metabolism , Cadherins/genetics , Dendritic Spines/metabolism , Dendritic Spines/physiology , Gene Expression Regulation , rho-Associated Kinases/metabolism , rho-Associated Kinases/genetics , Protocadherins/genetics , Protocadherins/metabolism
5.
J Neurosci Res ; 102(4): e25319, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629777

ABSTRACT

The central amygdaloid nucleus (CeA) has an ancient phylogenetic development and functions relevant for animal survival. Local cells receive intrinsic amygdaloidal information that codes emotional stimuli of fear, integrate them, and send cortical and subcortical output projections that prompt rapid visceral and social behavior responses. We aimed to describe the morphology of the neurons that compose the human CeA (N = 8 adult men). Cells within CeA coronal borders were identified using the thionine staining and were further analyzed using the "single-section" Golgi method followed by open-source software procedures for two-dimensional and three-dimensional image reconstructions. Our results evidenced varied neuronal cell body features, number and thickness of primary shafts, dendritic branching patterns, and density and shape of dendritic spines. Based on these criteria, we propose the existence of 12 morphologically different spiny neurons in the human CeA and discuss the variability in the dendritic architecture within cellular types, including likely interneurons. Some dendritic shafts were long and straight, displayed few collaterals, and had planar radiation within the coronal neuropil volume. Most of the sampled neurons showed a few to moderate density of small stubby/wide spines. Long spines (thin and mushroom) were observed occasionally. These novel data address the synaptic processing and plasticity in the human CeA. Our morphological description can be combined with further transcriptomic, immunohistochemical, and electrophysiological/connectional approaches. It serves also to investigate how neurons are altered in neurological and psychiatric disorders with hindered emotional perception, in anxiety, following atrophy in schizophrenia, and along different stages of Alzheimer's disease.


Subject(s)
Central Amygdaloid Nucleus , Male , Adult , Animals , Humans , Phylogeny , Dendritic Spines/physiology , Neurons/physiology , Interneurons
6.
Neural Comput ; 36(5): 781-802, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38658027

ABSTRACT

Variation in the strength of synapses can be quantified by measuring the anatomical properties of synapses. Quantifying precision of synaptic plasticity is fundamental to understanding information storage and retrieval in neural circuits. Synapses from the same axon onto the same dendrite have a common history of coactivation, making them ideal candidates for determining the precision of synaptic plasticity based on the similarity of their physical dimensions. Here, the precision and amount of information stored in synapse dimensions were quantified with Shannon information theory, expanding prior analysis that used signal detection theory (Bartol et al., 2015). The two methods were compared using dendritic spine head volumes in the middle of the stratum radiatum of hippocampal area CA1 as well-defined measures of synaptic strength. Information theory delineated the number of distinguishable synaptic strengths based on nonoverlapping bins of dendritic spine head volumes. Shannon entropy was applied to measure synaptic information storage capacity (SISC) and resulted in a lower bound of 4.1 bits and upper bound of 4.59 bits of information based on 24 distinguishable sizes. We further compared the distribution of distinguishable sizes and a uniform distribution using Kullback-Leibler divergence and discovered that there was a nearly uniform distribution of spine head volumes across the sizes, suggesting optimal use of the distinguishable values. Thus, SISC provides a new analytical measure that can be generalized to probe synaptic strengths and capacity for plasticity in different brain regions of different species and among animals raised in different conditions or during learning. How brain diseases and disorders affect the precision of synaptic plasticity can also be probed.


Subject(s)
Information Theory , Neuronal Plasticity , Synapses , Animals , Synapses/physiology , Neuronal Plasticity/physiology , Dendritic Spines/physiology , CA1 Region, Hippocampal/physiology , Models, Neurological , Information Storage and Retrieval , Male , Hippocampus/physiology , Rats
7.
Cell Rep ; 43(4): 113966, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38507408

ABSTRACT

Perceptual learning improves our ability to interpret sensory stimuli present in our environment through experience. Despite its importance, the underlying mechanisms that enable perceptual learning in our sensory cortices are still not fully understood. In this study, we used in vivo two-photon imaging to investigate the functional and structural changes induced by visual stimulation in the mouse primary visual cortex (V1). Our results demonstrate that repeated stimulation leads to a refinement of V1 circuitry by decreasing the number of responsive neurons while potentiating their response. At the synaptic level, we observe a reduction in the number of dendritic spines and an overall increase in spine AMPA receptor levels in the same subset of neurons. In addition, visual stimulation induces synaptic potentiation in neighboring spines within individual dendrites. These findings provide insights into the mechanisms of synaptic plasticity underlying information processing in the neocortex.


Subject(s)
Dendritic Spines , Neuronal Plasticity , Primary Visual Cortex , Animals , Neuronal Plasticity/physiology , Mice , Primary Visual Cortex/physiology , Dendritic Spines/metabolism , Dendritic Spines/physiology , Receptors, AMPA/metabolism , Photic Stimulation , Mice, Inbred C57BL , Synapses/physiology , Synapses/metabolism , Neurons/physiology , Neurons/metabolism , Visual Cortex/physiology
8.
Anat Sci Int ; 99(3): 254-267, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38448780

ABSTRACT

The hippocampal complex of birds is a narrow-curved strip of tissue that plays a crucial role in learning, memory, spatial navigation, and emotional and sexual behavior. This study was conducted to evaluate the effect of unpredictable chronic mild stress in multipolar neurons of 3-, 5-, 7-, and 9-week-old chick's hippocampal complex. This study revealed that chronic stress results in neuronal remodeling by causing alterations in dendritic field, axonal length, secondary branching, corrected spine number, and dendritic branching at 25, 50, 75, and 100 µm. Due to stress, the overall dendritic length was significantly retracted in 3-week-old chick, whereas no significant difference was observed in 5- and 7-week-old chick, but again it was significantly retracted in 9-week-old chick along with the axonal length. So, this study indicates that during initial days of stress exposure, the dendritic field shows retraction, but when the stress continues up to a certain level, the neurons undergo structural modifications so that chicks adapt and survive in stressful conditions. The repeated exposure to chronic stress for longer duration leads to the neuronal structural disruption by retraction in the dendritic length as well as axonal length. Another characteristic which leads to structural alterations is the dendritic spines which significantly decreased in all age groups of stressed chicks and eventually leads to less synaptic connections, disturbance in physiology, and neurology, which affects the learning, memory, and coping ability of an individual.


Subject(s)
Chickens , Hippocampus , Neuronal Plasticity , Stress, Psychological , Animals , Hippocampus/pathology , Hippocampus/cytology , Neuronal Plasticity/physiology , Neurons/physiology , Dendrites/physiology , Dendritic Spines/physiology , Axons/physiology
9.
Methods Mol Biol ; 2761: 57-66, 2024.
Article in English | MEDLINE | ID: mdl-38427229

ABSTRACT

The objective of this chapter is to provide an overview of the methods used to investigate the connectivity and structure of the nervous system. These methods allow neuronal cells to be categorized according to their location, shape, and connections to other cells. The Golgi-Cox staining gives a thorough picture of all significant neuronal structures found in the brain that may be distinguished from one another. The most significant characteristic is its three-dimensional integrity since all neuronal structures may be followed continuously from one part to the next. Successions of sections of the brain's neurons are seen with the Golgi stain. The Golgi method is used to serially segment chosen brain parts, and the resulting neurons are produced from those sections.


Subject(s)
Dendrites , Dendritic Spines , Dendritic Spines/physiology , Dendrites/physiology , Neurons/physiology , Temporal Lobe , Silver Staining , Hippocampus
10.
Histol Histopathol ; 39(4): 411-423, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37966087

ABSTRACT

The morphophysiology of the nervous system changes and adapts in response to external environmental inputs and the experiences of individuals throughout their lives. Other changes in the organisms internal environment can also contribute to nervous system restructuring in the form of plastic changes that underlie its capacity to adapt to emerging psychophysiological conditions. These adaptive processes lead to subtle modifications of the organisms internal homeostasis which is closely related with the activity of chemical messengers, such as neurotransmitters and hormones. Hormones reach the brain through the bloodstream, where they activate specific receptors through which certain biochemical, physiological, and morphological changes take place in numerous regions. Fetal development, infancy, puberty, and adulthood are all periods of substantial hormone-mediated brain remodeling in both males and females. Adulthood, specifically, is associated with a broad range of life events, including reproductive cycles in both sexes, and pregnancy and menopause in women. Events of this kind occur concomitantly with eventual modifications in behavioral performance and, especially, in cognitive abilities like learning and memory that underlie, at least in part, plastic changes in the dendritic spines of the neuronal cells in cerebral areas involved in processing cognitive information. Estrogens form a family that consists of three molecules [17ß-estradiol (E2), estrone, estriol] which are deeply involved in regulating numerous bodily functions in different stages of the life-cycle, including the modulation of cognitive performance. This review addresses the effects of E2 on the dendritic spine-mediated synaptic organization of cognitive performance throughout the life span.


Subject(s)
Dendritic Spines , Estradiol , Male , Humans , Female , Estradiol/pharmacology , Dendritic Spines/physiology , Longevity , Estrogens/pharmacology , Brain , Neuronal Plasticity/physiology
11.
Brain Struct Funct ; 229(1): 143-149, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37943311

ABSTRACT

Olfactory bulbectomy (OBX) is an experimental strategy that is widely employed because it produces changes at different levels (from behavioral to molecular) that can be related to symptoms of depression in humans. This procedure has been widely studied in adult rats, but little information has been obtained of its effect in neonatal rats. The objective of the present study was to evaluate learning and memory capacity and dendritic spine density in dorsal hippocampal CA3 neurons. Seven-day-old male and female Wistar rats were subjected to nOBX by suction, we included an intact group as a control (CON) and a sham-operated group (SHAM), too. Spatial learning and memory were measured at 56 days of age using a Morris water maze. A different cohort of experimental groups was used to measure dendritic spine density by Golgi-Cox impregnation. Male rats with nOBX showed a pronounced spatial learning deficit than female rats. Also, there was a significant decrease in basilar dendritic spine density in female rats with nOBX compared to the CON group. No changes were observed in this variable in male rats with nOBX. Our results allow us to suggest that there is sexual dimorphism in the effect of nOBX on the dorsal hippocampus and its relationship with spatial learning and memory processes.


Subject(s)
Dendritic Spines , Spatial Learning , Humans , Rats , Animals , Male , Female , Dendritic Spines/physiology , Rats, Wistar , Maze Learning/physiology , Hippocampus , Neurons
12.
Biotechniques ; 76(1): 37-42, 2024 01.
Article in English | MEDLINE | ID: mdl-37994419

ABSTRACT

We developed a simple yet powerful technique to visualize neuronal morphology in human brain tissues. By ballistically shooting DiI (1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate)-coated tungsten particles to randomly label neurons, then clearing tissues with OPTIClear, we demonstrated the tracing of branched dendritic trees and spines in three dimensions. High-resolution imaging revealed dendrites up to 300 µm long and spine necks down to 200 nm across. Quantitative analyses of 1304 dendritic spines showed no decrease in spine density with imaging depth, indicating excellent clearing and tracing. Segmentation and modeling of dendritic spines enabled morphological characterization. This technique enables assumption-free, high-resolution and cost-efficient visualization of neuronal morphology in human tissues. Combined with immunohistochemistry and electron microscopy, it could provide new perspectives for studying human neuroanatomy and pathology.


Subject(s)
Dendritic Spines , Imaging, Three-Dimensional , Humans , Dendritic Spines/physiology , Imaging, Three-Dimensional/methods , Neurons , Brain , Immunohistochemistry
13.
Neural Comput ; 36(2): 271-311, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38101326

ABSTRACT

We investigate a mutual relationship between information and energy during the early phase of LTP induction and maintenance in a large-scale system of mutually coupled dendritic spines, with discrete internal states and probabilistic dynamics, within the framework of nonequilibrium stochastic thermodynamics. In order to analyze this computationally intractable stochastic multidimensional system, we introduce a pair approximation, which allows us to reduce the spine dynamics into a lower-dimensional manageable system of closed equations. We found that the rates of information gain and energy attain their maximal values during an initial period of LTP (i.e., during stimulation), and after that, they recover to their baseline low values, as opposed to a memory trace that lasts much longer. This suggests that the learning phase is much more energy demanding than the memory phase. We show that positive correlations between neighboring spines increase both a duration of memory trace and energy cost during LTP, but the memory time per invested energy increases dramatically for very strong, positive synaptic cooperativity, suggesting a beneficial role of synaptic clustering on memory duration. In contrast, information gain after LTP is the largest for negative correlations, and energy efficiency of that information generally declines with increasing synaptic cooperativity. We also find that dendritic spines can use sparse representations for encoding long-term information, as both energetic and structural efficiencies of retained information and its lifetime exhibit maxima for low fractions of stimulated synapses during LTP. Moreover, we find that such efficiencies drop significantly with increasing the number of spines. In general, our stochastic thermodynamics approach provides a unifying framework for studying, from first principles, information encoding, and its energy cost during learning and memory in stochastic systems of interacting synapses.


Subject(s)
Dendritic Spines , Long-Term Potentiation , Long-Term Potentiation/physiology , Dendritic Spines/physiology , Synapses/physiology , Learning , Hippocampus/physiology
14.
Elife ; 122023 Dec 07.
Article in English | MEDLINE | ID: mdl-38059805

ABSTRACT

Postsynaptic mitochondria are critical for the development, plasticity, and maintenance of synaptic inputs. However, their relationship to synaptic structure and functional activity is unknown. We examined a correlative dataset from ferret visual cortex with in vivo two-photon calcium imaging of dendritic spines during visual stimulation and electron microscopy reconstructions of spine ultrastructure, investigating mitochondrial abundance near functionally and structurally characterized spines. Surprisingly, we found no correlation to structural measures of synaptic strength. Instead, we found that mitochondria are positioned near spines with orientation preferences that are dissimilar to the somatic preference. Additionally, we found that mitochondria are positioned near groups of spines with heterogeneous orientation preferences. For a subset of spines with a mitochondrion in the head or neck, synapses were larger and exhibited greater selectivity to visual stimuli than those without a mitochondrion. Our data suggest mitochondria are not necessarily positioned to support the energy needs of strong spines, but rather support the structurally and functionally diverse inputs innervating the basal dendrites of cortical neurons.


Subject(s)
Dendritic Spines , Ferrets , Animals , Dendritic Spines/physiology , Dendrites/physiology , Neurons/physiology , Synapses/physiology , Mitochondria
15.
Sci Rep ; 13(1): 22207, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097675

ABSTRACT

Many experiments suggest that long-term information associated with neuronal memory resides collectively in dendritic spines. However, spines can have a limited size due to metabolic and neuroanatomical constraints, which should effectively limit the amount of encoded information in excitatory synapses. This study investigates how much information can be stored in the population of sizes of dendritic spines, and whether it is optimal in any sense. It is shown here, using empirical data for several mammalian brains across different regions and physiological conditions, that dendritic spines nearly maximize entropy contained in their volumes and surface areas for a given mean size in cortical and hippocampal regions. Although both short- and heavy-tailed fitting distributions approach [Formula: see text] of maximal entropy in the majority of cases, the best maximization is obtained primarily for short-tailed gamma distribution. We find that most empirical ratios of standard deviation to mean for spine volumes and areas are in the range [Formula: see text], which is close to the theoretical optimal ratios coming from entropy maximization for gamma and lognormal distributions. On average, the highest entropy is contained in spine length ([Formula: see text] bits per spine), and the lowest in spine volume and area ([Formula: see text] bits), although the latter two are closer to optimality. In contrast, we find that entropy density (entropy per spine size) is always suboptimal. Our results suggest that spine sizes are almost as random as possible given the constraint on their size, and moreover the general principle of entropy maximization is applicable and potentially useful to information and memory storing in the population of cortical and hippocampal excitatory synapses, and to predicting their morphological properties.


Subject(s)
Dendritic Spines , Neurons , Animals , Dendritic Spines/physiology , Cerebral Cortex , Brain , Synapses/physiology , Hippocampus , Mammals
16.
Curr Opin Neurobiol ; 83: 102808, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37972535

ABSTRACT

If the genome defines the program for the operations of a cell, signaling networks execute it. These cascades of chemical, cell-biological, structural, and trafficking events span milliseconds (e.g., synaptic release) to potentially a lifetime (e.g., stabilization of dendritic spines). In principle almost every aspect of neuronal function, particularly at the synapse, depends on signaling. Thus dysfunction of these cascades, whether through mutations, local dysregulation, or infection, leads to disease. The sheer complexity of these pathways is matched by the range of diseases and the diversity of their phenotypes. In this review, we discuss how to build computational models, how these models are essential to tackle this complexity, and the benefits of using families of models at different levels of detail to understand signaling in health and disease.


Subject(s)
Dendritic Spines , Neuronal Plasticity , Dendritic Spines/physiology , Neuronal Plasticity/physiology , Signal Transduction , Neurons , Synapses/physiology
17.
Biophys J ; 122(22): 4303-4315, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37837192

ABSTRACT

Dendritic spines are small protrusions that mediate most of the excitatory synaptic transmission in the brain. Initially, the anatomical structure of spines has suggested that they serve as isolated biochemical and electrical compartments. Indeed, following ample experimental evidence, it is now widely accepted that a significant physiological role of spines is to provide biochemical compartmentalization in signal integration and plasticity in the nervous system. In contrast to the clear biochemical role of spines, their electrical role is uncertain and is currently being debated. This is mainly because spines are small and not accessible to conventional experimental methods of electrophysiology. Here, I focus on reviewing the literature on the electrical properties of spines, including the initial morphological and theoretical modeling studies, indirect experimental approaches based on measurements of diffusional resistance of the spine neck, indirect experimental methods using two-photon uncaging of glutamate on spine synapses, optical imaging of intracellular calcium concentration changes, and voltage imaging with organic and genetically encoded voltage-sensitive probes. The interpretation of evidence from different preparations obtained with different methods has yet to reach a consensus, with some analyses rejecting and others supporting an electrical role of spines in regulating synaptic signaling. Thus, there is a need for a critical comparison of the advantages and limitations of different methodological approaches. The only experimental study on electrical signaling monitored optically with adequate sensitivity and spatiotemporal resolution using voltage-sensitive dyes concluded that mushroom spines on basal dendrites of cortical pyramidal neurons in brain slices have no electrical role.


Subject(s)
Dendrites , Dendritic Spines , Dendritic Spines/physiology , Pyramidal Cells , Synaptic Transmission , Glutamic Acid , Synapses
18.
J Neurosci ; 43(41): 6833-6840, 2023 10 11.
Article in English | MEDLINE | ID: mdl-37821232

ABSTRACT

The loss of excitatory synapses is known to underlie the cognitive deficits in Alzheimer's disease (AD). Although much is known about the mechanisms underlying synaptic loss in AD, how neurons compensate for this loss and whether this provides cognitive benefits remain almost completely unexplored. In this review, we describe two potential compensatory mechanisms implemented following synaptic loss: the enlargement of the surviving neighboring synapses and the regeneration of synapses. Because dendritic spines, the postsynaptic site of excitatory synapses, are easily visualized using light microscopy, we focus on a range of microscopy approaches to monitor synaptic loss and compensation. Here, we stress the importance of longitudinal dendritic spine imaging, as opposed to fixed-tissue imaging, to gain insights into the temporal dynamics of dendritic spine compensation. We believe that understanding the molecular mechanisms behind these and other forms of synaptic compensation and regeneration will be critical for the development of therapeutics aiming at delaying the onset of cognitive deficits in AD.


Subject(s)
Alzheimer Disease , Cognition Disorders , Humans , Synapses , Neuronal Plasticity/physiology , Neurons , Dendritic Spines/physiology
19.
Proc Jpn Acad Ser B Phys Biol Sci ; 99(8): 254-305, 2023.
Article in English | MEDLINE | ID: mdl-37821392

ABSTRACT

Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical forces generated by excitatory synapses on dendritic spines to modulate presynaptic function. From in vivo and in vitro studies, we outline five central principles of synaptic mechanics in brain function: P1: Stability - Underpinning the integral relationship between the structure and function of the spine synapses. P2: Extrinsic dynamics - Highlighting synapse-selective structural plasticity which plays a crucial role in Hebbian associative learning, distinct from pathway-selective long-term potentiation (LTP) and depression (LTD). P3: Neuromodulation - Analyzing the role of G-protein-coupled receptors, particularly dopamine receptors, in time-sensitive modulation of associative learning frameworks such as Pavlovian classical conditioning and Thorndike's reinforcement learning (RL). P4: Instability - Addressing the intrinsic dynamics crucial to memory management during continual learning, spotlighting their role in "spine dysgenesis" associated with mental disorders. P5: Mechanics - Exploring how synaptic mechanics influence both sides of synapses to establish structural traces of short- and long-term memory, thereby aiding the integration of mental functions. We also delve into the historical background and foresee impending challenges.


Subject(s)
Dendritic Spines , Neuronal Plasticity , Humans , Neuronal Plasticity/physiology , Dendritic Spines/physiology , Long-Term Potentiation/physiology , Synapses , Cognition
20.
Curr Biol ; 33(16): 3465-3477.e5, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37543035

ABSTRACT

Regional brain activity often decreases from baseline levels in response to external events, but how neurons develop such negative responses is unclear. To study this, we leveraged the negative response that develops in the primary motor cortex (M1) after classical fear learning. We trained mice with a fear conditioning paradigm while imaging their brains with standard two-photon microscopy. This enabled monitoring changes in neuronal responses to the tone with synaptic resolution through learning. We found that M1 layer 5 pyramidal neurons (L5 PNs) developed negative tone responses within an hour after conditioning, which depended on the weakening of their dendritic spines that were active during training. Blocking this form of anti-Hebbian plasticity using an optogenetic manipulation of CaMKII activity disrupted negative tone responses and freezing. Therefore, reducing the strength of spines active at the time of memory encoding leads to negative responses of L5 PNs. In turn, these negative responses curb M1's capacity for promoting movement, thereby aiding freezing. Collectively, this work provides a mechanistic understanding of how area-specific negative responses to behaviorally relevant cues can be achieved.


Subject(s)
Motor Cortex , Mice , Animals , Dendritic Spines/physiology , Freezing , Pyramidal Cells/physiology , Learning/physiology , Neuronal Plasticity/physiology
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