3D Synaptic Organization of the Rat CA1 and Alterations Induced by Cocaine Self-Administration

Blázquez-Llorca, Lidia; Miguéns, Miguel; Montero-Crespo, Marta; Selvas, Abraham; González‐Soriano, Juncal; Ambrosio, Emilio; DeFelipe, Javier

doi:10.1093/cercor/bhaa331

Cited by 5 publications

(5 citation statements)

References 129 publications

(94 reference statements)

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“…The proportion of AS to SS in the present study (97.1/2.9) is also similar to the previously calculated proportion (97.5/2.5) (Santuy et al, 2020), or the reported 3% of inhibitory synapses in thin dendrites, which predominate in our sample (Megías et al, 2001). The density of synapses in the rat SR is about 2.2 to 2.5 synapses/µm 3 (Blazquez-Llorca et al, 2021; Mishchenko et al, 2010; Sorra et al, 1998). In L1 and L3, we found synaptic densities of 1.80 and 1.08 synapses /µm 3 , respectively, that is, clearly lower than in the SR.…”

Section: Discussionmentioning

confidence: 99%

Nanoconnectivity: a quantitative approach to examine the structural complexity of the brain

Turégano-Lopez,

de las Pozas,

Santuy

et al. 2023

Preprint

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Unraveling the highly complex connectivity at the synaptic level is critical for the understanding of brain function. However, investigating the structure of the brain is time consuming and technically demanding. We have developed and applied a tracing method that allows us to obtain a simplified or skeletonized version of all nerve fibers present within a given brain sample, without the need for full 3D reconstructions. Every tracing or “skeleton” is linked to its corresponding synaptic contacts, so the result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. The tissue sample is obtained by volume electron microscopy (FIB-SEM) and tracing is performed by dedicated software. In addition, the software provides the length of each skeleton as well as the number and positions of its corresponding synapses. With this approach, we have identified clear as well as subtle quantitative differences between three brain regions (the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex). For example, we have found that axons and dendrites are densely packed in the neuropil of these three regions, reaching close to 8 kilometers of nerve fibers per cubic mm in layer 1. In all cases, the predominant fibers were excitatory axons, followed by spiny dendrites, inhibitory axons and smooth dendrites. Other examples include the fact that the excitatory axons in the stratum radiatum establish many more synapses per micron than the axons of the other regions, or the lack of correlation between the number of synapses established on the spines of a given dendrite and the number of synapses established on the dendritic shaft. Using this methodology, we obtain a set of quantitative parameters including the number and proportions of excitatory and inhibitory synapses; the numbers of dendrites and axons; the proportion of excitatory and inhibitory axons; the linear densities of synapses established on dendritic spines and dendritic shafts; the linear densities of synapses established by excitatory and inhibitory axons; and the lengths of the different types of dendrites and axons. Taken together, these data characterize each region, allowing us to compare them on a quantitative basis and to identify subtle traits and differences that would have escaped a qualitative analysis. With this strategy, we can achieve a better understanding of the structure and dynamics of the brain, and we are better equipped to explore how they change during both normal and pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Nanoconnectivity: a quantitative approach to examine the structural complexity of the brain

Turégano-Lopez,

de las Pozas,

Santuy

et al. 2023

Preprint

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show abstract

“…The proportion of AS to SS in the present study (97.1/2.9) is also similar to the previously calculated proportion (97.5/2.5) 48 , or the reported 3% of inhibitory synapses in thin dendrites, which predominate in our sample 49 . The density of synapses in the rat SR is about 2.2–2.5 synapses/µm 3 50 – 52 . In L1 and L3, we found synaptic densities of 1.80 and 1.08 synapses/µm 3 , respectively, that is, clearly lower than in the SR.…”

Section: Discussionmentioning

confidence: 98%

Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity

Turegano-Lopez,

de las Pozas,

Santuy

et al. 2024

Commun Biol

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The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified “skeleton” of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.

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“…Almost all (91-99%) spinous synapses in the CA1 and cortex of rodents and primates are excitatory. 66 , 71 , 72 , 73 , 74 , 75 , 76 In adult rat CA1, 100% of perforated and 64% of nonperforated synapses contain AMPA receptors, and 100% of both subtypes contain NMDA receptors. 67 , 77 Similarly, atypically large nonperforated synapses in adult rat CA1 contain more AMPA and NMDA receptors than typical nonperforated spinous synapses (Nicholson & Geinisman 2009).…”

Section: Discussionmentioning

confidence: 99%

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Fehr¹,

Janssen²,

Park³

et al. 2022

iScience

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3D Synaptic Organization of the Rat CA1 and Alterations Induced by Cocaine Self-Administration

Cited by 5 publications

References 129 publications

Nanoconnectivity: a quantitative approach to examine the structural complexity of the brain

Nanoconnectivity: a quantitative approach to examine the structural complexity of the brain

Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

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