Interconnections between the dorsal thalamus and the basal nuclei in a reptile.

Reciprocal connections between the thalamus and the cortex are one of the most characteristic features of forebrain organization in mammals. To date, this circuit has been documented only in turtles. However, reptiles, including turtles, have an additional path from the dorsal thalamus to the telencephalon. This terminates in a pallial structure known as the dorsal ventricular ridge. Yet, no reciprocal connection from the dorsal ventricular ridge to thalamic nuclei has been uncovered. Since axons from the thalamus pass through the basal nuclei on route to the dorsal ventricular ridge, the basal nuclei might be a source of reciprocal connections. Accordingly, the location and distribution of neurons after retrograde tracer placement into the dorsal thalamus were examined. Retrogradely labeled neurons in the basal nuclei were indeed found. One possibility to explain this observation is that connections with the dorsal ventricular ridge are present during development but later pruned during embryogenesis.

Nuclei and tracts in the thalamus of crocodiles.

The thalamus is one of the most important divisions of the forebrain because it serves as the major hub for transmission of information between the brainstem and telencephalon. While many studies have investigated the thalamus in mammals, comparable analyses in reptiles are incomplete. To fill this gap in knowledge, the thalamus was investigated in crocodiles using a variety of morphological techniques. The thalamus consists of two parts: a dorsal and a ventral division. The dorsal thalamus was defined by its projections to the telencephalon, whereas the ventral thalamus lacked this circuit. The complement of nuclei in each part of the thalamus was identified and characterized. Alar and basal components of both the dorsal and ventral thalamus were distinguished. Although some alar-derived nuclei in the dorsal thalamus shared certain features, no grouping could account for all of the known nuclei. However, immunohistochemical observations suggested a subdivision of alar-derived ventral thalamic nuclei. In view of this, a different approach to the organization of the dorsal thalamus should be considered. Development of the dorsal thalamus is suggested to be one way to provide a fresh perspective on its organization.

Conserved patterns of functional organization between cortex and thalamus in mice.

Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical and subcortical inputs contribute to their distinct output pathways. We used subpopulation specific viral strategies in mice to anatomically and physiologically dissect pathways of the higher-order thalamic nuclei of the somatosensory and visual systems (the posterior medial nucleus and pulvinar). Employing a complementary optogenetics and electrical stimulation strategy, we show that synapses in cortex from higher-order thalamus have functionally divergent properties in primary vs. higher cortical areas. Higher-order thalamic projections onto excitatory targets in S1 and V1 were weakly modulatory, while projections to S2 and higher visual areas were strong drivers of postsynaptic targets. Then, using transsynaptic tracing verified by optogenetics to map inputs to higher-order thalamus, we show that posterior medial nucleus cells projecting to S1 are driven by neurons in layer 5 of S1, S2, and M1 and that pulvinar cells projecting to V1 are driven by neurons in layer 5 of V1 and higher visual areas. Therefore, in both systems, layer 5 of primary and higher cortical areas drives transthalamic feedback modulation of primary sensory cortex through higher-order thalamus. These results highlight conserved organization that may be shared by other thalamocortical circuitry. They also support the hypothesis that direct corticocortical projections in the brain are paralleled by transthalamic pathways, even in the feedback direction, with feedforward transthalamic pathways acting as drivers, while feedback through thalamus is modulatory.

Do crocodiles have a zona incerta?

In mammals, the zona incerta is thought to be involved in a number of behaviors: visceral activity, arousal, attention, and posture and locomotion. These diverse and complex features suggested that the zona incerta functions as a global or integrative node. Nevertheless, despite multiple investigations into its anatomy, physiology, and behavior in a variety of mammals, no specific character identifies the zona incerta besides its appearance in fiber-stained material and its relationship to surrounding structures. One such structure is the thalamic reticular nucleus whose caudal pole often contains some intermingled cells of the zona incerta. In crocodilians, the entopeduncular nucleus (ep) abuts the caudal pole of the thalamic reticular nucleus and displays different immunohistochemical properties and soma size when compared with neurons in the thalamic reticular nucleus itself. To determine if neurons in the ep differed from those in the thalamic reticular nucleus in Alligator mississippiensis, the ep was investigated using Golgi methodology. The morphology and soma size of neurons in the ep differed from those in the thalamic reticular nucleus and indicated that these two areas are indeed separate neuronal aggregates. Based on these data and the known relationships of the zona incerta to surrounding structures in mammals, the ep of crocodilians is suggested to be the counterpart of the zona incerta of mammals.

Thalamic reticular nucleus in Alligator mississippiensis: Soma and dendritic morphology.

The thalamic reticular nucleus (TRN) is a critical structure influencing information transfer to the forebrain. In crocodilians, the TRN shares many features with its mammalian counterpart. One area that has not been explored is how individual neurons in the crocodilian TRN compare with those found in mammals. In mammals, TRN neurons are aligned parallel to the external border of the dorsal thalamus, have their dendrites oriented perpendicular to the fibers in the internal capsule, have fine, filamentous dendritic appendages, are either bipolar or multipolar, and are commonly considered to be a homogeneous morphological population of cells. To investigate the cellular morphology of the TRN complex, a Golgi analysis was undertaken in Alligator mississippiensis. This study examined features that have been used in mammals. In Alligator, the four TRN divisions are the dorsal peduncular nucleus, the perireticular nucleus, the interstitial nucleus, and the neurons in the medial forebrain bundle associated with the interstitial nucleus. In crocodilians, the dorsal peduncular nucleus is homologous to the TRN of mammals. From the 1787 drawn neuron profiles in the traditional three planes of section, the following were concluded. First, neurons in each part of the TRN complex in Alligator were similar in morphology. Second, each part of the TRN complex of Alligator contained a heterogenous population of cells. These variations between the cellular morphology of the dorsal peduncular nucleus of crocodilians and the TRN of mammals are speculated to partly result from differences in forebrain organization.

The synaptic inputs and thalamic projections of two classes of layer 6 corticothalamic neurons in primary somatosensory cortex of the mouse.

Although corticothalamic neurons (CThNs) represent the largest source of synaptic input to thalamic neurons, their role in regulating thalamocortical interactions remains incompletely understood. CThNs in sensory cortex have historically been divided into two types, those with cell bodies in Layer 6 (L6) that project back to primary sensory thalamic nuclei and those with cell bodies in Layer 5 (L5) that project to higher-order thalamic nuclei and subcortical structures. Recently, diversity among L6 CThNs has increasingly been appreciated. In the rodent somatosensory cortex, two major classes of L6 CThNs have been identified: one projecting to the ventral posterior medial nucleus (VPM-only L6 CThNs) and one projecting to both VPM and the posterior medial nucleus (VPM/POm L6 CThNs). Using rabies-based tracing methods in mice, we asked whether these L6 CThN populations integrate similar synaptic inputs. We found that both types of L6 CThNs received local input from somatosensory cortex and thalamic input from VPM and POm. However, VPM/POm L6 CThNs received significantly more input from a number of additional cortical areas, higher order thalamic nuclei, and subcortical structures. We also found that the two types of L6 CThNs target different functional regions within the thalamic reticular nucleus (TRN). Together, our results indicate that these two types of L6 CThNs represent distinct information streams in the somatosensory cortex and suggest that VPM-only L6 CThNs regulate, via their more restricted circuits, sensory responses related to a cortical column while VPM/POm L6 CThNs, which are integrated into more widespread POm-related circuits, relay contextual information.

Differential development of myelin in zebra finch song nuclei.

Songbirds learn vocalizations by hearing and practicing songs. As song develops, the tempo becomes faster and more precise. In the songbird brain, discrete nuclei form interconnected myelinated circuits that control song acquisition and production. The myelin sheath increases the speed of action potential propagation by insulating the axons of neurons and by reducing membrane capacitance. As the brain develops, myelin increases in density, but the time course of myelin development across discrete song nuclei has not been systematically studied in a quantitative fashion. We tested the hypothesis that myelination develops differentially across time and song nuclei. We examined myelin development in the brains of the zebra finch (Taeniopygia guttata) from chick at posthatch day (d) 8 to adult (up to 147 d) in five major song nuclei: HVC (proper name), robust nucleus of the arcopallium (RA), Area X, lateral magnocellular nucleus of the anterior nidopallium, and medial portion of the dorsolateral thalamic nucleus (DLM). All of these nuclei showed an increase in the density of myelination during development but at different rates and to different final degrees. Exponential curve fits revealed that DLM showed earlier myelination than other nuclei, and HVC showed the slowest myelination of song nuclei. Together, these data show differential maturation of myelination in different portions of the song system. Such differential maturation would be well placed to play a role in regulating the development of learned song.

Afferent and efferent connections of the nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus.

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto-prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh-l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello-prethalamic fibers cross the midline twice to innervate the PTh-l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon.

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei.

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.

A multi-contrast MRI approach to thalamus segmentation.

Thalamic alterations occur in many neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Routine interventions to improve symptom severity in movement disorders, for example, often consist of surgery or deep brain stimulation to diencephalic nuclei. Therefore, accurate delineation of grey matter thalamic subregions is of the upmost clinical importance. MRI is highly appropriate for structural segmentation as it provides different views of the anatomy from a single scanning session. Though with several contrasts potentially available, it is also of increasing importance to develop new image segmentation techniques that can operate multi-spectrally. We hereby propose a new segmentation method for use with multi-modality data, which we evaluated for automated segmentation of major thalamic subnuclear groups using T1 -weighted, T2* -weighted and quantitative susceptibility mapping (QSM) information. The proposed method consists of four steps: Highly iterative image co-registration, manual segmentation on the average training-data template, supervised learning for pattern recognition, and a final convex optimisation step imposing further spatial constraints to refine the solution. This led to solutions in greater agreement with manual segmentation than the standard Morel atlas based approach. Furthermore, we show that the multi-contrast approach boosts segmentation performances. We then investigated whether prior knowledge using the training-template contours could further improve convex segmentation accuracy and robustness, which led to highly precise multi-contrast segmentations in single subjects. This approach can be extended to most 3D imaging data types and any region of interest discernible in single scans or multi-subject templates.

Historical controversies about the thalamus: from etymology to function.

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the "thalamus opticorum nervorum") to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo.

The network organization of rat intrathalamic macroconnections and a comparison with other forebrain divisions.

The thalamus is 1 of 4 major divisions of the forebrain and is usually subdivided into epithalamus, dorsal thalamus, and ventral thalamus. The 39 gray matter regions comprising the large dorsal thalamus project topographically to the cerebral cortex, whereas the much smaller epithalamus (2 regions) and ventral thalamus (5 regions) characteristically project subcortically. Before analyzing extrinsic inputs and outputs of the thalamus, here, the intrinsic connections among all 46 gray matter regions of the rat thalamus on each side of the brain were expertly collated and subjected to network analysis. Experimental axonal pathway-tracing evidence was found in the neuroanatomical literature for the presence or absence of 99% of 2,070 possible ipsilateral connections and 97% of 2,116 possible contralateral connections; the connection density of ipsilateral connections was 17%, and that of contralateral connections 5%. One hub, the reticular thalamic nucleus (of the ventral thalamus), was found in this network, whereas no high-degree rich club or clear small-world features were detected. The reticular thalamic nucleus was found to be primarily responsible for conferring the property of complete connectedness to the intrathalamic network in the sense that there is, at least, one path of finite length between any 2 regions or nodes in the network. Direct comparison with previous investigations using the same methodology shows that each division of the forebrain (cerebral cortex, cerebral nuclei, thalamus, hypothalamus) has distinct intrinsic network topological organization. A future goal is to analyze the network organization of connections within and among these 4 divisions of the forebrain.

Thalamus Optimized Multi Atlas Segmentation (THOMAS): fast, fully automated segmentation of thalamic nuclei from structural MRI.

The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders.

The Neural Tract Between the Hypothalamus and Basal Forebrain in the Ascending Reticular Activating System: A Diffusion Tensor Tractography Study.

OBJECTIVE: Ascending Reticular Activating System (ARAS) has a key role in consciousness. The ARAS is a complex network consisting of a portion of the brainstem reticular formation, nonspecific thalamic nuclei, hypothalamus, Basal Forebrain (BF), and cerebral cortex. We examined the reconstruction method and features of the neural tract between the hypothalamus and the BF in normal subjects, using Diffusion Tensor Tractography (DTT). METHODS: Twenty-three healthy subjects were recruited. The ARAS between the hypothalamus and the BF was reconstructed by two Regions of Interest (ROIs): 1) seed ROI - the isolated green portion for the BF on the color map, 2) target ROI - the hypothalamus on the axial image. DTT parameters of the ARAS between the hypothalamus and the BF were examined. RESULTS: Among 46 hemispheres in 23 normal subjects, 24 hemispheres (52.2 %) were identified in the ARAS between the hypothalamus and the BF. The reconstructed ARAS between the hypothalamus and the BF connected from the hypothalamus to the commissural level and anteriorly through the anterior commissure and then reached the BF. CONCLUSION: Using DTT, the ARAS between the hypothalamus and the BF was identified in normal subjects. Because the hypothalamus and BF are related to the regulation of wakefulness and sleep, our reconstruction method and results would be useful in the research on sleep and wakefulness aspects of consciousness.

In-vivo probabilistic atlas of human thalamic nuclei based on diffusion- weighted magnetic resonance imaging.

The thalamic nuclei are involved in many neurodegenerative diseases and therefore, their identification is of key importance in numerous clinical treatments. Automated segmentation of thalamic subparts is currently achieved by exploring diffusion-weighted magnetic resonance imaging (DW-MRI), but in absence of such data, atlas-based segmentation can be used as an alternative. Currently, there is a limited number of available digital atlases of the thalamus. Moreover, all atlases are created using a few subjects only, thus are prone to errors due to the inter-subject variability of the thalamic morphology. In this work, we present a probabilistic atlas of anatomical subparts of the thalamus built upon a relatively large dataset where the individual thalamic parcellation was done by employing a recently proposed automatic diffusion-based clustering method. Our analyses, comparing the segmentation performance between the atlas-based and the clustering method, demonstrate the ability of the provided atlas to substitute the automated diffusion-based subdivision in the individual space when the DW-MRI is not available.

A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology.

The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.

Thalamic Reticular Nucleus in Caiman crocodilus: Immunohistochemical Staining.

The thalamic reticular nucleus in reptiles, Caiman crocodilus, shares a number of morphological similarities with its counterpart in mammals. In view of the immunohistochemical properties of this nucleus in mammals and the more recently identified complexity of this neuronal aggregate in Caiman, this nucleus was investigated using a number of antibodies. These results were compared with findings described for other amniotes. The following antibodies gave consistent and reproducible results: polyclonal sheep anti-parvalbumin (PV), monoclonal mouse anti-PV, and polyclonal sheep anti-glutamic acid decarboxylase (GAD). In the transverse plane, this nucleus is divided into two. In each part, a compact group of cells sits on top of the fibers of the forebrain bundle with scattered cells among these fibers. In the lateral forebrain bundle, this neuronal aggregate is represented by the dorsal peduncular nucleus and the perireticular nucleus while, in the medial forebrain bundle, these parts are the interstitial nucleus and the scattered cells in this fiber tract. The results of this study are the following. First, the thalamic reticular nucleus of Caiman contains GAD(+) and PV(+) neurons, which is similar to what has been described in other amniotes. Second, the morphology and distribution of many GAD(+) and PV(+) neurons in the dorsal peduncular and perireticular nuclei are similar and suggest that these neurons colocalize these markers. Third, neurons in the interstitial nucleus and in the medial forebrain bundle are GAD(+) and PV(+). At the caudal pole of the thalamic reticular nucleus, PV immunoreactive cells predominated and avoided the central portion of this nucleus where GAD(+) cells were preferentially located. However, GAD(+) cells were sparse when compared with PV(+) cells. This immunohistochemically different area in the caudal pole is considered to be an area separate from the thalamic reticular nucleus.

Heterogeneous organization and connectivity of the chicken auditory thalamus (Gallus gallus).

The auditory ascending system contains parallel pathways in vertebrate brains. In chickens (Gallus gallus), three pathways arise from nucleus laminaris (NL), nucleus angularis (NA), and regio intermedius (RI) in the brainstem, innervating three subdivisions of the nucleus mesencephalicus lateralis pars dorsalis (MLd) in the midbrain. The current study reveals the segregation of these pathways in their subsequent projections to the nucleus ovoidalis (Ov) in the thalamus. Based on cytoarchitecture and myelin distribution, we identified seven Ov subregions, including five neuronal clusters within the Ov proper, the nucleus semilunaris parovoidalis (SPO), and the circum-ovoidalis (cOv). Immunocytochemistry further revealed that a ventromedial cluster of the Ov proper (Ovvm) contains unique cell types expressing α8 subunit nicotinic acetylcholine receptor, while SPO and cOv are characterized with expression of calcitonin-gene-related peptide and cholecystokinin. Tract tracing studies demonstrated that Ovvm is a major target of the NL-recipient zone of MLd, while the RI-recipient zone of MLd predominantly projects to a ventrolateral cluster of the Ov proper. Afferent inputs to the remaining regions of the Ov proper mostly arise from the NA-recipient zone of MLd. SPO and cOv receive a projection from the surrounding areas of MLd, named the nucleus intercollicularis. Importantly, the Ov proper, SPO and cOv all project to the Field L2 in the forebrain, the avian auditory cortex. Taken together, these results demonstrate that the avian auditory thalamus is a structurally and functionally heterogeneous structure, implicating an important role in generating novel representations for specific acoustic features.

The ascending projections of the nuclei of the descending trigeminal tract (nTTD) in the zebra finch (Taeniopygia guttata).

In our traditional view of the avian somatosensory system, input from the beak and head reaches the telencephalon via a disynaptic pathway, involving projections from the principal sensory nucleus (PrV) directly to nucleus basorostralis (previously called nucleus basalis), whereas input from the rest of the body follows a trisynatic pathway similar to that in mammals, involving projections from the dorsal column nuclei to the thalamus, and thence to somatosensory wulst. However, the role of the nuclei of the descending trigeminal tract (nTTD) in this scenario is unclear, partly because their ascending projections have been examined in only one species, the mallard duck. Here we examine the ascending projections of the nTTD in the zebra finch, using in vivo injections of biotinylated dextran amine and verification of projections by means of retrograde transport of the beta subunit of cholera toxin. The results show a high degree of interconnectivity within the nTTD, and that these nuclei project to PrV. We also find a projection from nTTD to the contralateral thalamic nucleus uvaeformis, a multi-sensory nucleus connected to the song system. Furthermore, our finding of a projection from nTTD to the contralateral somatosensory thalamic nucleus dorsalis intermedius ventralis anterior (DIVA) is consistent with the well-known projection in mammals from nTTD to the ventrobasal thalamus, suggesting that the ascending trigeminal pathways in birds and mammals are more similar than previously thought.