Layer 5 of cortex innervates the thalamic reticular nucleus in mice.

Neurons in the thalamic reticular nucleus (TRN) are a primary source of inhibition to the dorsal thalamus and, as they are innervated in part by the cortex, are a means of corticothalamic regulation. Previously, cortical inputs to the TRN were thought to originate solely from layer 6 (L6), but we recently reported the presence of putative synaptic terminals from layer 5 (L5) neurons in multiple cortical areas in the TRN [J. A. Prasad, B. J. Carroll, S. M. Sherman, J. Neurosci. 40, 5785-5796 (2020)]. Here, we demonstrate with electron microscopy that L5 terminals from multiple cortical regions make bona fide synapses in the TRN. We further use light microscopy to localize these synapses relative to recently described TRN subdivisions and show that L5 terminals target the edges of the somatosensory TRN, where neurons reciprocally connect to higher-order thalamus, and that L5 terminals are scarce in the core of the TRN, where neurons reciprocally connect to first-order thalamus. In contrast, L6 terminals densely innervate both edge and core subregions and are smaller than those from L5. These data suggest that a sparse but potent input from L5 neurons of multiple cortical regions to the TRN may yield transreticular inhibition targeted to higher-order thalamus.

Structural plasticity of GABAergic and glutamatergic networks in the motor thalamus of parkinsonian monkeys.

In the primate thalamus, the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM) receive GABAergic projections from the internal globus pallidus (GPi) and glutamatergic inputs from motor cortices. In this study, we used electron microscopy to assess potential structural changes in GABAergic and glutamatergic microcircuits in the VApc and CM of MPTP-treated parkinsonian monkeys. The intensity of immunostaining for GABAergic markers in VApc and CM did not differ between control and parkinsonian monkeys. In the electron microscope, three major types of terminals were identified in both nuclei: (a) vesicular glutamate transporter 1 (vGluT1)-positive terminals forming asymmetric synapses (type As), which originate from the cerebral cortex, (b) GABAergic terminals forming single symmetric synapses (type S1), which likely arise from the reticular nucleus and GABAergic interneurons, and (c) GABAergic terminals forming multiple symmetric synapses (type S2), which originate from GPi. The density of As terminals outnumbered that of S1 and S2 terminals in VApc and CM of control and parkinsonian animals. No significant change was found in the abundance and synaptic connectivity of S1 and S2 terminals in VApc or CM of MPTP-treated monkeys, while the prevalence of "As" terminals in VApc of parkinsonian monkeys was 51.4% lower than in controls. The cross-sectional area of vGluT1-positive boutons in both VApc and CM of parkinsonian monkeys was significantly larger than in controls, but their pattern of innervation of thalamic cells was not altered. Our findings suggest that the corticothalamic system undergoes significant synaptic remodeling in the parkinsonian state.

A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus.

BACKGROUND: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. OBJECTIVES: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. STUDY DESIGN: This study used an experimental design in rats. SETTING: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). RESULTS: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. LIMITATIONS: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions. KEY WORDS: Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.

Tooth pulp injury induces sex-dependent neuronal reshaping in the ventral posterolateral nucleus of the rat thalamus.

Orofacial injuries often result in persistent pain and are therefore considered a common health problem worldwide. Considerable evidence suggests that peripheral sensory nerve injury results in diverse plastic changes in the central nervous system (CNS). Tooth pulp is innervated by trigeminal afferents which extend to the trigeminal brainstem sensory nuclear complex and send input to higher level neurons in the CNS, including the ventral posterolateral nucleus of the thalamus (VPL). In the present study, we examined the long term effects of pulpal injury on neuronal arborization in the VPL using morphological analysis via Golgi-Cox staining. In addition, we examined these effects in both male and female rats due to the major prevalence of oral pain in women. Quantitative morphological analysis revealed that pulpal injury induced neuronal hypertrophy in VPL neurons of female rats. In clear contrast, pulpal injury increased arborization close to the soma and reduced arborization distal to the soma without modification of total dendritic length in male rats. As a result, we show, for the first time, sex-dependent morphological alterations in VPL neurons after orofacial peripheral injury. Since dental injuries are readily reproducible in rat dental molars and closely mimic the clinical setting in humans, this model represents a useful tool to further understand mechanisms of orofacial pain.

Quantitative 3D Ultrastructure of Thalamocortical Synapses from the "Lemniscal" Ventral Posteromedial Nucleus in Mouse Barrel Cortex.

Thalamocortical synapses from "lemniscal" neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2-4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 µm3), and contain 1-3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses.

Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys.

T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson's disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70-80 % of the Cav3.1-immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non-glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus.

Synaptic changes in GABAA receptor expression in the thalamus of the stargazer mouse model of absence epilepsy.

Absence seizures are known to result from disturbances within the cortico-thalamocortical network, which remains partially synchronous under normal conditions but switches to a state of hypersynchronicity and hyperexcitability during absence seizures. There is evidence to suggest that impaired GABAergic inhibitory function within the thalamus could contribute to the generation of hypersynchronous oscillations in some animal models of absence epilepsy. Recently, we demonstrated region-specific alterations in the tissue expression level of GABAA receptors (GABA(A)Rs) α1 and ß2 subunits within the thalamus of the stargazer mouse model of absence epilepsy. In the present study we investigated whether changes in these subunits also occur at synapses in the ventral posterior (VP) complex where they are components of phasic GABA(A)R receptors. Postembedding immunogold cytochemistry and electron microscopy were used to analyze the relative synaptic expression of α1 and ß2 subunits in the VP thalamic region in epileptic stargazer mice compared to their non-epileptic littermates. We show that there is a significant increase in expression of α1 and ß2 subunits (53.6% and 45.8%, respectively) at synapses in the VP region of stargazers, indicative of an increase in phasic GABA(A)Rs at thalamocortical (TC) relay neurons. Furthermore, we investigated whether tissue expression of GABA(A)R subunits α4 and δ, which constitute part of tonic GABA(A)Rs in the VP region, is altered in the stargazer mouse. Semi-quantitative Western blotting showed a significant increase in GABA(A)R α4 and δ subunits in the VP region of stargazer thalamus, which would indicate an increase in tonic GABA(A)R expression. Our findings show that there are changes in the levels of both phasic and tonic GABA(A)Rs in the VP thalamus; altered GABAergic inhibition within the VP could be one of many mechanisms contributing to the generation of absence seizures in this model.

Early Exposure to General Anesthesia with Isoflurane Downregulates Inhibitory Synaptic Neurotransmission in the Rat Thalamus.

Recent evidence supports the idea that common general anesthetics (GAs) such as isoflurane (Iso) and nitrous oxide (N2O; laughing gas) are neurotoxic and may harm the developing mammalian brain, including the thalamus; however, to date very little is known about how developmental exposure to GAs may affect synaptic transmission in the thalamus which, in turn, controls the function of thalamocortical circuitry. To address this issue we used in vitro patch-clamp recordings of evoked inhibitory postsynaptic currents (eIPSCs) from intact neurons of the nucleus reticularis thalami (nRT) in brain slices from rat pups (postnatal age P10-P18) exposed at age of P7 to clinically relevant GA combinations of Iso and N2O. We found that rats exposed to a combination of 0.75 % Iso and 75 % N2O display lasting reduction in the amplitude and faster decays of eIPSCs. Exposure to sub-anesthetic concentrations of 75 % N2O alone or 0.75 % Iso alone at P7 did not affect the amplitude of eIPSCs; however, Iso alone, but not N2O, significantly accelerated decay of eIPSCs. Anesthesia with 1.5 % Iso alone decreased amplitudes, caused faster decay and decreased the paired-pulse ratio of eIPSCs. We conclude that anesthesia at P7 with Iso alone or in combination with N2O causes plasticity of eIPSCs in nRT neurons by both presynaptic and postsynaptic mechanisms. We hypothesize that changes in inhibitory synaptic transmission in the thalamus induced by GAs may contribute to altered neuronal excitability and consequently abnormal thalamocortical oscillations later in life.

[Neuronal populations: sources of the corticothalamic projections to the partially deafferented ventrolateral thalamic nucleus].

The features of distribution and morphological structure of the motor cortex neuronal populations projecting to the cerebellar-recipient ventrolateral nucleus of the thalamus after its partial deafferentation were studied in adult cats. The partial deafferentation of the ventrolateral nucleus was evoked by preliminary (three months) electrolytic destruction of the contralateral interpositus nucleus of the cerebellum. The method of retrograde axonal transport with local introductions of the marker was used. All labeled neurons were presented by populations of non-pyramidal neurons and small and medium-sized pyramids, which were distributed in the deep cortical layers: in a lower layer division of V and mostly in layer VI. The labeled neurons were observed in cortical fields 4γ and field 6αß. The data obtained showed no structural reorganization of cortical projections to the deafferented ventrolateral nucleus of the thalamus. It is assumed that this is due to the high degree of specialization of the studied system, triggering the motor program. Neuroplastic changes manifested in the abnormal transformation of proximal portions of dendrites and presence of a large number of "paired" pyramidal neurons compared to intact animals.

Vesicular glutamate transporters define two sets of glutamatergic afferents to the somatosensory thalamus and two thalamocortical projections in the mouse.

The ventral posterior nucleus of the thalamus (VP) receives two major sets of excitatory inputs, one from the ascending somatosensory pathways originating in the dorsal horn, dorsal column nuclei, and trigeminal nuclei, and the other originating from the cerebral cortex. Both systems use glutamate as neurotransmitter, as do the thalamocortical axons relaying somatosensory information from the VP to the primary somatosensory cortex (SI). The synapses formed by these projection systems differ anatomically, physiologically, and in their capacity for short-term synaptic plasticity. Glutamate uptake into synaptic vesicles and its release at central synapses depend on two isoforms of vesicular glutamate transporters, VGluT1 and VGluT2. Despite ample evidence of their complementary distribution, some instances exist of co-localization in the same brain areas or at the same synapses. In the thalamus, the two transcripts coexist in cells of the VP and other nuclei but not in the posterior or intralaminar nuclei. We show that the two isoforms are completely segregated at VP synapses, despite their widespread expression throughout the dorsal and ventral thalamus. We present immunocytochemical, ultrastructural, gene expression, and connectional evidence that VGluT1 in the VP is only found at corticothalamic synapses, whereas VGluT2 is only found at terminals made by axons originating in the spinal cord and brainstem. By contrast, the two VGluT isoforms are co-localized in thalamocortical axon terminals targeting layer IV, but not in those targeting layer I, suggesting the presence of two distinct projection systems related to the core/matrix pattern of organization of thalamocortical connectivity described in other mammals.

Prefrontal projections to the thalamic reticular nucleus form a unique circuit for attentional mechanisms.

The inhibitory thalamic reticular nucleus (TRN) intercepts and modulates all corticothalamic and thalamocortical communications. Previous studies showed that projections from sensory and motor cortices originate in layer VI and terminate as small boutons in central and caudal TRN. Here we show that prefrontal projections to TRN in rhesus monkeys have a different topographic organization and mode of termination. Prefrontal cortices projected mainly to the anterior TRN, at sites connected with the mediodorsal, ventral anterior, and anterior medial thalamic nuclei. However, projections from areas 46, 13, and 9 terminated widely in TRN and colocalized caudally with projections from temporal auditory, visual, and polymodal association cortices. Population analysis and serial EM reconstruction revealed two distinct classes of corticoreticular terminals synapsing with GABA/parvalbumin-positive dendritic shafts of TRN neurons. Most labeled boutons from prefrontal axons were small, but a second class of large boutons was also prominent. This is in contrast to the homogeneous small TRN terminations from sensory cortices noted previously and in the present study, which are thought to arise exclusively from layer VI. The two bouton types were often observed on the same axon, suggesting that both prefrontal layers V and VI could project to TRN. The dual mode of termination suggests a more complex role of prefrontal input in the functional regulation of TRN and gating of thalamic output back to the cortex. The targeting of sensory tiers of TRN by specific prefrontal areas may underlie attentional regulation for the selection of relevant sensory signals and suppression of distractors.

The differential distribution of the growth-associated protein-43 in first and higher order thalamic nuclei of the adult rat.

Corticothalamic axons from layer 5 of primary and secondary auditory and visual areas have large terminals that make multiple synaptic contacts on proximal dendrites of relay cells in higher order thalamic nuclei and have been termed "driver" inputs. The corticothalamic cells express mRNA for the presynaptic growth-associated protein-43, in the adult rat [Feig SL (2004) Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP-43 mRNA in the adult rat. J Comp Neurol 468:96-111]. In contrast, ascending driver afferents to first order nuclei (e.g. retinal, inferior collicular, and lemniscal) lose growth-associated protein-43 as mature synaptic terminals are established. Levels of immunoreactivity for growth-associated protein-43 are compared for first and higher order visual (lateral geniculate and lateral posterior), auditory (ventral and dorsal divisions of the medial geniculate), and somatosensory (ventral posterior and posterior) thalamic nuclei. At one week postnatal, staining for growth-associated protein-43 is uniform throughout first and higher order thalamic nuclei. By three weeks and thereafter, staining is denser in the higher order than first order thalamic nuclei. Electron microscopy shows growth-associated protein-43 in profiles with characteristics of afferents from layer 5 in LP and medial geniculate nucleus and no such label in retinal afferents in lateral geniculate nucleus. In these nuclei, approximately 25% of the profiles with characteristics of cortical afferents from layer 6 have label for growth-associated protein-43. The superficial layers of the superior colliculus also show growth-associated protein-43 positive profiles with characteristics of terminals from cortical layer 5. Some growth-associated protein-43 positive terminals were also positive for GABA in the thalamic nuclei studied and in the superior colliculus. The data suggest that sensory afferents to first order thalamocortical relays become stabilized once mature synaptic patterns are established, but the higher stages of information processing involving higher order thalamic relays, via cells in cortical layer 5, retain plasticity related to growth-associated protein-43 in the adult.

Rat trigeminal lamina I neurons that project to thalamic or parabrachial nuclei contain the mu-opioid receptor.

Ligands of the mu-opioid receptor are known to inhibit nociceptive transmission in the dorsal horn, yet the cellular site(s) of action for this inhibition remain to be fully elucidated. Neurons located in lamina I of the dorsal horn are involved in distinct aspects of nociceptive transmission. Neurons projecting to the thalamus are thought to be involved in sensory-discriminative aspects of pain perception, while neurons projecting to the parabrachial nucleus are thought to be important for emotional and/or autonomic responses to noxious stimuli. The present study examined these two populations of lamina I projection neurons in the trigeminal dorsal horn to determine if the mu-opioid receptor protein (MOR1) is differentially located in these populations of neurons. Lamina I projection neurons were identified using the retrograde tracer FluoroGold (FGold). FGold was injected into either the contralateral thalamus (ventral posterolateral (VPM)/ventral posterolateral (VPL) thalamic region) or into the ipsilateral parabrachial nuclei. The distribution of MOR1 in these neurons was determined using immunocytochemistry. The distribution of MOR1-ir within these two populations of lamina I projection neurons was examined by both confocal and electron microscopy. We found that both populations of projection neurons contained MOR1. Immunogold analyses revealed the presence of MOR1-ir at membrane sites and within the cytoplasm of these neurons. Cytoplasmic receptor labeling may represent sites of synthesis, recycling or reserve populations of receptors. MOR1 was primarily found in the somata and proximal dendrites of projection neurons. In addition, these neurons rarely received synaptic input from MOR1-containing axon terminals. These results indicate that lamina I neurons in trigeminal dorsal horn that project to the thalamic and parabrachial nuclei contain MOR1 and are likely sites of action for MOR ligands that modulate sensory and/or autonomic aspects of pain transmission in the trigeminal dorsal horn.

Degeneration of cholecystokinin-immunoreactive afferents to the VPL thalamus in a mouse model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a progressive neurological disorder of lipid metabolism. The Balb/C npc1 mutant strain is a genetically authentic murine model of NPC, which reproduce the clinical and histologic features of human NP-C. In the present study, we show that cholecystokinin (CCK)-immunoreactive fibers in the thalamic VPL nuclei, which are densely distributed in controls, degenerate in NPC mice. This degeneration is associated with the appearance of CCK-immunoreactive axonal spheroids containing characteristic intracellular inclusions of NP-C. These observations provide supportive evidence of the occurrence of dying-back axonopathy of neurons in the dorsal column nuclei in this mouse model.

Dendroarchitecture and lateral inhibition in thalamic barreloids.

Thalamic cells that relay vibrissa information to barrel cortex are clustered within whisker-related modules termed barreloids. Each barreloid receives input from one principal whisker and inhibitory inputs from reticular thalamic neurons with receptive fields that correspond to that same whisker. Although the proximal dendrites of relay cells are confined to their home barreloid, distal dendrites often extend into surrounding barreloids representing adjacent whiskers on the mystacial pad. It was proposed that this arrangement provides a substrate for a mechanism of lateral inhibition that operates remotely on extrabarreloid dendrites. In the present study, we identified adjacent whiskers that suppressed activity below background levels in barreloid cells, and we used a double-labeling protocol to relate the efficacy of inhibition to the dendroarchitecture of the cells. Significant suppression of background discharges was produced by 92% of adjacent whiskers within rows, by 48% of adjacent whiskers within arcs, but was never observed after deflection of nonadjacent whiskers. The magnitude of lateral inhibition increases linearly as the cumulated length of dendrites increases in the barreloid representing an adjacent whisker (R2 = 0.86; p < 0.0001). As distance between cell bodies and the border of an adjacent barreloid increases, dendritic length in that adjacent barreloid diminishes and so does inhibition. Considering time differences between the arrival of principal and adjacent whisker inputs in barreloids, our data suggest that inhibition operating distally on dendrites acts as a spatial filter that primarily suppresses adjacent whisker inputs and so contributes to enhance edge detection.

Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque.

We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 microm, mean width = 1.29 microm) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 microm). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.

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.

[Neuronal organization of human ventral anterior and ventral lateral thalamic nuclei]. / Neironnaia organizatsiia ventral'nogo perednego i ventral'nogo lateral'nogo iader talamusa cheloveka.

Neuronal composition was studied in two human thalamic nuclei--nucleus ventralis anterior and nucleus ventralis lateralis using serial horizontal and frontal sections stained using Kluver-Barrera and Golgi silver impregnation methods. It was found that the number of neuronal types, composing the nuclei (equal to eight) is greater than previously reported. Proposed neuronal classification based on the characteristics of their processes, in comparison with a similar study performed in dogs (pups) permitted to distinguish two types of neurons--long-axon and short-axon. Long-axon neurons are subdivided into sparsely-branched (reticular and short-dendritic) and densely-branched (arborescent, giant and medium bush-like, penicillar varieties). Short-axon neuronal type includes smooth-dendritic and "shaggy" cells.

Branching-pattern analysis of the dendritic arborization in the thalamic nuclei of the rat brain.

We investigated the dendritic patterns of rapid Golgi-impregnated, highly similar multipolar neurons from two functionally different thalamic regions of the rat brain: two dorsal nuclei (the nucleus laterodorsalis thalami, pars dorsomedialis and the nucleus laterodorsalis thalami, pars ventrolateralis), and two ventral nuclei (the nucleus ventrolateralis thalami and the nucleus ventromedialis thalami). The analysis involved conventional morphometric parameters (height and size) and a new parameter derived from graph theory, the relative imbalance (RI), derived from the branching patterns of the dendrites, which permits quantitative characterization of the dendritic arborization of a neuron. On this basis, neurons can be grouped into three fundamentally different types: type A, or highly-polarized (imbalanced) neurons (RI values close to 1); type B, or medium-polarized neurons (RI values around 0.5); and type C, or balanced neurons with low polarization (RI values close to 0). The orientations of the dendritic arbor, and thus the receptive fields, of the dorsal and ventral thalamic neurons, were mutually perpendicular. The H and S values indicated that the neurons in the dorsal and ventral thalamic nuclei differed significantly. However, their RI values demonstrated that they were similar neurons of type B. Our data reveal that 1 ) the dendritic arbor cannot be reliably characterized purely on the basis of height and size, and 2) RI is a valuable morphometric parameter that identifies the true nature of the dendritic arborization.

Synaptic patterns of thalamocortical afferents in mouse barrels at postnatal day 11.

This study focuses on the synaptic output patterns of thalamocortical axons in mouse barrel cortex at postnatal day (P) 11. Axons were labeled by biotinylated dextran amine transported anterogradely following injection in vivo into the ventrobasal thalamus. Labeled axons in the posteromedial barrel subfield were examined by light and electron microscopy and then reconstructed in three dimensions to assess the spatial distribution of their synapses. Thalamocortical axons form asymmetrical synapses, both at varicosities and along cylindrical portions of the axons; usually, only one synapse occurs per site, contrasting with the case in the adult, in which multiple synapses are typical. At P11, varicosities without synapses are common. As in adult barrels, approximately 80% of synapses formed by thalamocortical axons are with dendritic spines; 20% are with dendritic shafts. The similarity in the distribution of thalamocortical synapses onto spines vs. dendrites in developing and mature barrels indicates that adult synaptic patterns already are specified at a very early stage of thalamocortical synaptogenesis.