Association Thalamic Nuclei Research Articles

Auditory MMN is associated with the volume of thalamic higher order nuclei in individuals with psychotic disorders and healthy controls.

Predictive coding is a theoretical framework that integrates models of brain dysconnectivity and psychopathology in psychosis. Thalamocortical dysconnectivity as well as reduced thalamic volumes have been reported in psychotic disorders. However, the role of the thalamus in predictive coding is not clear. We examined the relationship between magnetic resonance imaging (MRI)- based thalamic nuclei volumes and mismatch negativity (MMN), a purported index of prediction error signaling known to be impaired in psychosis. We obtained MRI and MMN using a roving paradigm from individuals with SCZ spectrum disorder (SSD, n=60) or bipolar disorder (BD, n=69) and HC (n=252). We segmented volumes of 25 thalamic nuclei bilaterally and tested their associations with MMN amplitude using linear models while covarying for age, sex, diagnosis, and intracranial volumes (ICV). We did not find group differences in thalamic volumes that could account for differences in MMN, neither did we find significant volume × diagnosis interactions on MMN for any of the 25 nuclei examined. Across the whole sample, significant positive associations were found between MMN amplitude and the volumes of several higher-order thalamic nuclei, including the mediodorsal medial and lateral nuclei, anterior and medial pulvinar, nucleus reuniens, as well as the lateral geniculate nucleus. The results demonstrate a positive association between MMN amplitude and volumes of thalamic association nuclei in patients with psychotic disorders and HC. These findings may suggest a modulatory role of the thalamus in prediction error signaling.

Thalamic nuclei volumes in schizophrenia and bipolar spectrum disorders - Associations with diagnosis and clinical characteristics.

The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear. We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29years, 59% male), 322 patients with BD (30years, 40% male), and 826 healthy controls (HC) (34years, 54% male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD. Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes. Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.

Functional connectivity between medial pulvinar and cortical networks as a predictor of arousal to noxious stimuli during sleep.

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre-stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans-thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra-cortical and intra-thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre- and post-stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo-cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre-stimulus period. The association between pre-stimulus widespread increase in thalamo-cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans-thalamic transfer of information between cortical areas.

Thalamic Nuclei Volumes in Psychotic Disorders and Youth With Psychosis Spectrum Symptoms

Several influential models posit that the pathophysiology of psychosis includes thalamic association nuclei and that thalamic abnormalities are due, at least in part, to atypical brain development, and related to mechanisms of cognitive impairment. While multiple lines of evidence are consistent with thalamic involvement in psychosis, evidence that association nuclei are differentially affected is sparse.

Brain dynamics: the temporal variability of connectivity, and differences in schizophrenia and ADHD

We describe advances in the understanding of brain dynamics that are important for understanding the operation of the cerebral cortex in health and disease. In data from 1017 participants from the Human Connectome Project, we show that early visual and connected areas have low temporal variability of their functional connectivity. We show that a low temporal variability of the connectivity of cortical areas is related to high mean functional connectivity between those areas, and provide an account of how these dynamics arise. We then investigate how these concepts help to understand brain dynamics in mental disorders. We find that in both first episode and long-term schizophrenia, reduced functional connectivity of early visual and related temporal cortex areas is associated with increased temporal variability of the functional connectivity, consistent with decreased stability of attractor networks related to sensory processing. In ADHD, we find these functional connectivities are increased and their temporal variability is decreased, and relate this to increased engagement with visual sensory input as manifest in high screen time usage in ADHD. We further show that these differences in the dynamics of the cortex in schizophrenia, and ADHD can be related to differences in the functional connectivity of the specific sensory vs. association thalamic nuclei. These discoveries help to advance our understanding of cortical operation in health, and in some mental disorders.

Thalamic Nuclei Volumes in Psychotic Disorders and in Youths With Psychosis Spectrum Symptoms.

Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental cohort, and to determine whether nuclear volumes were associated with cognitive function. Thalamic nuclei volumes were tested in a cross-sectional sample of 472 adults (293 with psychosis) and the Philadelphia Neurodevelopmental Cohort (PNC), consisting of 1,393 youths (398 with psychosis spectrum symptoms and 609 with other psychopathologies), using a recently developed, validated method for segmenting thalamic nuclei and complementary voxel-based morphometry. Cognitive function was measured with the Screen for Cognitive Impairment in Psychiatry in the psychosis cohort and the Penn Computerized Neurocognitive Battery in the PNC. The psychosis group had smaller pulvinar, mediodorsal, and, to a lesser extent, ventrolateral nuclei volumes compared with the healthy control group. Youths with psychosis spectrum symptoms also had smaller pulvinar volumes, compared with both typically developing youths and youths with other psychopathologies. Pulvinar volumes were positively correlated with general cognitive function. The study findings demonstrate that smaller thalamic association nuclei represent a neurodevelopmental abnormality associated with psychosis, risk for psychosis in youths, and cognitive impairment. Identifying specific thalamic nuclei abnormalities in psychosis has implications for early detection of psychosis risk and treatment of cognitive impairment in psychosis.

Thalamic Nuclei Volumes in Psychotic Disorders and Youth With Psychosis Spectrum Symptoms

Several influential models posit that the pathophysiology of psychosis includes thalamic association nuclei and that thalamic abnormalities are due, at least in part, to atypical brain development, and related to mechanisms of cognitive impairment. While multiple lines of evidence are consistent with thalamic involvement in psychosis, evidence that association nuclei are differentially affected is sparse.

Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas.

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto- and chemoarchitectural markers from Nissl-, parvalbumin-and muscarinic acetylcholine receptor M2-staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co-register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico-cortical connections.

Congenital blindness affects diencephalic but not mesencephalic structures in the human brain.

While there is ample evidence that the structure and function of visual cortical areas are affected by early visual deprivation, little is known of how early blindness modifies subcortical relay and association thalamic nuclei, as well as mesencephalic structures. Therefore, in the present multicenter study, we used MRI to measure volume of the superior and inferior colliculi, as well as of the thalamic nuclei relaying sensory and motor information to the neocortex, parcellated according to atlas-based thalamo-cortical connections, in 29 individuals with congenital blindness of peripheral origin (17 M, age 35.7 ± 14.3 years) and 29 sighted subjects (17 M, age 31.9 ± 9.0). Blind participants showed an overall volume reduction in the left (p = 0.008) and right (p = 0.007) thalami, as compared to the sighted individuals. Specifically, the lateral geniculate (i.e., primary visual thalamic relay nucleus) was 40% reduced (left: p = 4 × 10(-6), right: p < 1 × 10(-6)), consistent with findings from animal studies. In addition, associated thalamic nuclei that project to temporal (left: p = 0.005, right: p = 0.005), prefrontal (left: p = 0.010, right: p = 0.014), occipital (left: p = 0.005, right: p = 0.023), and right premotor (p = 0.024) cortical regions were also significantly reduced in the congenitally blind group. Conversely, volumes of the relay nuclei directly involved in auditory, motor, and somatosensory processing were not affected by visual deprivation. In contrast, no difference in volume was observed in either the superior or the inferior colliculus between the two groups. Our findings indicate that visual loss since birth leads to selective volumetric changes within diencephalic, but not mesencephalic, structures. Both changes in reciprocal cortico-thalamic connections or modifications in the intrinsic connectivity between relay and association nuclei of the thalamus may contribute to explain these alterations in thalamic volumes. Sparing of the superior colliculi is in line with their composite, multisensory projections, and with their not exclusive visual nature.

The Subthalamic Nucleus Is One of Multiple Innervation Sites for Long-Range Corticofugal Axons: A Single-Axon Tracing Study in the Rat

The frontal cortex provides strong excitatory inputs to the subthalamic nucleus (STN), and these cortico-STN inputs play critical roles in the control of basal ganglia activity. It has been assumed from anatomical and physiological studies that STN is innervated mainly by collaterals of thick and fast conducting pyramidal tract axons originating from the frontal cortex deep layer V neurons, implying that STN directly receives efferent copies of motor commands. To more closely examine this assumption, we performed biotinylated dextran amine anterograde tracing studies in rats to examine the cortical layer of origin, the sizes of parent axons, and whether or not the cortical axons emit any other collaterals to brain areas other than STN. This study revealed that the cortico-STN projection is formed mostly by collaterals of a small fraction of small-to-medium-sized long-range corticofugal axons, which also emit collaterals that innervate multiple other brain sites including the striatum, associative thalamic nuclei, superior colliculus, zona incerta, pontine nucleus, multiple other brainstem areas, and the spinal cord. The results imply that some layer V neurons are involved in associative control of movement through multiple brain innervation sites and that the cortico-STN projection is one part of this multiple corticofugal system.

VGLUT1 mRNA and protein expression in the visual system of prosimian galagos (Otolemur garnetti)

The presynaptic storage and release of glutamate, an excitatory neurotransmitter, is modulated by a family of transport proteins known as vesicular glutamate transporters. Vesicular glutamate transporter 1 (VGLUT1) is widely distributed in the central nervous system of most mammalian and nonmammalian species, and regulates the uptake of glutamate into synaptic vesicles as well as the transport of filled glutamatergic vesicles to the terminal membrane during excitatory transmission. In rodents, VGLUT1 mRNA is primarily found in the neocortex, cerebellum, and hippocampus, and the VGLUT1 transport protein is involved in intercortical and corticothalamic projections that remain distinct from projections involving other VGLUT isoforms. With the exception of a few thalamic sensory nuclei, VGLUT1 mRNA is absent from subcortical areas and does not colocalize with other VGLUT mRNAs. VGLUT1 is similarly restricted to a few thalamic association nuclei and does not colocalize with other VGLUT proteins. However, recent work in primates has shown that VGLUT1 mRNA is also found in several subcortical nuclei as well as cortical areas, and that VGLUT1 may overlap with other VGLUT isoforms in glutamatergic projections. In order to expand current knowledge of VGLUT1 distributions in primates and gain insight on glutamatergic transmission in the visual system of primate species, we examined VGLUT1 mRNA and protein distributions in the lateral geniculate nucleus, pulvinar complex, superior colliculus, V1, V2, and the middle temporal area (MT) of prosimian galagos. We found that, similar to other studies in primates, VGLUT1 mRNA and protein are widely distributed in both subcortical and cortical areas. However, glutamatergic projections involving VGLUT1 are largely limited to intrinsic connections within subcortical and cortical areas, as well as the expected intercortical and corticothalamic projections. Additionally, VGLUT1 expression in galagos allowed us to identify laminar subdivisions of the superior colliculus, V1, V2, and MT.

Selective reduction of neuron number and volume of the mediodorsal nucleus of the thalamus in macaques following irradiation at early gestational ages.

Neurons in the macaque brain arise from progenitors located near the cerebral ventricles in a temporally segregated manner such that lethal doses of ionizing irradiation, if administered over a discrete time interval, can deplete individual nuclei selectively. A previous study showed that neuron number in the dorsal lateral geniculate nucleus is reduced following early gestational exposure to x-irradiation (Algan and Rakic [1997] J. Comp. Neurol. 12:335-352). Here we examine whether similarly timed irradiation decreases neuron number in three associational thalamic nuclei: mediodorsal (MD), anterior, and pulvinar. Ten macaques were exposed to multiple doses of x-rays (total exposure (175-350 cGy) in early gestation (E33-E42) or midgestation (E70-E90); eight nonirradiated macaques were controls. Only the early-irradiated monkeys, not the midgestationally irradiated animals, exhibited deficits in whole-thalamic neuron (-15%) and glia numbers (-21%) compared with controls. Reduction of neuron number (-26%) and volume (-29%) was particularly pronounced in MD. In contrast, cell number and volume were not significantly decreased in the anterior or pulvinar nuclei following early gestational irradiation. Thus, reduced thalamic neuron number was associated specifically with irradiation in early gestation. Persistence of the thalamic neuronal deficit in adult animals indicates that prenatally deleted neurons had not been replenished during maturation or in adulthood. The selective reduction of MD neuron number also supports the protomap hypothesis that neurons of each thalamic nucleus originate sequentially from separate lines of neuronal stem cells (Rakic [1977a] J. Comp. Neurol. 176:23-52). The early gestationally irradiated macaque is discussed as a potentially useful model for studying the neurodevelopmental pathogenesis of schizophrenia.

Structural abnormalities of the adhesio interthalamica and mediodorsal nuclei of the thalamus in schizophrenia

Objective: Several studies have suggested the existence of thalamic volume reduction in patients with schizophrenia. However, the precise locus of volume reduction within the thalamus has scarcely been investigated. On the other hand, underdevelopment of the adhesio interthalamica [AI; Danos, P., Baumann, B., Kramer, A., Bernstein, H.G., Stauch, R., Krell, D., Falkai, P., Bogerts, B., 2003. Volumes of association thalamic nuclei in schizophrenia: a post-mortem study. Schizophr. Res. 60 141–155], which bridges bilateral medial edges of the thalamus, has been reported in patients with schizophrenia. We assessed the volumes of mediodorsal nuclei (MDN) of thalami, level of AI development, and their interrelationship, in patients with schizophrenia. Method: A sample of 58 patients with schizophrenia and 44 matched healthy volunteers underwent assessment with high-resolution 1-mm-thick anatomical MRI. Volume measurements of the MDN of the thalamus and whole thalamus were performed by manual tracing. The level of AI development was quantitatively defined as the maximal anterior-to-posterior length of the AI. Results: Schizophrenia patients had significantly smaller volumes of bilateral MDN. AI ratings were twice as high in women than in men among the control subjects; however, no gender difference emerged in the schizophrenia group due to reduced ratings in female patients. No significant correlation was found between MDN volumes and AI ratings among both groups. Conclusions: These results provide evidence of volume reduction of the MDN, and female-specific underdevelopment of the AI in schizophrenia. As we did not demonstrate a relationship between MDN volume and AI ratings, it is suggested that these two measures of medial thalamic abnormality are manifestations of different neuropathological processes in schizophrenia patients.

Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus

Vesicular glutamate transporters (VGLUTs) are responsible for glutamate trafficking and for the subsequent regulated release of this excitatory neurotransmitter at the synapse. Three isoforms of the VGLUT have been identified, now known as VGLUT1, VGLUT2, and VGLUT3. Both VGLUT1 and VGLUT2 have been considered definitive markers of glutamatergic neurons, whereas VGLUT3 is expressed in nonglutamatergic neurons such as cholinergic striatal interneurons. It is widely believed that VGLUT1 and VGLUT2 are expressed in a complementary manner at the cortical and thalamic levels, suggesting that these glutamatergic neurons fulfill different physiological functions. In the present work, we analyzed the pattern of VGLUT1 and VGLUT2 mRNA expression at the thalamic level by using single and dual in situ hybridization. In accordance with current beliefs, we found significant expression of VGLUT2 mRNA in all the thalamic nuclei, while moderate expression of VGLUT1 mRNA was consistently found in both the principal relay and the association thalamic nuclei. Interestingly, individual neurons within these nuclei coexpressed both VGLUT1 and VGLUT2 mRNAs, suggesting that these individual thalamic neurons may have different ways of trafficking glutamate. These results call for a reappraisal of the previously held concept regarding the mutually exclusive distribution of VGLUT transporters in the central nervous system.

Differential synaptology of vGluT2‐containing thalamostriatal afferents between the patch and matrix compartments in rats

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents.

Posterior parietal cortex projections to the ventral lateral and some association thalamic nuclei in Macaca mulatta

The study focused on projections from the posterior parietal cortex (PPC) to the ventral lateral thalamic nucleus (VL) and three thalamic association nuclei, mediodorsal (MD), lateral posterior (LP) and pulvinar. For light microscopic analysis small biotinylated dextran amine (BDA) or biocytin injections were placed in midrostral and dorsal portions of the inferior parietal lobule (IPL), respectively. The distribution of anterograde and retrograde labeling was charted, and representative axons and terminal fields were reconstructed in the sagittal plane to examine their features. Two types of fibers were identified—those of thin diameter forming diffuse terminal fields with small boutons, and thick fibers forming focal terminal fields with large boutons. Area PFG injection of BDA resulted in labeling of both types of fibers in LP, MD, and pulvinar, whereas only fibers of the first type were found in VL. Biocytin injection in area Opt resulted in preferential labeling of large fibers terminating in LP and pulvinar. Further electron microscopic analysis of labeled boutons in VL and LP, following a large wheat germ agglutinin conjugated horseradish peroxidase injection in the middle of IPL, confirmed the existence of small and large corticothalamic boutons and their different termination sites: the small boutons formed synapses on distal dendrites while the large boutons were found close to somata of thalamocortical projection neurons, on the dendrites of local circuit neurons and in complex synaptic arrangements, such as glomeruli. The results demonstrate that projections from small loci of the PPC to functionally and connectionally different thalamic nuclei differ anatomically, implying a different functional impact on these diverse targets.

Volumes of association thalamic nuclei in schizophrenia: a postmortem study

The major association thalamic nuclei, the mediodorsal nucleus (MD) and the medial pulvinar nucleus (PUM) are regarded as important parts of the circuits among association cortical regions. Association cortical regions of the frontal, parietal and temporal lobes have been repeatedly implicated in the neuropathology of schizophrenia. Thus, the aim of the present postmortem study was to investigate the volumes of association thalamic nuclei in this disease. The volumes of the whole thalamus (THAL), MD and PUM were measured in each hemisphere of brains of 12 patients with schizophrenia and 13 age-matched and gender-matched normal control subjects without neuropsychiatric disorders. Patients with schizophrenia exhibited significant volume reductions in both the MD and the PUM, the reductions being more pronounced in the PUM. The volume of the PUM in the left (−19.7%, P=0.02) and right (−22.1%, P=0.01) hemispheres was significantly reduced in the schizophrenia group. The volume of the MD was reduced in both hemispheres in the schizophrenia group. However, the volume reduction was only significant in the left hemisphere (−9.3%, P=0.03). Patients with schizophrenia also exhibited a decreased volume of the THAL in the left (−16.4%, P=0.003) and right (−15.2%, P=0.006) hemispheres. There were no significant correlations between thalamic volumes and duration of illness or age of the patients. In conclusion, the present data indicate volume reductions of association thalamic nuclei in schizophrenia. These anatomical findings are consistent with the view that schizophrenia may be associated with disturbances of association cortical networks. However, the findings of a substantial volume reduction of the THAL suggest that the volumes of additional thalamic nuclei may be also reduced in schizophrenia.

Telencephalic origin of human thalamic GABAergic neurons.

In non-primate mammalian species, telencephalic and diencephalic neurons originate from their respective local proliferative zones. Using vital dye labeling in organotypic slice cultures, we show that in human brain, a contingent of neurons from the ganglionic eminence of the telencephalon migrate to the dorsal thalamic association nuclei of the diencephalon. These neurons rely on homotypic-neurophilic guidance during their migration, are GABAergic, and express Dlx1/2 homeodomain-containing proteins. Similar experiments in a non-human primate and in rodent embryos did not reveal a similar migratory pathway. Migration assays demonstrated that the human dorsal thalamus attracts telencephalic cells, an effect not observed in the mouse, in which such migration is inhibited by chemorepulsive cues. These data suggest that modifications in the pattern of migratory guidance cues in the forebrain may underlie the appearance of a new migratory pathway and thus contribute to the evolutionary expansion of the thalamic association nuclei in the human.

Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: light microscopy analysis using an antibody directed against the C-terminus.

Corticotropin-releasing hormone (CRH) receptor type 1 (CRF(1)) is a member of the receptor family mediating the effects of CRH, a critical neuromediator of stress-related endocrine, autonomic, and behavioral responses. The detailed organization and fine localization of CRF(1)-like immunoreactivity (CRF(1)-LI) containing neurons in the rodent have not been described, and is important to better define the functions of this receptor. Here we characterize in detail the neuroanatomical distribution of CRF(1)-immunoreactive (CRF(1)-ir) neurons in the mouse brain, using an antiserum directed against the C-terminus of the receptor. We show that CRF(1)-LI is abundantly yet selectively expressed, and its localization generally overlaps the target regions of CRH-expressing projections and the established distribution of CRF(1) mRNA, with several intriguing exceptions. The most intensely CRF(1)-LI-labeled neurons are found in discrete neuronal systems, i.e., hypothalamic nuclei (paraventricular, supraoptic, and arcuate), major cholinergic and monoaminergic cell groups, and specific sensory relay and association thalamic nuclei. Pyramidal neurons in neocortex and magnocellular cells in basal amygdaloid nucleus are also intensely CRF(1)-ir. Finally, intense CRF(1)-LI is evident in brainstem auditory associated nuclei and several cranial nerves nuclei, as well as in cerebellar Purkinje cells. In addition to their regional specificity, CRF(1)-LI-labeled neurons are characterized by discrete patterns of the intracellular distribution of the immunoreaction product. While generally membrane associated, CRF(1)-LI may be classified as granular, punctate, or homogenous deposits, consistent with differential membrane localization. The selective distribution and morphological diversity of CRF(1)-ir neurons suggest that CRF(1) may mediate distinct functions in different regions of the mouse brain.

Corticothalamic projections from layer 5 of the vibrissal barrel cortex in the rat

This study bears on the projections of layer 5 cells of the vibrissal sensory cortex to the somatosensory thalamus in rats. Small groups of cells were labeled with biotinylated dextran amine (BDA), and their axonal arborizations were individually reconstructed from horizontal sections counterstained for cytochrome oxidase. Results show that the vast majority ( approximately 95%) of layer 5 axons that innervate the somatosensory thalamus are collaterals of corticofugal fibers that project to the brainstem. The anterior pretectal nucleus, the deep layers of the superior colliculus, and the pontine nuclei are among the structures most often coinnervated. In the thalamus, layer 5 axons terminate exclusively in the dorsal part of the posterior group (Po), where they form clusters of large terminations. Because dorsal Po projects to multiple cortical areas, we sought to determine whether all recipient areas return a layer 5 projection to this part of the thalamus. Additional experiments using fluoro-gold and BDA injections provided evidence that the primary somatosensory area is the sole source of layer 5 projections to dorsal Po but that this thalamic region receives convergent layer 6 projections from the primary and second somatosensory areas and from the motor and insular cortices. These results show that layer 5 projections do not overlap in associative thalamic nuclei, thus defining area-related subdivisions. Furthermore, the coinnervation of brainstem nuclei by layer 5 CT axons suggests that this pathway conveys to the thalamus a copy of the cortical output aimed at brainstem structures.