RESUMEN
Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1-4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Asunto(s)
Potenciación a Largo Plazo , Depresión Sináptica a Largo Plazo , Plasticidad Neuronal , Sinapsis , Animales , Espinas Dendríticas/fisiología , Potenciación a Largo Plazo/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Modelos Neurológicos , Plasticidad Neuronal/fisiología , Sinapsis/fisiologíaRESUMEN
Producing dense 3D reconstructions from biological imaging data is a challenging instance segmentation task that requires significant ground-truth training data for effective and accurate deep learning-based models. Generating training data requires intense human effort to annotate each instance of an object across serial section images. Our focus is on the especially complicated brain neuropil, comprising an extensive interdigitation of dendritic, axonal, and glial processes visualized through serial section electron microscopy. We developed a novel deep learning-based method to generate dense 3D segmentations rapidly from sparse 2D annotations of a few objects on single sections. Models trained on the rapidly generated segmentations achieved similar accuracy as those trained on expert dense ground-truth annotations. Human time to generate annotations was reduced by three orders of magnitude and could be produced by non-expert annotators. This capability will democratize generation of training data for large image volumes needed to achieve brain circuits and measures of circuit strengths.
RESUMEN
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.
Asunto(s)
Teoría de la Información , Plasticidad Neuronal , Sinapsis , Animales , Sinapsis/fisiología , Plasticidad Neuronal/fisiología , Espinas Dendríticas/fisiología , Región CA1 Hipocampal/fisiología , Modelos Neurológicos , Almacenamiento y Recuperación de la Información , Masculino , Hipocampo/fisiología , RatasRESUMEN
Long-term potentiation (LTP) has become a standard model for investigating synaptic mechanisms of learning and memory. Increasingly, it is of interest to understand how LTP affects the synaptic information storage capacity of the targeted population of synapses. Here, structural synaptic plasticity during LTP was explored using three-dimensional reconstruction from serial section electron microscopy. Storage capacity was assessed by applying a new analytical approach, Shannon information theory, to delineate the number of functionally distinguishable synaptic strengths. LTP was induced by delta-burst stimulation of perforant pathway inputs to the middle molecular layer of hippocampal dentate granule cells in adult rats. Spine head volumes were measured as predictors of synaptic strength and compared between LTP and control hemispheres at 30 min and 2 hr after the induction of LTP. Synapses from the same axon onto the same dendrite were used to determine the precision of synaptic plasticity based on the similarity of their physical dimensions. Shannon entropy was measured by exploiting the frequency of spine heads in functionally distinguishable sizes to assess the degree to which LTP altered the number of bits of information storage. Outcomes from these analyses reveal that LTP expanded storage capacity; the distribution of spine head volumes was increased from 2 bits in controls to 3 bits at 30 min and 2.7 bits at 2 hr after the induction of LTP. Furthermore, the distribution of spine head volumes was more uniform across the increased number of functionally distinguishable sizes following LTP, thus achieving more efficient use of coding space across the population of synapses.
RESUMEN
Morphology and function of the dorsolateral prefrontal cortex (dlPFC), and corresponding working memory performance, are affected early in the aging process, but nearly half of aged individuals are spared of working memory deficits. Translationally relevant model systems are critical for determining the neurobiological drivers of this variability. The common marmoset (Callithrix jacchus) is advantageous as a model for these investigations because, as a non-human primate, marmosets have a clearly defined dlPFC that enables measurement of prefrontal-dependent cognitive functions, and their short (â¼10 year) lifespan facilitates longitudinal studies of aging. Previously, we characterized working memory capacity in a cohort of marmosets that collectively covered the lifespan, and found age-related working memory impairment. We also found a remarkable degree of heterogeneity in performance, similar to that found in humans. Here, we tested the hypothesis that changes to synaptic ultrastructure that affect synaptic efficacy stratify marmosets that age with cognitive impairment from those that age without cognitive impairment. We utilized electron microscopy to visualize synapses in the marmoset dlPFC and measured the sizes of boutons, presynaptic mitochondria, and synapses. We found that coordinated scaling of the sizes of synapses and mitochondria with their associated boutons is essential for intact working memory performance in aged marmosets. Further, lack of synaptic scaling, due to a remarkable failure of synaptic mitochondria to scale with presynaptic boutons, selectively underlies age-related working memory impairment. We posit that this decoupling results in mismatched energy supply and demand, leading to impaired synaptic transmission. We also found that aged marmosets have fewer synapses in dlPFC than young, though the severity of synapse loss did not predict whether aging occurred with or without cognitive impairment. This work identifies a novel mechanism of synapse dysfunction that stratifies marmosets that age with cognitive impairment from those that age without cognitive impairment. The process by which synaptic scaling is regulated is yet unknown and warrants future investigation.
RESUMEN
Dendritic spines can be directly connected to both inhibitory and excitatory presynaptic terminals, resulting in nanometer-scale proximity of opposing synaptic functions. While dually innervated spines (DiSs) are observed throughout the central nervous system, their developmental timeline and functional properties remain uncharacterized. Here we used a combination of serial section electron microscopy, live imaging, and local synapse activity manipulations to investigate DiS development and function in rodent hippocampus. Dual innervation occurred early in development, even on spines where the excitatory input was locally silenced. Synaptic NMDA receptor currents were selectively reduced at DiSs through tonic GABAB receptor signaling. Accordingly, spine enlargement normally associated with long-term potentiation on singly innervated spines (SiSs) was blocked at DiSs. Silencing somatostatin interneurons or pharmacologically blocking GABABRs restored NMDA receptor function and structural plasticity to levels comparable to neighboring SiSs. Thus, hippocampal DiSs are stable structures where function and plasticity are potently regulated by nanometer-scale GABAergic signaling.
Asunto(s)
Espinas Dendríticas , Receptores de N-Metil-D-Aspartato , Espinas Dendríticas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Sinapsis/fisiología , Ácido gamma-Aminobutírico , Plasticidad Neuronal/fisiologíaRESUMEN
Microtubules deliver essential resources to and from synapses. Three-dimensional reconstructions in rat hippocampus reveal a sampling bias regarding spine density that needs to be controlled for dendrite caliber and resource delivery based on microtubule number. The strength of this relationship varies across dendritic arbors, as illustrated for area CA1 and dentate gyrus. In both regions, proximal dendrites had more microtubules than distal dendrites. For CA1 pyramidal cells, spine density was greater on thicker than thinner dendrites in stratum radiatum, or on the more uniformly thin terminal dendrites in stratum lacunosum moleculare. In contrast, spine density was constant across the cone shaped arbor of tapering dendrites from dentate granule cells. These differences suggest that thicker dendrites supply microtubules to subsequent dendritic branches and local dendritic spines, whereas microtubules in thinner dendrites need only provide resources to local spines. Most microtubules ran parallel to dendrite length and associated with long, presumably stable mitochondria, which occasionally branched into lateral dendritic branches. Short, presumably mobile, mitochondria were tethered to microtubules that bent and appeared to direct them into a thin lateral branch. Prior work showed that dendritic segments with the same number of microtubules had elevated resources in subregions of their dendritic shafts where spine synapses had enlarged, and spine clusters had formed. Thus, additional microtubules were not required for redistribution of resources locally to growing spines or synapses. These results provide new understanding about the potential for microtubules to regulate resource delivery to and from dendritic branches and locally among dendritic spines.
Asunto(s)
Dendritas , Espinas Dendríticas , Animales , Dendritas/fisiología , Hipocampo , Microtúbulos , Células Piramidales/fisiología , Ratas , Sinapsis/fisiologíaRESUMEN
Long-term potentiation (LTP) is a cellular mechanism of learning and memory that results in a sustained increase in the probability of vesicular release of neurotransmitter. However, previous work in hippocampal area CA1 of the adult rat revealed that the total number of vesicles per synapse decreases following LTP, seemingly inconsistent with the elevated release probability. Here, electron-microscopic tomography (EMT) was used to assess whether changes in vesicle density or structure of vesicle tethering filaments at the active zone might explain the enhanced release probability following LTP. The spatial relationship of vesicles to the active zone varies with functional status. Tightly docked vesicles contact the presynaptic membrane, have partially formed SNARE complexes, and are primed for release of neurotransmitter upon the next action potential. Loosely docked vesicles are located within 8 nm of the presynaptic membrane where SNARE complexes begin to form. Nondocked vesicles comprise recycling and reserve pools. Vesicles are tethered to the active zone via filaments composed of molecules engaged in docking and release processes. The density of tightly docked vesicles was increased 2 h following LTP compared to control stimulation, whereas the densities of loosely docked or nondocked vesicles congregating within 45 nm above the active zones were unchanged. The tethering filaments on all vesicles were shorter and their attachment sites shifted closer to the active zone. These findings suggest that tethering filaments stabilize more vesicles in the primed state. Such changes would facilitate the long-lasting increase in release probability following LTP.
Asunto(s)
Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Vesículas Sinápticas/ultraestructura , Animales , Encéfalo/metabolismo , Encéfalo/fisiología , Citoesqueleto , Tomografía con Microscopio Electrónico/métodos , Hipocampo/metabolismo , Potenciación a Largo Plazo/genética , Masculino , Neurotransmisores , Terminales Presinápticos/metabolismo , Terminales Presinápticos/fisiología , Ratas , Ratas Long-Evans , Sinapsis/fisiología , Membranas Sinápticas/fisiología , Membranas Sinápticas/ultraestructura , Vesículas Sinápticas/fisiologíaRESUMEN
Large scientific projects in genomics and astronomy are influential not because they answer any single question but because they enable investigation of continuously arising new questions from the same data-rich sources. Advances in automated mapping of the brain's synaptic connections (connectomics) suggest that the complicated circuits underlying brain function are ripe for analysis. We discuss benefits of mapping a mouse brain at the level of synapses.
Asunto(s)
Encéfalo/fisiología , Conectoma/métodos , Red Nerviosa/fisiología , Neuronas/fisiología , Sinapsis/fisiología , Animales , RatonesRESUMEN
Analysis of long-term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L-LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in the stratum radiatum of rat hippocampal area CA1. The goal here was to determine the developmental profile of synaptic plasticity leading to L-LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6J and Fmr1-/y on the C57BL/6J background, and 129SVE and Hevin-/- (Sparcl1-/- ) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse-induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10-P35 in the expression of short-term potentiation (STP), lasting ≤1 hr. In the 129SVE mice, L-LTP onset (>25% of slices) occurred by 3 weeks, reliable L-LTP (>50% slices) was achieved by 4 weeks, and Hevin-/- advanced this profile by 1 week. In the C57BL/6J mice, L-LTP onset occurred significantly later, over 3-4 weeks, and reliability was not achieved until 5 weeks. Although some of the Fmr1-/y mice showed L-LTP before 3 weeks, reliable L-LTP also was not achieved until 5 weeks. L-LTP onset was not advanced in any of the mouse genotypes by multiple bouts of theta-burst stimulation at 90 or 180 min intervals. These findings show important species differences in the onset of STP and L-LTP, which occur at the same age in rats but are sequentially acquired in mice.
Asunto(s)
Potenciales Postsinápticos Excitadores/fisiología , Hipocampo/crecimiento & desarrollo , Potenciación a Largo Plazo/fisiología , Plasticidad Neuronal/fisiología , Animales , Animales Recién Nacidos , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Técnicas de Cultivo de Órganos , Especificidad de la EspecieRESUMEN
Nature teaches us that form precedes function, yet structure and function are intertwined. Such is the case with synapse structure, function, and plasticity underlying learning, especially in the hippocampus, a crucial brain region for memory formation. As the hippocampus matures, enduring changes in synapse structure produced by long-term potentiation (LTP) shift from synaptogenesis to synapse enlargement that is homeostatically balanced by stalled spine outgrowth and local spine clustering. Production of LTP leads to silent spine outgrowth at P15, and silent synapse enlargement in adult hippocampus at 2hours, but not at 5 or 30min following induction. Here we consider structural LTP in the context of developmental stage and variation in the availability of local resources of endosomes, smooth endoplasmic reticulum and polyribosomes. The emerging evidence supports a need for more nuanced analysis of synaptic plasticity in the context of subcellular resource availability and developmental stage.
Asunto(s)
Espinas Dendríticas , Potenciación a Largo Plazo , Análisis por Conglomerados , Hipocampo , Plasticidad Neuronal , SinapsisAsunto(s)
Espinas Dendríticas/ultraestructura , Microscopía Electrónica/métodos , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Animales , Espinas Dendríticas/fisiología , Estimulación Eléctrica , Endosomas/ultraestructura , Hipocampo/crecimiento & desarrollo , Hipocampo/ultraestructura , Humanos , Imagenología Tridimensional , Potenciación a Largo Plazo/fisiología , Neuroglía/fisiología , Neuroglía/ultraestructura , Polirribosomas/ultraestructura , Ratas , Manejo de Especímenes/métodosRESUMEN
Analysis of neuronal compartments has revealed many state-dependent changes in geometry but establishing synapse-specific mechanisms at the nanoscale has proven elusive. We co-expressed channelrhodopsin2-GFP and mAPEX2 in a subset of hippocampal CA3 neurons and used trains of light to induce late-phase long-term potentiation (L-LTP) in area CA1. L-LTP was shown to be specific to the labeled axons by severing CA3 inputs, which prevented back-propagating recruitment of unlabeled axons. Membrane-associated mAPEX2 tolerated microwave-enhanced chemical fixation and drove tyramide signal amplification to deposit Alexa Fluor dyes in the light-activated axons. Subsequent post-embedding immunogold labeling resulted in outstanding ultrastructure and clear distinctions between labeled (activated), and unlabeled axons without obscuring subcellular organelles. The gold-labeled axons in potentiated slices were reconstructed through serial section electron microscopy; presynaptic vesicles and other constituents could be quantified unambiguously. The genetic specification, reliable physiology, and compatibility with established methods for ultrastructural preservation make this an ideal approach to link synapse ultrastructure and function in intact circuits.
Asunto(s)
Axones/efectos de la radiación , Axones/ultraestructura , Luz , Potenciación a Largo Plazo/efectos de la radiación , Optogenética , Animales , Axones/metabolismo , Axones/fisiología , Ratas , Sinapsis/metabolismo , Sinapsis/efectos de la radiaciónRESUMEN
The overarching goal of the NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is to advance the understanding of healthy and diseased brain circuit function through technological innovation. Core principles for this goal include the validation and dissemination of the myriad innovative technologies, tools, methods, and resources emerging from BRAIN-funded research. Innovators, BRAIN funding agencies, and non-Federal partners are working together to develop strategies for making these products usable, available, and accessible to the scientific community. Here, we describe several early strategies for supporting the dissemination of BRAIN technologies. We aim to invigorate a dialogue with the neuroscience research and funding community, interdisciplinary collaborators, and trainees about the existing and future opportunities for cultivating groundbreaking research products into mature, integrated, and adaptable research systems. Along with the accompanying Society for Neuroscience 2019 Mini-Symposium, "BRAIN Initiative: Cutting-Edge Tools and Resources for the Community," we spotlight the work of several BRAIN investigator teams who are making progress toward providing tools, technologies, and services for the neuroscience community. These tools access neural circuits at multiple levels of analysis, from subcellular composition to brain-wide network connectivity, including the following: integrated systems for EM- and florescence-based connectomics, advances in immunolabeling capabilities, and resources for recording and analyzing functional connectivity. Investigators describe how the resources they provide to the community will contribute to achieving the goals of the NIH BRAIN Initiative. Finally, in addition to celebrating the contributions of these BRAIN-funded investigators, the Mini-Symposium will illustrate the broader diversity of BRAIN Initiative investments in cutting-edge technologies and resources.
Asunto(s)
Neurociencias/métodos , Investigación , Tecnología , HumanosRESUMEN
Long-term potentiation (LTP), an increase in synaptic efficacy following high-frequency stimulation, is widely considered a mechanism of learning. LTP involves local remodeling of dendritic spines and synapses. Smooth endoplasmic reticulum (SER) and endosomal compartments could provide local stores of membrane and proteins, bypassing the distant Golgi apparatus. To test this hypothesis, effects of LTP were compared to control stimulation in rat hippocampal area CA1 at postnatal day 15 (P15). By two hours, small spines lacking SER increased after LTP, whereas large spines did not change in frequency, size, or SER content. Total SER volume decreased after LTP consistent with transfer of membrane to the added spines. Shaft SER remained more abundant in spiny than aspiny dendritic regions, apparently supporting the added spines. Recycling endosomes were elevated specifically in small spines after LTP. These findings suggest local secretory trafficking contributes to LTP-induced synaptogenesis and primes the new spines for future plasticity.
Asunto(s)
Región CA1 Hipocampal/fisiología , Potenciación a Largo Plazo , Plasticidad Neuronal , Vesículas Secretoras/metabolismo , Sinapsis/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Endosomas/metabolismo , RatasRESUMEN
Synapse clustering facilitates circuit integration, learning, and memory. Long-term potentiation (LTP) of mature neurons produces synapse enlargement balanced by fewer spines, raising the question of how clusters form despite this homeostatic regulation of total synaptic weight. Three-dimensional reconstruction from serial section electron microscopy (3DEM) revealed the shapes and distributions of smooth endoplasmic reticulum (SER) and polyribosomes, subcellular resources important for synapse enlargement and spine outgrowth. Compared to control stimulation, synapses were enlarged two hours after LTP on resource-rich spines containing polyribosomes (4% larger than control) or SER (15% larger). SER in spines shifted from a single tubule to complex spine apparatus after LTP. Negligible synapse enlargement (0.6%) occurred on resource-poor spines lacking SER and polyribosomes. Dendrites were divided into discrete synaptic clusters surrounded by asynaptic segments. Spine density was lowest in clusters having only resource-poor spines, especially following LTP. In contrast, resource-rich spines preserved neighboring resource-poor spines and formed larger clusters with elevated total synaptic weight following LTP. These clusters also had more shaft SER branches, which could sequester cargo locally to support synapse growth and spinogenesis. Thus, resources appear to be redistributed to synaptic clusters with LTP-related synapse enlargement while homeostatic regulation suppressed spine outgrowth in resource-poor synaptic clusters.
Asunto(s)
Espinas Dendríticas/metabolismo , Retículo Endoplásmico Liso/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Polirribosomas/metabolismo , Sinapsis/metabolismo , Animales , Espinas Dendríticas/ultraestructura , Retículo Endoplásmico Liso/ultraestructura , Hipocampo/ultraestructura , Masculino , Polirribosomas/ultraestructura , Ratas Long-Evans , Sinapsis/ultraestructura , Técnicas de Cultivo de TejidosRESUMEN
Hippocampal long-term potentiation (LTP) is a cellular memory mechanism. For LTP to endure, new protein synthesis is required immediately after induction and some of these proteins must be delivered to specific, presumably potentiated, synapses. Local synthesis in dendrites could rapidly provide new proteins to synapses, but the spatial distribution of translation following induction of LTP is not known. Here, we quantified polyribosomes, the sites of local protein synthesis, in CA1 stratum radiatum dendrites and spines from postnatal day 15 rats. Hippocampal slices were rapidly fixed at 5, 30, or 120 min after LTP induction by theta-burst stimulation (TBS). Dendrites were reconstructed through serial section electron microscopy from comparable regions near the TBS or control electrodes in the same slice, and in unstimulated hippocampus that was perfusion-fixed in vivo. At 5 min after induction of LTP, polyribosomes were elevated in dendritic shafts and spines, especially near spine bases and in spine heads. At 30 min, polyribosomes remained elevated only in spine bases. At 120 min, both spine bases and spine necks had elevated polyribosomes. Polyribosomes accumulated in spines with larger synapses at 5 and 30 min, but not at 120 min. Small spines, meanwhile, proliferated dramatically by 120 min, but these largely lacked polyribosomes. The number of ribosomes per polyribosome is variable and may reflect differences in translation regulation. In dendritic spines, but not shafts, there were fewer ribosomes per polyribosome in the slice conditions relative to in vivo, but this recovered transiently in the 5 min LTP condition. Overall, our data show that LTP induces a rapid, transient upregulation of large polyribosomes in larger spines, and a persistent upregulation of small polyribosomes in the bases and necks of small spines. This is consistent with local translation supporting enlargement of potentiated synapses within minutes of LTP induction.
Asunto(s)
Región CA1 Hipocampal/metabolismo , Potenciación a Largo Plazo/fisiología , Polirribosomas/ultraestructura , Biosíntesis de Proteínas/fisiología , Sinapsis/metabolismo , Animales , Región CA1 Hipocampal/ultraestructura , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Masculino , Ratas , Ratas Long-Evans , Sinapsis/ultraestructuraRESUMEN
An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.
Asunto(s)
Giro Dentado/fisiología , Potenciación a Largo Plazo , Sinapsis/fisiología , Animales , Masculino , Plasticidad Neuronal , Vía Perforante/fisiología , Ratas , Ratas Long-EvansRESUMEN
Mitochondria support synaptic transmission through production of ATP, sequestration of calcium, synthesis of glutamate, and other vital functions. Surprisingly, less than 50% of hippocampal CA1 presynaptic boutons contain mitochondria, raising the question of whether synapses without mitochondria can sustain changes in efficacy. To address this question, we analyzed synapses from postnatal day 15 (P15) and adult rat hippocampus that had undergone theta-burst stimulation to produce long-term potentiation (TBS-LTP) and compared them to control or no stimulation. At 30 and 120 min after TBS-LTP, vesicles were decreased only in presynaptic boutons that contained mitochondria at P15, and vesicle decrement was greatest in adult boutons containing mitochondria. Presynaptic mitochondrial cristae were widened, suggesting a sustained energy demand. Thus, mitochondrial proximity reflected enhanced vesicle mobilization well after potentiation reached asymptote, in parallel with the apparently silent addition of new dendritic spines at P15 or the silent enlargement of synapses in adults.