Laterodorsal Thalamic Nucleus Research Articles

Thalamic nuclei volume partially mediates the effects of aerobic capacity on fatigue in people with multiple sclerosis.

Fatigue is frequent in people with multiple sclerosis (pwMS) impacting physical and cognitive functions. Lower aerobic capacity and regional thalamic volume may be involved in the pathophysiology of fatigue in pwMS. To identify associations between thalamic nuclei volumes, aerobic capacity and fatigue and to investigate whether the influence of aerobic capacity on fatigue in pwMS is mediated by thalamic integrity. Eighty-three pwMS underwent a clinical evaluation with assessment of fatigue (Modified Fatigue Impact Scale [MFIS]), including physical (pMFIS) and cognitive (cMFIS) components, and peak of oxygen uptake (VO2peak). PwMS and 63 sex- and age-matched healthy controls (HC) underwent a 3T brain MRI to quantify volume of the whole thalamus and its nuclei. Compared to HC, pwMS showed higher global MFIS, pMFIS and cMFIS scores, and lower VO2peak and thalamic volumes (p < 0.001). In pwMS, higher VO2peak was significantly associated with lower MFIS and pMFIS scores (r value = - 0.326 and - 0.356; pFDR ≤ 0.046) and higher laterodorsal thalamic nucleus (Dor) cluster volume (r value = 0.300; pFDR = 0.047). Moreover, lower Dor thalamic cluster volume was significantly associated with higher MFIS, pMFIS and cMFIS scores (r value range = - 0.305; - 0.293; pFDR ≤ 0.049). The volume of Dor thalamic cluster partially mediated the positive effects of VO2peak on both MFIS and cMFIS, with relative indirect effects of 21% and 32% respectively. No mediation was found for pMFIS. Higher VO2peak is associated with lower fatigue in pwMS, likely acting on Dor thalamic cluster volume integrity. Such an effect might be different according to the type of fatigue (cognitive or physical).

Early Detection of Alzheimer's Disease in Postmenopausal Women Using Thalamic Subnuclear Volumetry.

Alzheimer's disease (AD) and aging are intrinsically interconnected with each other and are mediated by molecular, cellular, and biological systems. In particular, a specific pattern of brain volume atrophy is the most profound risk factor for cognitive impairment, including AD, that is directly linked to aging. Thus, this study aimed to investigate knowledge on the early detection of AD in postmenopausal women, focusing on the volume changes of the subcortical regions, including the thalamic subnuclei, in women with AD vs. postmenopausal women. Twenty-one women with AD and twenty-one postmenopausal women without AD underwent magnetic resonance imaging (MRI). Women with AD showed significantly reduced volumes in the hippocampus, thalamus, and amygdala compared with postmenopausal women (p < 0.05, FWE-corrected). After adjustments for age, the right hippocampal volume was found to be significantly lower in the women with AD, but the volumes of the thalamus and amygdala were relatively unaffected. The women with AD exhibited significantly reduced volume in the right laterodorsal nucleus of the thalamus compared with the postmenopausal women (p < 0.05, Bonferroni-corrected). Our findings suggest that the reduced volume of both the right laterodorsal thalamic nucleus and right hippocampus may serve as a potential biomarker for the early detection of AD in postmenopausal women.

Modular microcircuit organization of the presubicular head-direction map.

Our internal sense of direction is thought to rely on the activity of head-direction (HD) neurons. We find that the mouse dorsal presubiculum (PreS), a key structure in the cortical representation of HD, displays a modular "patch-matrix" organization, which is conserved across species (including human). Calbindin-positive layer 2 neurons within the "matrix" form modular recurrent microcircuits, while inputs from the anterodorsal and laterodorsal thalamic nuclei are non-overlapping and target the "patch" and "matrix" compartments, respectively. The apical dendrites of identified HD cells are largely restricted within the "matrix," pointing to a non-random sampling of patterned inputs and to a precise structure-function architecture. Optogenetic perturbation of modular recurrent microcircuits results in a drastic tonic suppression of firing only in a subpopulation of HD neurons. Altogether, our data reveal a modular microcircuit organization of the PreS HD map and point to the existence of cell-type-specific microcircuits that support the cortical HD representation.

A Highly Stable Two-Photon Ratiometric Fluorescence Probe for Real-Time Biosensing and Imaging of Nitric Oxide in Brain Tissues and Larval Zebrafish

A Highly Stable Two-Photon Ratiometric Fluorescence Probe for Real-Time Biosensing and Imaging of Nitric Oxide in Brain Tissues and Larval Zebrafish

The effect of GABAergic neurotransmission on the seizure-related activity of the laterodorsal thalamic nuclei and the somatosensory cortex in a genetic model of absence epilepsy

The present study aimed to investigate the alterations of the GABAergic system in the laterodorsal nucleus (LDN) of the thalamus and the somatosensory cortex (SC) in an experimental model of absence seizure. The effects of pharmacological manipulation of both GABAA and GABAB receptor subunits in the LDN on the generation of spike-wave discharges (SWD) were evaluated. The experiments were carried out in four groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. The expressions of various GABA receptor subunits were studied in the LDN and SC. Furthermore, recordings of unit activity from the LDN and electrocorticography were simultaneously monitored before, during, and after the application of GABAA and GABAB antagonists in the LDN. The generation of SWD in the older WAG/Rij rats was associated with significant alterations in the expression of GABAARα1, GABAARβ3, and GABABR2 subunits in the LDN as well as GABAARα1, GABAARβ3, GABAARγ2, and GABABR2 subunits in the SC. Furthermore, the occurrence of SWD was associated with a significant reduction of gene expression of GABAARα1 and increase of GABAARβ3 in the LDN as well as reduction of GABAARα1, GABAARβ3, GABAARγ2, and GABABR2 in the SC. The microionthophoretic application of the GABAA antagonist bicuculline resulted in a significant increase in the population firing rate of LDN neurons as well as the mean number and duration of SWD. The application of the GABAB antagonist CGP35348 significantly increased the population firing rate of LDN neurons but decreased the mean number of SWD. Our data indicate the regulatory effect of the GABAergic system of the LDN and SC in absence seizures.

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion.

The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM at each PLD compared to pre-lesion status were performed. After lesion, augmented metabolic activation by GVS was detected in cerebellum, mainly contralateral, and in contralateral subcortical structures such as superior colliculus, while diminished activation was observed in ipsilateral visual, entorhinal, and somatosensory cortices, indicating compensatory processes in the non-affected sensory systems of the unlesioned side. The changes in rCGM observed after lesion resembled alterations observed in patients suffering from unilateral thalamic infarction and may be interpreted as brain plasticity mechanisms associated with vestibular compensation and substitution. The second set of experiments aimed at the connections between cortical and subcortical vestibular regions and their neurotransmitter systems. Neuronal tracers were injected in regions processing vestibular and somatosensory information. Injections into the anterior cingulate cortex (ACC) or the primary somatosensory cortex (S1) retrogradely labeled neuronal somata in ventral posteromedial (VPM), posterolateral (VPL), ventrolateral (VL), posterior (Po), and laterodorsal nucleus, dorsomedial part (LDDM), locus coeruleus, and contralateral S1 area. Injections into the parafascicular nucleus (PaF), VPM/VPL, or LDDM anterogradely labeled terminal fields in S1, ACC, insular cortex, hippocampal CA1 region, and amygdala. Immunohistochemistry showed tracer-labeled terminal fields contacting cortical neurons expressing the μ-opioid receptor. Antibodies to tyrosine hydroxylase, serotonin, substance P, or neuronal nitric oxide-synthase did not label any of the traced structures. These findings provide evidence for opioidergic transmission in thalamo-cortical transduction.

From Point A to Point B, and What it Means for Epilepsy.

A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice Bohne P, Schwarz MK, Herlitze S, Mark MD. Front Neural Circuits. 2019;13:51. doi:10.3389/fncir.2019.00051. eCollection 2019.The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior, and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar–hippocampal connections in the mouse brain using combinations of recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC), and thalamic and cerebellar areas, whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP displayed eGFP positive cells in the RC and subiculum (S). To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC, and S, which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial, interposed (IntP), and lateral nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar–hippocampal connection via the laterodorsal and ventrolateral thalamus to RSC, RC, and S. These results strengthen the notion of the cerebellum’s involvement in cognitive functions such as spatial navigation via a polysynaptic circuitry. Anatomical and Physiological Foundations of Cerebello-Hippocampal Interaction Watson TC, Obiang P, Torres-Herraez A, et al. Elife. 2019;8:pii: e41896. doi:10.7554/eLife.41896.Multiple lines of evidence suggest that functionally intact cerebello–hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the 2 structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6 to 12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.

A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice.

The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar-hippocampal connections in the mouse brain using combinations of Recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC) as well as thalamic and cerebellar areas. Whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP, displayed eGFP positive cells in the rhinal cortex and subiculum. To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC and subiculum (S), which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial (FN), interposed (IntP) and lateral (Lat) nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar-hippocampal connection via the laterodorsal and ventrolateral thalamus to RSC, RC and S. These results strengthen the notion of the cerebellum’s involvement in cognitive functions such as spatial navigation via a polysynaptic circuitry.

Considering the Evidence for Anterior and Laterodorsal Thalamic Nuclei as Higher Order Relays to Cortex.

Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal system and medial temporal lobes are key brain regions. In addition, severe amnesia also occurs after damage or dysfunction to the anterior thalamic nuclei; this subcortical thalamic hub is interconnected to these key cortical memory structures. Behavioral, anatomical, and physiological evidence across mammalian species has shown that interactions between the anterior thalamic nuclei, cortex and hippocampal formation are vital for spatial memory processing. Furthermore, the adjacent laterodorsal thalamic nucleus (LD), interconnected to the retrosplenial cortex (RSC) and visual system, also contributes to spatial memory in mammals. However, how these thalamic nuclei contribute to memory still remains largely unknown. Fortunately, our understanding of the importance of the thalamus in cognitive processes is being redefined, as widespread evidence challenges the established view of the thalamus as a passive relay of sensory and subcortical information to the cortex. In this review article, we examine whether the anterior thalamic nuclei and the adjacent LD are suitable candidates for “higher-order” thalamic nuclei, as defined by the Sherman and Guillery model. Rather than simply relaying information to cortex, “higher-order” thalamic nuclei have a prominent role in cognition, as they can regulate how areas of the cortex interact with one another. These considerations along with a review of the latest research will be used to suggest future studies that will clarify the contributions that the anterior and LD have in supporting cortical functions during cognitive processes.

CREB down-regulation in the laterodorsal thalamic nucleus deteriorates memory consolidation in rats.

The laterodorsal thalamic nucleus (LD) is believed to play roles in learning and memory, especially spatial tasks. However, the molecular mechanism that underlies the cognitive process in the LD remains unclear and needs to be investigated. So far, there is plenty of evidence indicating that plasticity has been in some of the cortical or subcortical regions closely related to the LD, particularly stimulated by external learning tasks. Therefore, the present study aimed to test the hypothesis that similar effect exists in the LD. The transcription factor, cAMP-response element binding protein (CREB), works essentially in brain plasticity by tightly regulating the transcriptional level of memory-related target genes, and the increase of activated CREB (phosphorylated CREB, p-CREB) could facilitate memory consolidation. In this study, the siRNA against CREB was synthesized to down-regulate the CREB mRNA in the LD. After Morris water maze behavioral training, CREB siRNA rats exhibited a memory deficiency, significantly diverging from the control groups. In subsequent detection, the expression of p-CREB of these memory impairment rats attenuated. These results support the hypothesis that CREB-mediated plasticity contributes to memory facilitation and consolidation in the LD.

Trajectory of hippocampal fibres to the contralateral anterior thalamus and mammillary bodies in rats, mice, and macaque monkeys.

The routes by which the hippocampal formation projects bilaterally to the anterior thalamic nuclei and mammillary bodies were examined in the mouse, rat, and macaque monkey. Despite using different methods and different species, the principal pattern remained the same. For both target areas, the contralateral hippocampal (subiculum) projections arose via efferents in the postcommissural fornix ipsilateral to the tracer injection, which then crossed hemispheres both in or just prior to reaching the target site within the thalamus or hypothalamus. Precommissural fornix fibres could not be followed to the target areas. There was scant evidence that the ventral hippocampal commissure or decussating fornix fibres contribute to these crossed subiculum projections. Meanwhile, a small minority of postsubiculum projections in the mouse were seen to cross in the descending fornix at the level of the caudal septum to join the contralateral postcommissural fornix before reaching the anterior thalamus and lateral mammillary nucleus on that side. Although the rodent anterior thalamic nuclei also receive nonfornical inputs from the subiculum and postsubiculum via the ipsilateral internal capsule, few, if any, of these projections cross the midline. It was also apparent that nuclei within the head direction system (anterodorsal thalamic nucleus, laterodorsal thalamic nucleus, and lateral mammillary nucleus) receive far fewer crossed hippocampal inputs than the other anterior thalamic or mammillary nuclei. The present findings increase our understanding of the fornix and its component pathways while also informing disconnection analyses involving the hippocampal formation and diencephalon.

Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium-Pilocarpine-Induced Status Epilepticus.

The administration of lithium–pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS. Thus, we performed high-performance liquid chromatography (HPLC) to quantify levels of amino acids and monoamines, and c-Fos immunohistochemical labeling to map cerebral activation during seizures. Comparing rats treated one hour after SE onset with saline (CT), CRS, or diazepam (DZP), HPLC showed that 4 h after SE onset, dopamine (DA), norepinephrine (NE), and GABA levels were normal, whereas serotonin levels were increased. Using c-Fos labeling, we demonstrated increased activity in thalamic mediodorsal (MD) and laterodorsal (LD) nuclei in rats treated with CRS. In summary, at early times, CRS seems to modulate excitability by acting on some monoamine levels and increasing activity of MD and LD thalamic nuclei, suggesting a possible involvement of these nuclei in insult- and/or epileptogenesis-modifying effects of CRS.

Stereotaxic 18F-FDG PET and MRI templates with three-dimensional digital atlas for statistical parametric mapping analysis of tree shrew brain

BackgroundTree shrews are proposed as an alternative animal model to nonhuman primates due to their close affinity to primates. Neuroimaging techniques are widely used to study brain functions and structures of humans and animals. However, tree shrews are rarely applied in neuroimaging field partly due to the lack of available species specific analysis methods. New methodIn this study, 10 PET/CT and 10 MRI images of tree shrew brain were used to construct PET and MRI templates; based on histological atlas we reconstructed a three-dimensional digital atlas with 628 structures delineated; then the digital atlas and templates were aligned into a stereotaxic space. Finally, we integrated the digital atlas and templates into a toolbox for tree shrew brain spatial normalization, statistical analysis and results localization. ResultsWe validated the feasibility of the toolbox by simulated data with lesions in laterodorsal thalamic nucleus (LD). The lesion volumes of simulated PET and MRI images were (12.97±3.91)mm3 and (7.04±0.84)mm3. Statistical results at p<0.005 showed the lesion volumes of PET and MRI were 13.18mm3 and 8.06mm3 in LD. Comparison with existing method(s)To our knowledge, we report the first PET template and digital atlas of tree shrew brain. Compared to the existing MRI templates, our MRI template was aligned into stereotaxic space. And the toolbox is the first software dedicated for tree shrew brain analysis. ConclusionsThe templates and digital atlas of tree shrew brain, as well as the toolbox, facilitate the use of tree shrews in neuroimaging field.

Asymmetric cross-hemispheric connections link the rat anterior thalamic nuclei with the cortex and hippocampal formation

Dense reciprocal connections link the rat anterior thalamic nuclei with the prelimbic, anterior cingulate and retrosplenial cortices, as well as with the subiculum and postsubiculum. The present study compared the ipsilateral thalamic-cortical connections with the corresponding crossed, contralateral connections between these same sets of regions. All efferents from the anteromedial thalamic nucleus to the cortex, as well as those to the subiculum, remained ipsilateral. In contrast, all of these target sites provided reciprocal, bilateral projections to the anteromedial nucleus. While the anteroventral thalamic nucleus often shared this same asymmetric pattern of cortical connections, it received relatively fewer crossed inputs than the anteromedial nucleus. This difference was most marked for the anterior cingulate projections, as those to the anteroventral nucleus remained almost entirely ipsilateral. Unlike the anteromedial nucleus, the anteroventral nucleus also appeared to provide a restricted, crossed projection to the contralateral retrosplenial cortex. Meanwhile, the closely related laterodorsal thalamic nucleus had almost exclusively ipsilateral efferent and afferent cortical connections. Likewise, within the hippocampus, the postsubiculum seemingly had only ipsilateral efferent and afferent connections with the anterior thalamic and laterodorsal nuclei. While the bilateral cortical projections to the anterior thalamic nuclei originated predominantly from layer VI, the accompanying sparse projections from layer V largely gave rise to ipsilateral thalamic inputs. In testing a potentially unifying principle of anterior thalamic – cortical interactions, a slightly more individual pattern emerged that reinforces other evidence of functional differences within the anterior thalamic and also helps to explain the consequences of unilateral interventions involving these nuclei.

Cholinergic profiles in the Goettingen miniature pig (Sus scrofa domesticus) brain.

Central cholinergic structures within the brain of the even-toed hoofed Goettingen miniature domestic pig (Sus scrofa domesticus) were evaluated by immunohistochemical visualization of choline acetyltransferase (ChAT) and the low-affinity neurotrophin receptor, p75NTR . ChAT-immunoreactive (-ir) perikarya were seen in the olfactory tubercle, striatum, medial septal nucleus, vertical and horizontal limbs of the diagonal band of Broca, and the nucleus basalis of Meynert, medial habenular nucleus, zona incerta, neurosecretory arcuate nucleus, cranial motor nuclei III and IV, Edinger-Westphal nucleus, parabigeminal nucleus, pedunculopontine nucleus, and laterodorsal tegmental nucleus. Cholinergic ChAT-ir neurons were also found within transitional cortical areas (insular, cingulate, and piriform cortices) and hippocampus proper. ChAT-ir fibers were seen throughout the dentate gyrus and hippocampus, in the mediodorsal, laterodorsal, anteroventral, and parateanial thalamic nuclei, the fasciculus retroflexus of Meynert, basolateral and basomedial amygdaloid nuclei, anterior pretectal and interpeduncular nuclei, as well as select laminae of the superior colliculus. Double immunofluorescence demonstrated that virtually all ChAT-ir basal forebrain neurons were also p75NTR -positive. The present findings indicate that the central cholinergic system in the miniature pig is similar to other mammalian species. Therefore, the miniature pig may be an appropriate animal model for preclinical studies of neurodegenerative diseases where the cholinergic system is compromised. J. Comp. Neurol. 525:553-573, 2017. © 2016 Wiley Periodicals, Inc.

GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: A post-mortem study

BackgroundGlutamic acid decarboxylase (GAD) is a key enzyme in GABA synthesis and alterations in GABAergic neurotransmission related to glial abnormalities are thought to play a crucial role in the pathophysiology of schizophrenia. This study aimed to identify potential differences regarding the neuropil expression of GAD between paranoid and residual schizophrenia. MethodsGAD65/67 immunostained histological sections were evaluated by quantitative densitometric analysis of GAD-immunoreactive (ir) neuropil. Regions of interest were the hippocampal formation (CA1 field and dentate gyrus [DG]), superior temporal gyrus (STG), and laterodorsal thalamic nucleus (LD). Data from 16 post-mortem schizophrenia patient samples (10 paranoid and 6 residual schizophrenia cases) were compared with those from 16 matched controls. ResultsOverall, schizophrenia patients showed a lower GAD-ir neuropil density (P=0.014), particularly in the right CA1 (P=0.033). However, the diagnostic subgroups differed significantly (P<0.001), mainly because of lower right CA1 GAD-ir neuropil density in paranoid versus residual patients (P=0.036) and controls (P<0.003). Significant GAD-ir neuropil reduction was also detected in the right STG layer V of paranoid versus residual schizophrenia cases (P=0.042). GAD-ir neuropil density correlated positively with antipsychotic dosage, particularly in CA1 (right: r=0.850, P=0.004; left: r=0.800, P=0.010). ConclusionOur finding of decreased relative density of GAD-ir neuropil suggests hypofunction of the GABAergic system, particularly in hippocampal CA1 field and STG layer V of patients with paranoid schizophrenia. The finding that antipsychotic medication seems to counterbalance GABAergic hypofunction in schizophrenia patients suggests the possibility of exploring new treatment avenues which target this system.

Cognitive impairments and neuronal injury in different brain regions of a genetic rat model of absence epilepsy

Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6months of age. The learning and memory performances were assessed using passive avoidance paradigm and neuropathological alterations were investigated by the evaluation of the number of dark neurons and apoptotic cells as well as the expression of caspase-3 in the neocortex, the hippocampus, and different regions of the thalamus. Results revealed a decline in learning and spatial memory of 6-month-old WAG/Rij rats compared to age-matched Wistar rats as well as 2-month-old WAG/Rij and Wistar rats. The mean number of dark neurons was significantly higher in the hippocampal CA1 and CA3 areas as well as in the laterodorsal, centromedial, and reticular thalamic nuclei and the somatosensory cortex of 6-month-old WAG/Rij rats. In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy.

Fornical and nonfornical projections from the rat hippocampal formation to the anterior thalamic nuclei.

ABSTRACTThe hippocampal formation and anterior thalamic nuclei form part of an interconnected network thought to support memory. A central pathway in this mnemonic network comprises the direct projections from the hippocampal formation to the anterior thalamic nuclei, projections that, in the primate brain, originate in the subicular cortices to reach the anterior thalamic nuclei by way of the fornix. In the rat brain, additional pathways involving the internal capsule have been described, linking the dorsal subiculum to the anteromedial thalamic nucleus, as well as the postsubiculum to the anterodorsal thalamic nucleus. Confirming such pathways is essential in order to appreciate how information is transferred from the hippocampal formation to the anterior thalamus and how it may be disrupted by fornix pathology. Accordingly, in the present study, pathway tracers were injected into the anterior thalamic nuclei and the dorsal subiculum of rats with fornix lesions. Contrary to previous descriptions, projections from the subiculum to the anteromedial thalamic nucleus overwhelmingly relied on the fornix. Dorsal subiculum projections to the majority of the anteroventral nucleus also predominantly relied on the fornix, although postsubicular inputs to the lateral dorsal part of the anteroventral nucleus, as well as to the anterodorsal and laterodorsal thalamic nuclei, largely involved a nonfornical pathway, via the internal capsule. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Role of Laterodorsal Thalamic Nucleus during Absence Seizure Attacks

Introduction: A typical absence epilepsy is a type of nonconvulsive and generalized epilepsy. The main feature of these attacks is a sudden brief impairment of consciousness. The disturbances in thalamocortical loop play an important role in pathogenesis of absence seizures. However, it is not clear that which part of this network triggers the seizure. This study was aimed to investigate the role of latrodorsal (LD) thalamic neurons during spike and wave discharges (SWDs) in WAG/Rij rats, as the most valid animal model of absence epilepsy. Materials and Methods: Single unit activities in the LD thalamic nucleus and electrocorticogram of somatosensory cortex were simultaneously recorded in six-month-old WAG/Rij rats. Results: During SWDs, unit activity in the LD thalamic nucleus showed burstlike discharges, which were started before the peak component of SWDs. In SWD-free periods, burst like activity in the LD was reduced. Conclusion: Our findings suggest that the burst firing of LD may stimulate the neocortex to exhibit SWDs. It can be concluded that inhibition of

Calcium-binding proteins in the laterodorsal thalamic nucleus during development of the guinea pig

The laterodorsal thalamic nucleus (LD) is often treated as a part of the anterior thalamic nuclei (ATN) because of its location and similar connectivity. Our previous studies have shown that distribution of three calcium-binding proteins, i.e. calbindin D28k (CB), calretinin (CR) and parvalbumin (PV), changes within the ATN during development of the guinea pig. The aim of this study is to examine the immunoreactivity pattern of these proteins in the LD in the guinea pig ontogeny. Brains from animals ranging from 40th embryonic day to 80th postnatal day were used in the study. Two methods were applied: a single-labelling immunoenzymatic method and double-labelling immunofluorescence. No changes of the distribution pattern of the substances were observed throughout the examined developmental stages. CB and CR were the most abundantly expressed proteins in perikarya of the LD. Numerous CB- and CR-immunoreactive cell bodies were found throughout the whole extent of the nucleus. In most of these cell bodies both proteins colocalized vastly. The highest immunoreactivity of the perikarya containing CB and CR was observed in the mediodorsal part of the LD and in its rostral portion. In regard to PV, single cell bodies were observed mostly in the dorsal part of the nucleus. PV did not colocalize with the other proteins. In summary, all the studied calcium-binding proteins were already present in the LD at prenatal developmental stages and the pattern of distribution remained virtually constant until adulthood. Thus, the LD differs considerably from the ATN in an aspect of neurochemical cell differentiation.