Biology subjects

Rosa, M. G. P.

Publications and source records attributed to Rosa, M. G. P..

At least 19 recordsLinked to original sources

bioRxiv2025

Highly Consistent Anatomical Asymmetry in a Small Primate Brain: Left is Always Larger in the Marmoset Monkey

Although lateralisation of brain function is relatively common in animals, this is rarely accompanied by overt anatomical asymmetries. In primates, morphological differences between the cerebral hemispheres are well established in Hominidae but have been regarded as subtler or inconsistent in other species. Here we demonstrate that the left hemisphere is reproducibly larger than the right hemisphere in one of the smallest primates, the marmoset. This asymmetry develops postnatally, persists throughout adult life, and is found in individuals from genetically isolated colonies. Voxel-based morphometry reveals that the larger left hemisphere is primarily due to differences in the volume of cortical areas linked to social cognition. This result challenges the notion that the development and evolution of marked morphological asymmetry between the hemispheres is linked to the evolution of large brains.

neuroscience↗

bioRxiv2025

From comparative connectomics to large-scale working memory modeling in macaque and marmoset

Although macaques and marmosets are both primates of choice for studying the brain mechanisms of cognition, they differ in key aspects of anatomy and behavior. Interestingly, recent connectomic analysis revealed that strong top-down projections from the prefrontal cortex to the posterior parietal cortex, present in macaques and important for executive function, are absent in marmosets. Here, we propose a consensus mapping that bridges the two species cortical atlases and allows for direct area-to-area comparison of their connectomes, which are then used to build comparative computational large-scale modeling of the frontoparietal circuit for working memory. We found that the macaque model exhibits resilience against distractors, a prerequisite for normal working memory function. By contrast, the marmoset model predicts a sensitivity to distractibility commonly observed behaviorally in this species. Surprisingly, this contrasting trend can be swapped by scaling intrafrontal and frontoparietal, and offer a credible prediction to the marmosets behavior in this specific task.

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bioRxiv2024

Giant pyramidal neurons of the primary motor cortex express vasoactive intestinal polypeptide (VIP), a known marker of cortical interneurons

Vasoactive intestinal polypeptide (VIP) is known to be present in a subclass of cortical interneurons that are involved in the disinhibition of excitatory pyramidal neurons. Here, using three different antibodies, we demonstrate that VIP is also present in the giant layer 5 pyramidal (Betz) neurons which are characteristic of the limb and axial representations of the marmoset primary motor cortex (cytoarchitectural area 4ab). No VIP staining was observed in smaller layer 5 pyramidal cells present in the primary motor facial representation (cytoarchitectural area 4c), or in premotor cortex (e.g. the caudal subdivision of the dorsal premotor cortex, A6DC), indicating the selective expression of VIP in Betz cells. The most intense VIP staining occurred in the largest Betz cells, located in the medial part of A4ab. VIP in Betz cells was colocalized with neuronal specific marker (NeuN) and a calcium-binding protein parvalbumin (PV). PV also intensely labelled axon terminals surrounding Betz cell somata. Whereas Betz cells bodies were located in layer 5, VIP-positive (VIP+) interneurons were more abundant in the superficial cortical layers. They constituted about 5-7% of total cortical neuronal population, with the highest density observed in area 4c. Our results demonstrate the expression of VIP in the largest excitatory neurons of the primate cortex, which may offer new functional insights into the role of VIP in the brain, and also provide opportunities for genetic manipulation of Betz cells.

neuroscience↗

bioRxiv2024

Distribution of calbindin-positive neurons across areas and layers of the marmoset cerebral cortex

The calcium-binding protein calbindin is selectively expressed in specific neuronal populations of the cerebral cortex, including major classes of inhibitory interneurons. We have charted the distribution of calbindin-positive (CB+) neurons across areas and layers of the entire marmoset cortex using a combination of immunohistochemistry, AI-based image segmentation, 3-dimensional reconstruction, and cytoarchitecture-aware registration. CB+ neurons formed 10-20% of the cortical neuronal population, occurring in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+ neurons concentrated in the supragranular layers, there were clear trends in laminar distribution: the relative density in infragranular layers increased with hierarchical level, and the density in layer 4 was lowest in areas involved in sensorimotor integration and action planning. These results reveal new aspects of the cytoarchitectural organization of the primate cortex and demonstrate an efficient approach to mapping the full distribution of neurochemically distinct cell types throughout the brain, readily applicable to most mammalian species and parts of the nervous system.

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bioRxiv2023

Naturalistic Movies and Encoding Analysis Redefine Areal Borders in Primate Visual Cortex

Accurate definition of the borders of cortical visual areas is essential for the study of neuronal processes leading to perception. However, data used for definition of areal boundaries has suffered from issues related to resolution, uniform coverage, or suitability for objective analysis, leading to ambiguity. Here, we present a novel approach that combines widefield optical imaging, presentation of naturalistic movies, and encoding model analysis, to objectively define borders in the primate extrastriate cortex. We applied this method to test conflicting hypotheses about the third-tier visual cortex, where areal boundaries have remained controversial. The results support a hypothesis whereby an area contains representations of both the upper and lower contralateral quadrants (DM) is located immediate anterior to V2, and unveil pronounced tuning preferences in the third-tier areas. High-density electrophysiological recordings with a Neuropixels probe confirm these findings. Our encoding-model approach offers a powerful, objective way to disambiguate areal boundaries.

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bioRxiv2023

Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys

Lesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterise the timing of these processes, by comparing the LGN of adult marmoset monkeys following various recovery times after unilateral V1 lesions. Observations in NeuN-stained sections obtained from animals with very short (3 days) recoveries showed that the volume and neuronal density in the LGN ipsilateral to the lesions were similar to those in the contralateral hemispheres. However, neuronal density in the LGN lesion projection zones (LPZ) dropped rapidly thereafter, with a loss of [~]50% of the population occurring within a month of the lesions. This level of neuronal loss was then sustained for the remainder of the range of recovery times, up to >3 years post-lesion. In comparison, shrinkage of the LGN progressed more gradually, not reaching a stable value until 6 months post lesion. We also determined the time course of the expression of the calcium-binding protein calbindin (CB) in magnocellular (M) and parvocellular (P) layer neurons, a recently described form of neurochemical plasticity triggered by V1 lesions. We found that CB expression could be detected in surviving M and P neurons as early as 1 month after a lesion, with the percentage of neurons showing this neurochemical phenotype showing subtle changes over 6 months. Our study shows that there is a limited time window for any possible interventions aimed at reducing secondary neuronal loss in the visual afferent pathways following damage to V1.

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bioRxiv2022

Variability of visual field maps in human early extrastriate cortex challenges the canonical model of organization of V2 and V3

Visual field maps in human early extrastriate areas (V2 and V3) are traditionally thought to form mirror-image representations which surround the primary visual cortex (V1). According to this scheme, V2 and V3 form nearly symmetrical halves with respect to the calcarine sulcus, with the dorsal halves representing lower contralateral quadrants, and the ventral halves representing upper contralateral quadrants. This arrangement is considered to be consistent across individuals, and thus predictable with reasonable accuracy using templates. However, data that deviate from this expected pattern have been observed, but mainly treated as artifactual. Here we systematically investigate individual variability in the visual field maps of human early visual cortex using the 7T Human Connectome Project (HCP) retinotopy dataset. Our results demonstrate substantial and principled inter-individual variability. Visual field representation in the dorsal portions of V2 and V3 was more variable than in their ventral counterparts, including substantial departures from the expected mirror-symmetrical patterns. In addition, left hemisphere retinotopic maps were more variable than those in the right hemisphere. Surprisingly, only one-third of individuals had maps that conformed to the expected pattern in the left hemisphere. Visual field sign analysis further revealed that in many individuals the area conventionally identified as dorsal V3 shows a discontinuity in the mirror-image representation of the retina, associated with a Y-shaped lower vertical representation. Our findings challenge the current view that inter-individual variability in early extrastriate cortex is negligible, and that the dorsal portions of V2 and V3 are roughly mirror images of their ventral counterparts.

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bioRxiv2022

Neural responses to broadband visual flicker in marmoset primary visual cortex

Temporal information is ubiquitous in natural vision and must be represented accurately in the brain to allow us to interact with a constantly changing world. Recent studies have employed a random stimulation paradigm to map the temporal response function (TRF) to luminance changes in the human EEG. This approach has revealed that the visual system, when presented with broadband visual input, actively selects distinct temporal frequencies, and retains their phase-information for prolonged periods of time. This non-linear response likely originates in primary visual cortex (V1), yet, so far it has not been investigated on a neural level. Here, we characterize the steady-state response to random broadband visual flicker in marmoset V1. In two experiments, we recorded from i) marmosets passively stimulated under general anesthesia, and ii) awake marmosets, under free viewing conditions. Our results show that LFP coupling to the stimulus was broadband and unselective under anesthesia, whereas in awake animals, it was restricted to two distinct frequency components, in the alpha and beta range. Within these frequency bands, coupling adhered to the receptive field (RF) boundaries of the local populations. The responses outside the RF did not provide evidence for a propagation of stimulus information across the cortex, contrary to results in human EEG studies. This result may be explained by short fixation durations, warranting further investigation. In summary, our findings show that during awake behavior V1 neural responses to broadband information are selective for distinct frequency bands, and that this selectivity is likely controlled actively by top-down mechanisms.

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bioRxiv2021

Integrated resource for functional and structural connectivity of the marmoset brain

Comprehensive integration of structural and functional connectivity data is required to model brain functions accurately. While resources for studying the structural connectivity of non-human primate brains already exist, their integration with functional connectivity data has remained unavailable. Here we present a comprehensive resource that integrates the most extensive awake marmoset resting-state fMRI data available to date (39 marmoset monkeys, 710 runs, 12117 mins) with previously published cellular-level neuronal tracing (52 marmoset monkeys, 143 injections) and multi-resolution diffusion MRI datasets. The combination of these data allowed us to (1) map the fine-detailed functional brain networks and cortical parcellations; (2) develop a deep-learning-based parcellation generator that preserves the topographical organization of functional connectivity and reflects individual variabilities, and (3) investigate the structural basis underlying functional connectivity by computational modeling. This resource will enable modeling structure-function relationships and facilitate future comparative and translational studies of primate brains.

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bioRxiv2021

Afferent connections of cytoarchitectural area 6M and surrounding cortex in the marmoset: putative homologues of the supplementary and pre-supplementary motor areas

Cortical projections to the caudomedial frontal cortex were studied using retrograde tracers in marmosets. We tested the hypothesis that cytoarchitectural area 6M includes homologues of the supplementary and pre-supplementary motor areas (SMA and preSMA) of other primates. We found that, irrespective of the injection sites location within 6M, over half of the labeled neurons were located in motor and premotor areas. Other connections originated in prefrontal area 8b, ventral anterior and posterior cingulate areas, somatosensory areas (3a and 1-2), and areas on the rostral aspect of the dorsal posterior parietal cortex. Although the origin of afferents was similar, injections in rostral 6M received higher percentages of prefrontal afferents, and fewer somatosensory afferents, compared to caudal injections, compatible with differentiation into SMA and preSMA. Injections rostral to 6M (area 8b) revealed a very different set of connections, with increased emphasis in prefrontal and posterior cingulate afferents, and fewer parietal afferents. The connections of 6M were also quantitatively different from those of M1, dorsal premotor areas, and cingulate motor area 24d. These results show that the cortical motor control circuit is conserved in simian primates, indicating that marmosets can be valuable models for studying movement planning and control.

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bioRxiv2020

Histology-Based Average Template of the Marmoset Cortex With Probabilistic Localization of Cytoarchitectural Areas

The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki-Monash, or NM template), representing a morphological average of 20 brains of young adult individuals, obtained by 3D reconstructions generated from Nissl-stained serial sections. The method used to generate the template takes into account morphological features of the individual brains, as well as the borders of clearly defined cytoarchitectural areas. This has resulted in a resource which allows direct estimates of the most likely coordinates of each cortical area, as well as quantification of the margins of error involved in assigning voxels to areas, and preserves quantitative information about the laminar structure of the cortex. We provide spatial transformations between the NM and other available marmoset brain templates, thus enabling integration with magnetic resonance imaging (MRI) and tracer-based connectivity data. The NM template combines some of the main advantages of histology-based atlases (e.g. information about the cytoarchitectural structure) with features more commonly associated with MRI-based templates (isotropic nature of the dataset, and probabilistic analyses). The underlying workflow may be found useful in the future development of brain atlases that incorporate information about the variability of areas in species for which it may be impractical to ensure homogeneity of the sample in terms of age, sex and genetic background. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/036632v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@11d61f6org.highwire.dtl.DTLVardef@a9156org.highwire.dtl.DTLVardef@1cbdc84org.highwire.dtl.DTLVardef@fa738c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA 3D template of the marmoset cortex representing the average of 20 individuals. C_LIO_LIThe template is based on Nissl stain and preserves information about cortical layers. C_LIO_LIProbabilistic mapping of areas, cortical thickness, and layer intensity profiles. C_LIO_LIIncludes spatial transformations to other marmoset brain atlases. C_LI AbbreviationsFor a list of areas and their abbreviations see Table S2.

neuroscience↗

bioRxiv2020

Structural attributes and principles of the neocortical connectome in the marmoset monkey

The marmoset monkey has become an important primate model in Neuroscience. Here we characterize salient statistical properties of inter-areal connections of the marmoset cerebral cortex, using data from retrograde tracer injections. We found that the connectivity weights are highly heterogeneous, spanning five orders of magnitude, and are log-normally distributed. The cortico-cortical network is dense, heterogeneous and has high specificity. The reciprocal connections are the most prominent and the probability of connection between two areas decays with their functional dissimilarity. The laminar dependence of connections defines a hierarchical network correlated with microstructural properties of each area. The marmoset connectome reveals parallel streams associated with different sensory systems. Finally, the connectome is spatially embedded with a characteristic length that obeys a power law as a function of brain volume across species. These findings provide a connectomic basis for investigations of multiple interacting areas in a complex large-scale cortical system underlying cognitive processes.

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bioRxiv2018

Neuronal distribution across the cerebral cortex of the marmoset monkey (Callithrix jacchus)

Using stereological analysis of NeuN-stained sections, we investigated neuronal density and number of neurons per column throughout the marmoset cortex. Estimates of mean neuronal density encompassed a greater than threefold range, from >150,000 neurons/ mm3 in the primary visual cortex to ~50,000 neurons/ mm3 in the piriform complex. There was a trend for density to decrease from posterior to anterior cortex, but also local gradients, which resulted in a complex pattern; for example, in frontal, auditory and somatosensory cortex neuronal density tended to increase towards anterior areas. Anterior cingulate, motor, premotor, insular and ventral temporal areas were characterized by relatively low neuronal densities. Analysis across the depth of the cortex revealed greater laminar variation of neuronal density in occipital, parietal and inferior temporal areas, in comparison with other regions. Moreover, differences between areas were more pronounced in the supragranular layers than in infragranular layers. Calculations of the number of neurons per unit column revealed a pattern that was distinct from that of neuronal density, including local peaks in the posterior parietal, superior temporal, precuneate, frontopolar and temporopolar regions. These results suggest that neuronal distribution in adult cortex result from a complex interaction of developmental/ evolutionary determinants and functional requirements.

neuroscience↗

bioRxiv2018

Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey

Until the late 20th Century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of the vertical meridian of the visual field labelled few or no cells in auditory cortex. We also placed 8 retrograde tracer injections involving core, belt and parabelt auditory areas, none of which revealed direct projections from V1. These results confirm the existence of a direct, nonreciprocal projection from auditory areas to V1 in a different primate species, which has evolved separately from the macaque for over 30 million years. The essential similarity of these observations between marmoset and macaque indicate that early-stage audiovisual integration is a shared characteristic of primate sensory processing.

neuroscience↗

bioRxiv2018

The hotspots in primate cortical brain evolution support supramodal cognitive flexibility

Primate cortical evolution has been characterized by massive and disproportionate expansion of a set of specific regions in the neocortex. The associated increase in neocortical neurons comes with a high metabolic cost, thus the functions served by these regions must have conferred significant evolutionary advantage. Here, across a series of experiments, we show that the evolutionary high-expanding hotspots - as estimated from patterns of evolutionary expansion from several primate species - share functional connections with different brain networks in a context-dependent manner. This capacity of the hotspots to connect flexibly with various specialized brain networks depending on particular cognitive requirements suggests that their selective growth and sustainment in evolution has been linked to their involvement in supramodal cognition. In accordance with an evolutionary-developmental view, we find that this ability to flexibly modulate functional connections as a function of cognitive state emerges gradually through childhood, with a prolonged developmental trajectory plateauing in young adulthood.

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bioRxiv2018

A High-throughput Neurohistological Pipeline for Brain-Wide Mesoscale Connectivity Mapping of the Common Marmoset

Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. MRI based methods offer whole brain coverage, but remain indirect in the approach to connectivity mapping. Recent progress has been made in directly mapping whole-brain connectivity architecture in the mouse at the mesoscopic scale. The basic approach uses tracer injections systematically placed on a grid of locations spanning the brain and computational analysis of the resulting whole brain data sets. Scaling this approach to bigger primate brains poses nontrivial technical challenges. Here we present an integrated neurohistological pipeline as well as a grid-based tracer injection strategy for systematic mesoscale connectivity mapping in the common Marmoset (Callithrix jacchus). Individual brains are sectioned into [~]1700 20{micro}m sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labelled sections. Combining the resulting 3D volumes, containing informative cytoarchitectonic markers, with in-vivo and ex-vivo MRI, and using an integrated computational pipeline, we are able to overcome the significant individual variation exhibited by Marmosets to obtain routine and high quality maps to a common atlas framework. This will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain. While component instruments or protocols may be available from previous work, we believe that this is the first detailed systems-level presentation of the methodology required for high-throughput neuroanatomy in a model primate.

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bioRxiv2017

Altered sensitivity to motion of area MT neurons following long-term V1 lesions

The middle temporal area (MT) receives its main afferents from the striate cortex (V1). However, MT also receives direct thalamic projections, which have been hypothesized to play a crucial role in residual vision after V1 lesions. MT neurons continue to respond shortly after V1 lesions, but human clinical work has shown that lesion effects can take up to six months to stabilize, making it important to understand MT responses after long-term deprivation of V1 inputs. We recorded neuronal responses in MT to moving dot stimuli in adult marmoset monkeys, 7-11 months after unilateral V1 lesions. Fewer MT neurons were direction selective, including neurons whose locations corresponded to the intact parts of V1. Firing rates were higher and more variable, and increased with motion strength regardless of direction. These properties could be re-created by a network model with imbalanced inhibition and excitation, providing the first insights into functional implications of long-term plasticity in MT following V1 lesions.

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bioRxiv2017

The most informative neural code accounts for population heterogeneity

Perception is produced by reading out the representation of a sensory stimulus contained in the firing rates of a population of neurons. To examine experimentally how populations code information, a common approach is to decode a linearly-weighted sum of the neurons firing rates. This approach is popular because of its biological validity: weights in a computational decoder are analogous to synaptic strengths. For neurons recorded in vivo, weights are highly variable when derived through machine learning methods, but it is unclear what neuronal properties explain this variability, and how the variability affects decoding performance. To address this, we recorded from neurons in the middle temporal area (MT) of anesthetized marmosets (Callithrix jacchus) viewing stimuli comprising a sheet of dots that moved coherently in one of twelve different directions. We found that high gain and direction selectivity both predicted that a neuron would be weighted more highly in an optimised decoding model. Although learned weights differed markedly from weights chosen according to a priori rules based on a neurons tuning profile, decoding performance was only marginally better for the learned weights. In the models with a priori rules, selectivity is the best predictor of weighting, and defining weights according to a neurons preferred direction and selectivity improves decoding performance to very near the maximum level possible, as defined by the learned weights.\n\nNew & NoteworthyWe examined which aspects of a neurons tuning account for its contribution to sensory coding. Strongly direction-selective neurons were weighted most highly by machine learning algorithms trained to discriminate motion direction. Models with a priori defined decoding weights demonstrate that the learned weighting scheme causally improved direction representation by a neuronal population. Optimising decoders (using machine learning) lead to only marginally better performance than decoders based purely on a neurons preferred direction and selectivity.

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