Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. Here we present an integrated neuro-histological 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 µm sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labeled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments.
Further, by 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 accurately map individual brains into a common reference atlas despite the significant individual variation. This approach will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain. The connectional architecture of the brain underlies all the nervous system functions, yet our knowledge of detailed brain neural connectivity falls largely behind genomics and behavioral studies in humans and in model research species such as rodents (). To fill this critical gap, a coherent approach for the mapping of whole-brain neural circuits at the mesoscale using standardized methodology was proposed in 2009 (). Since then, several systematic brain connectivity mapping projects for the mouse have been initialized and established, including the Mouse Brain Architecture Project () (), the Allen Mouse Brain Connectivity Atlas () (connectivity.brain-map.org), and the Mouse Connectome Project ( (). Non-human primates (NHPs) were also proposed as an important group in which to study whole-brain neural architecture.
However, the high-throughput experimental approaches for mouse do not automatically apply to NHPs due to bioethical as well as experimental considerations, larger brain sizes coupled with stringent limitations on the numbers, as well as limitations arising from the increased individual variability of the brains. There has been an increase in the usage of the common marmoset ( Callithrix jacchus) as a model organism in contemporary neuroscience research (;;;; ) (). Marmosets offer a number of experimental advantages over the macaque, including lower cost, ease of handling and breeding (; ), smaller brain sizes (≈35 mm*25 mm*20 mm) that potentially allow more comprehensive analysis of the neuronal circuitry, and importantly the development of transgenic marmosets and the application of modern molecular tools (;; ). Marmosets are New World monkeys, in contrast with the Old World macaque monkeys which are the pre-eminent NHP models used in basic and pre-clinical neuroscience research.
As depicted in, New World monkeys, together with Old World monkeys, apes and humans, form the simian primates (order Primates, infraorder Simiiformes). The tiger and the snow torrent full. Simians diverged from prosimians such as lemurs and lorises approximately 85 million years ago (Mya). Among the simians, New World monkeys have evolved in isolation from Old World monkeys, apes and humans for at least 40 million years. Prima facie this seems to indicate a relative weakness in using marmosets as NHP models in contrast with the macaques. Nevertheless, a good case can be made for marmosets as NHP models of humans, despite the earlier evolutionary divergence. ( a) Phylogenetic tree (;;;;;;; ) showing the ancestral history of extinct and extant primates, after divergence from the common ancestor with rodents (top right inset box) ca. 75 million years (Myr) ago.
Dog anatomy comprises the anatomical studies of the visible parts of the body of a canine. Details of structures vary tremendously from breed to breed, more than in any other animal species, wild or domesticated, [1] as dogs are highly variable in height and weight.
The bottom bar shows geological eras. Thickness of spindle shaped areas in the evolutionary tree indicate prosperity (estimated population and numbers of species) of the group along the history in extinct (gray) prosimian (red) and simian (blue) primates.
Each bifurcation represents the species divergence, although the divergence time typically has a wide range and remains controversial. Primates diverged into platyrrhini, the New World Monkey, and catarrini, around 38.9–56.5 million years ago. Catarrini further evolved into Ape, including humans, and Old World Monkey as well as macaque monkeys 25.1–37.7 million years ago. Sketches of the brain in each species are shown on the right, next to their species name. The colored areas in the various brain illustrations indicate the primary visual area as green, somatosensory as purple, and auditory areas as red; each represents an extant primate (bottom right row) and rodent (top inset box) species’ body weight (first numbers in brackets) and brain weight (last numbers in brackets) sizes (;; ). Phylogenetic tree adapted from Masanaru Takai (). ( b) Fractional brain region volumes, and numbers of injection sites used in grid- based injection plans for marmoset () and mouse ().
Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. Here we present an integrated neuro-histological 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 µm sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labeled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments.
Further, by 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 accurately map individual brains into a common reference atlas despite the significant individual variation. This approach will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain. The connectional architecture of the brain underlies all the nervous system functions, yet our knowledge of detailed brain neural connectivity falls largely behind genomics and behavioral studies in humans and in model research species such as rodents (). To fill this critical gap, a coherent approach for the mapping of whole-brain neural circuits at the mesoscale using standardized methodology was proposed in 2009 (). Since then, several systematic brain connectivity mapping projects for the mouse have been initialized and established, including the Mouse Brain Architecture Project () (), the Allen Mouse Brain Connectivity Atlas () (connectivity.brain-map.org), and the Mouse Connectome Project ( (). Non-human primates (NHPs) were also proposed as an important group in which to study whole-brain neural architecture.
However, the high-throughput experimental approaches for mouse do not automatically apply to NHPs due to bioethical as well as experimental considerations, larger brain sizes coupled with stringent limitations on the numbers, as well as limitations arising from the increased individual variability of the brains. There has been an increase in the usage of the common marmoset ( Callithrix jacchus) as a model organism in contemporary neuroscience research (;;;; ) (). Marmosets offer a number of experimental advantages over the macaque, including lower cost, ease of handling and breeding (; ), smaller brain sizes (≈35 mm*25 mm*20 mm) that potentially allow more comprehensive analysis of the neuronal circuitry, and importantly the development of transgenic marmosets and the application of modern molecular tools (;; ). Marmosets are New World monkeys, in contrast with the Old World macaque monkeys which are the pre-eminent NHP models used in basic and pre-clinical neuroscience research.
As depicted in, New World monkeys, together with Old World monkeys, apes and humans, form the simian primates (order Primates, infraorder Simiiformes). The tiger and the snow torrent full. Simians diverged from prosimians such as lemurs and lorises approximately 85 million years ago (Mya). Among the simians, New World monkeys have evolved in isolation from Old World monkeys, apes and humans for at least 40 million years. Prima facie this seems to indicate a relative weakness in using marmosets as NHP models in contrast with the macaques. Nevertheless, a good case can be made for marmosets as NHP models of humans, despite the earlier evolutionary divergence. ( a) Phylogenetic tree (;;;;;;; ) showing the ancestral history of extinct and extant primates, after divergence from the common ancestor with rodents (top right inset box) ca. 75 million years (Myr) ago.
Dog anatomy comprises the anatomical studies of the visible parts of the body of a canine. Details of structures vary tremendously from breed to breed, more than in any other animal species, wild or domesticated, [1] as dogs are highly variable in height and weight.
The bottom bar shows geological eras. Thickness of spindle shaped areas in the evolutionary tree indicate prosperity (estimated population and numbers of species) of the group along the history in extinct (gray) prosimian (red) and simian (blue) primates.
Each bifurcation represents the species divergence, although the divergence time typically has a wide range and remains controversial. Primates diverged into platyrrhini, the New World Monkey, and catarrini, around 38.9–56.5 million years ago. Catarrini further evolved into Ape, including humans, and Old World Monkey as well as macaque monkeys 25.1–37.7 million years ago. Sketches of the brain in each species are shown on the right, next to their species name. The colored areas in the various brain illustrations indicate the primary visual area as green, somatosensory as purple, and auditory areas as red; each represents an extant primate (bottom right row) and rodent (top inset box) species’ body weight (first numbers in brackets) and brain weight (last numbers in brackets) sizes (;; ). Phylogenetic tree adapted from Masanaru Takai (). ( b) Fractional brain region volumes, and numbers of injection sites used in grid- based injection plans for marmoset () and mouse ().