Biology subjects

Garcia-Marin, V.

Publications and source records attributed to Garcia-Marin, V..

5 recordsLinked to original sources

bioRxiv2025

Three-dimensional ultrastructural differences between thalamic and non-thalamic recipient layers in macaque V1

Understanding the synaptic characteristics of each cortical layer is essential for elucidating the functional architecture of each brain region. In the current study, we made a detailed quantitative comparison of the synaptic structure in the predominantly input layers of primate primary visual cortex (layer 4C) and in the predominant output layer (layer 3B) using focused ion beam scanning electron microscopy (FIB/SEM). We quantified the synaptic density in each layer, classified synaptic boutons according to their number of synapses and mitochondrial content, and quantified key morphometric parameters, including bouton volume, postsynaptic density (PSD) area and morphology, volume occupied by mitochondria, and postsynaptic targets. Our results revealed that for all the layers there is a higher proportion of single-synapse boutons without mitochondria. Multisynaptic boutons containing mitochondria (MSBm+)-- which likely correspond to TC terminals --were significantly more abundant in the thalamocortical recipient layers 4C and 4C{beta}. These MSBm+ boutons were also larger, more likely to contact dendritic spines, and contained more mitochondria than other bouton categories. In contrast, layer 3B, displayed a lower prevalence of MSBm+ boutons, these boutons were smaller than those in layer 4C and made fewer synapses. These findings highlight laminar differences in bouton architecture and support the idea that TC synapses are structurally adapted to support high synaptic efficacy. Together, our data provide a detailed quantitative framework for understanding the synaptic organization of primate V1, with implications for sensory processing and cortical circuit function.

neuroscience↗

bioRxiv2023

High density aromatic peptides protect retinal ganglion cells in mouse retina following optic nerve crush injury.

Mitochondrial dysfunction is a critical early driver of retinal ganglion cell (RGC) loss in optic nerve injury. We evaluated whether HDAP2, a mitochondria-targeted aromatic peptide designed to support mitochondrial membrane integrity, could preserve neuronal structure after optic nerve crush (ONC). Systemically administered HDAP2 penetrated the blood-retinal barrier and localized to RGCs and mitochondrial-rich retinal layers. Daily treatment (IP, 3 mg/kg for 14 days) significantly improved RGC survival compared to saline-treated ONC animals. RGC densities increased across central, midperipheral, and peripheral regions, and surviving RGCs exhibited approximately two-fold higher RBPMS expression, suggesting improved cellular health. Transmission electron microscopy revealed that HDAP2 substantially reduced mitochondrial loss within crushed optic nerve axons. Mitochondrial density in HDAP2-treated nerves reached 70% of uninjured levels (0.129 {+/-} 0.029 vs. 0.185 {+/-} 0.017) and was 5.3-fold higher than untreated ONC nerves (0.025 {+/-} 0.012; Kruskal-Wallis p = 0.039; Cohens d = 2.77). Mitochondrial morphology was similar across groups, indicating that HDAP2 prevents mitochondrial loss rather than rescuing damaged organelles. HDAP2-treated nerves also contained a higher density of structurally intact axons, consistent with reduced ultrastructural degeneration following injury. These findings demonstrate that HDAP2 limits mitochondrial loss and attenuates neuronal degeneration after ONC. Together, the results support HDAP2 as a promising therapeutic candidate for protecting CNS projection neurons by maintaining mitochondrial stability after axonal injury.

neuroscience↗

bioRxiv2023

Targeting high-density aromatic peptides to cardiolipin optimizes the mitochondrial membrane potential.

The mitochondrial membrane potential ({Delta}{Psi}m) is created by the accumulation of protons on an outer leaflet of the inner mitochondrial membrane and drives the synthesis of most cellular ATP, which is essential for cellular bioenergetics and survival. The {Delta}{Psi}m also facilitates the electrogenic transport of cations, such as Ca2+, and regulates generation of reactive oxygen species, which serves as a powerful bioenergetic and stress-signaling regulator. Proton trapping on the outer leaflet of the inner mitochondrial membrane of mitochondrial cristae could be controlled by cardiolipin when the local pH is above 8. However, there is presently no technology that effectively targets strong bases to cardiolipin. We have developed a novel, high-density aromatic peptide (HDAP2) to preserve a proton gradient-driven potential in mitochondria by increasing proton trapping on cardiolipin (CL). HDAP2-induced formation of cardiolipin-HDAP2 complexes accumulated positive charges at the head of CL. The HDAP2-CL vesicles could accumulate the mitochondrial transmembrane potential probe, Tetramethylrhodamine (TMRM). This potential could be uncoupled with Carbonyl cyanide m-chlorophenylhydrazone (CCCP) and Dinitrophenol (DNP), indicating that an interaction of HDAP2 with CL could support a proton gradient-driven transmembrane potential. We demonstrated that this novel, water-soluble peptide is cell-permeable, targets mitochondria without causing cell toxicity, and promotes cell survival during serum starvation. Importantly, the HDAP2-cardiolipin complex-mediated optimization of the proton gradient was supported by the ability of HDAP2 to prevent CCCP-mediated mitochondrial depolarization in ARPE-19 cells in a dose-dependent manner. Based on its mechanism of action, HDAP2 could promote cellular homeostasis, which would have broad clinical applicability for the prevention, recovery and reversal of many acute and chronic disease conditions, such as neurodegeneration, ischemia- reperfusion injury, and inflammation.

biochemistry↗

bioRxiv2023

Neuronal composition of processing modules in human V1: laminar density for neuronal and non-neuronal populations and a comparison with macaque

The neuronal composition of homologous brain regions in different primates is important for understanding their processing capacities. Primary visual cortex (V1) has been widely studied in different members of the Catarrhines or Old-World monkeys. Neuronal density is considered to be central in defining the structure--function relationship. In human, there are large variations in the reported neuronal density from prior studies. We found the neuronal density in human V1 was 79,000 neurons/mm3, which is 35% of the neuronal density previously determined in macaque V1. Laminar density was proportionally similar between human and macaque. In V1, the ocular dominance column (ODC) contains the circuits for the emergence of orientation preference and spatial processing of a point image in many mammalian species. Analysis of the total neurons in an ODC and of the full number of neurons in macular vision (the central 15 degrees) indicate that humans have 1.28 times more neurons than macaques even though the density of neurons in macaque is 3 times the density in human V1. We propose that the number of neurons in a functional processing unit rather than the number of neurons under a mm2 of cortex is more appropriate for cortical comparisons across species.

neuroscience↗

bioRxiv2019

Functional clusters of neurons in layer 6 of macaque V1

AbstracLayer 6 appears to perform a very important role in the function of macaque primary visual cortex, V1, but not enough is understood about the functional characteristics of neurons in the layer 6 population. It is unclear to what extent the population is homogeneous with respect to their visual properties or if one can identify distinct sub-populations. Here we performed a cluster analysis based on measurements of the responses of single neurons in layer 6 of primary visual cortex to achromatic grating stimuli that varied in orientation, direction of motion, spatial and temporal frequency, and contrast. The visual stimuli were presented in a stimulus window that was also varied in size. Using the responses to parametric variation in these stimulus variables we extracted a number of tuning response measures and used them in the cluster analysis. Six main clusters emerged along with some smaller clusters. Additionally we asked whether parameter distributions from each of the clusters were statistically different. There were clear separations of parameters between some of the clusters, particularly for f1/f0 ratio, direction selectivity, and temporal frequency bandwidth but other dimensions also showed differences between clusters. Our data suggest that in layer 6, across the spatial extent of a single cortical hypercolumn, there are multiple parallel circuits that provide information about different aspects of the visual stimulus.

neuroscience↗