The Arousal-Related "Central Thalamus" Stimulation Site Simultaneously Innervates Multiple High-Level Frontal and Parietal Areas.

In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.

Selective presence of a giant saccular organelle in the axon initial segment of a subpopulation of layer V pyramidal neurons.

Recently it has been shown that a giant saccular organelle (GSO) of unknown function is present in the axon initial segment (AIS) of an uncharacterized population of pyramidal cells of the rodent neocortex. Using tract-tracing methods and immunocytochemistry, in the present study we show that in rodents this GSO is present in the AIS of subpopulations of layer V pyramidal neurons projecting to various subcortical, non-thalamic targets, including the spinal cord. GSO-containing neurons express SMI32 and some of them are under the control of the Thy-1 gene promoter. In addition, our results demonstrate that the GSO expresses the inositol 1,4,5-triphosphate receptor 1 (IP3R1) and the sarco (endo) plasmic reticulum Ca(2+) ATPase 2, both in rodent and human neocortex. These results indicate the involvement of the GSO in the regulation of Ca(2+) levels in the AIS in a particular subpopulation of layer V neurons that give rise to subcortical non-thalamic descending projections.

Unveiling the diversity of thalamocortical neuron subtypes.

Our current understanding of thalamocortical (TC) circuits is largely based on studies investigating so-called 'specific' thalamic nuclei, which receive and transmit sensory-triggered input to specific cortical target areas. TC neurons in these nuclei have a striking point-to-point topography and a stereotyped laminar pattern of termination in the cortex, which has made them ideal models to study the organization, plasticity, and development of TC circuits. However, despite their experimental importance, neurons within these nuclei only represent a fraction of all thalamic neurons and do not reflect the diversity of the TC neuron population. Here we review the distinct subtypes of projection neurons that populate the thalamus, both within and across anatomically-defined nuclei, with regard to differences in their morphology, input/output connectivity and target specificity, as well as more recent findings on their neuron type-specific gene expression and development. We argue that a detailed understanding of the biology of TC neurons is critical to understand the role of the thalamus in normal and pathological perception, voluntary movement, cognition and attention.

Mapping of fluorescent protein-expressing neurons and axon pathways in adult and developing Thy1-eYFP-H transgenic mice.

Transgenic mouse lines in which a fluorescent protein is constitutively expressed under the Thy1 gene promoter have become important models in cell biology and pathology studies of specific neuronal populations. As a result of positional insertion and/or copy number effects on the transgene, the populations expressing the fluorescent protein (eYFP+) vary markedly among the different mice lines. However, identification of the eYFP+ subpopulations has remained sketchy and fragmentary even for the most widely used lines such as Thy1-eYFP-H mice (Feng, G., Mellor, R.H., Bernstein, M., Keller-Peck, C., Nguyen, Q.T., Wallace, M., Nerbonne, J.M., Lichtman and J.W., Sanes. J.R. 2000. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41-51). Here, we provide a comprehensive mapping of labeled cell types throughout the central nervous system in adult and postnatal (P0-P30) Thy1-eYFP-H mice. Cell type identification was based on somatodendritic morphology, axon trajectories, and, for cortical cells, retrograde labeling with Fast Blue to distinguish between subpopulations with different axonal targets. In the neocortex, eYFP+ cells are layers 5 and 6 pyramidal neurons, whose abundance and sublaminar distribution varies markedly between areas. Labeling is particularly prevalent in the corticospinal cells; as a result, the pyramidal pathway axons are conspicuously labeled down to the spinal cord. Large populations of hippocampal, subicular and amygdaloid projection neurons are eYFP+ as well. Additional eYFP+ cell groups are located in specific brainstem nuclei. Present results provide a comprehensive reference dataset for adult and developmental studies using the Thy1-eYFP-H mice strain, and show that this animal model may be particularly suitable for studies on the cell biology of corticospinal neurons.

Thalamic input to distal apical dendrites in neocortical layer 1 is massive and highly convergent.

Input to apical dendritic tufts is now deemed crucial for associative learning, attention, and similar "feedback" interactions in the cerebral cortex. Excitatory input to apical tufts in neocortical layer 1 has been traditionally assumed to be predominantly cortical, as thalamic pathways directed to this layer were regarded relatively scant and diffuse. However, the sensitive tracing methods used in the present study show that, throughout the rat neocortex, large numbers (mean approximately 4500/mm(2)) of thalamocortical neurons converge in layer 1 and that this convergence gives rise to a very high local density of thalamic terminals. Moreover, we show that the layer 1-projecting neurons are present in large numbers in most, but not all, motor, association, limbic, and sensory nuclei of the rodent thalamus. Some layer 1-projecting axons branch to innervate large swaths of the cerebral hemisphere, whereas others arborize within only a single cortical area. Present data imply that realistic modeling of cortical circuitry should factor in a dense axonal canopy carrying highly convergent thalamocortical input to pyramidal cell apical tufts. In addition, they are consistent with the notion that layer 1-projecting axons may be a robust anatomical substrate for extensive "feedback" interactions between cortical areas via the thalamus.

[Diversity in thalamic relay neurons: evidence for "bottom-up" and "top-down" information flow in thalamocortical pathways]. / Nuevas perspectivas anatomofuncionales sobre las redes talamocorticales.

Thalamocortical (TC) pathways are still mainly understood as the gateway for ascending sensory-motor information into the cortex. However, it is now clear that a great many TC cells are involved in interactions between cortical areas via the thalamus. We review recent data, including our own, which demonstrate the generalized presence in rodent thalamus of two major TC cell types characterized, among other features, by their axon development, arborization and laminar targeting in the cortex. Such duality may allow inputs from thalamus to access cortical circuits via "bottom-up"-wired axon arbors or via "top-down"-wired axon arbors.