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Brain Research Mar 2019Inhibitory circuits in thalamus and cortex shape the major activity patterns observed by electroencephalogram (EEG) in the adult brain. Their delayed maturation and... (Review)
Review
Inhibitory circuits in thalamus and cortex shape the major activity patterns observed by electroencephalogram (EEG) in the adult brain. Their delayed maturation and circuit integration, relative to excitatory neurons, suggest inhibitory neuronal development could be responsible for the onset of mature thalamocortical activity. Indeed, the immature brain lacks many inhibition-dependent activity patterns, such as slow-waves, delta oscillations and sleep-spindles, and instead expresses other unique oscillatory activities in multiple species including humans. Thalamus contributes significantly to the generation of these early oscillations. Compared to the abundance of studies on the development of inhibition in cortex, however, the maturation of thalamic inhibition is poorly understood. Here we review developmental changes in the neuronal and circuit properties of the thalamic relay and its interconnected inhibitory thalamic reticular nucleus (TRN) both in vitro and in vivo, and discuss their potential contribution to early network activity and its maturation. While much is unknown, we argue that weak inhibitory function in the developing thalamus allows for amplification of thalamocortical activity that supports the generation of early oscillations. The available evidence suggests that the developmental acquisition of critical thalamic oscillations such as slow-waves and sleep-spindles is driven by maturation of the TRN. Further studies to elucidate thalamic GABAergic circuit formation in relation to thalamocortical network function would help us better understand normal as well as pathological brain development.
Topics: Action Potentials; Animals; Brain; Cerebral Cortex; Electroencephalography; Humans; Midline Thalamic Nuclei; Nerve Net; Neurons; Sleep; Thalamic Nuclei; Thalamus
PubMed: 30366019
DOI: 10.1016/j.brainres.2018.10.024 -
Neuron Aug 2021Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms...
Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.
Topics: Animals; Anterior Thalamic Nuclei; Cerebral Cortex; Cognition; Cognitive Dysfunction; Mice; Neural Pathways; Thalamic Nuclei
PubMed: 34197733
DOI: 10.1016/j.neuron.2021.06.005 -
Neuroscience and Biobehavioral Reviews Jul 2015The thalamus was subdivided into three major groups: sensorimotor nuclei (or principal/relay nuclei), limbic nuclei and nuclei bridging these two domains. Limbic nuclei... (Review)
Review
The thalamus was subdivided into three major groups: sensorimotor nuclei (or principal/relay nuclei), limbic nuclei and nuclei bridging these two domains. Limbic nuclei of thalamus (or 'limbic thalamus') consist of the anterior nuclei, midline nuclei, medial division of the mediodorsal nucleus (MDm) and central medial nucleus (CM) of the intralaminar complex. The midline nuclei include the paraventricular (PV) and paratenial (PT) nuclei, dorsally, and the reuniens (RE) and rhomboid (RH) nuclei, ventrally. The 'limbic' thalamic nuclei predominantly connect with limbic-related structures and serve a direct role in limbic-associated functions. Regarding the midline nuclei, RE/RH mainly target limbic cortical structures, particularly the hippocampus and the medial prefrontal cortex. Accordingly, RE/RH participate in functions involving interactions of the HF and mPFC. By contrast, PV/PT mainly project to limbic subcortical structures, particularly the amygdala and nucleus accumbens, and hence are critically involved in affective behaviors such as stress/anxiety, feeding behavior, and drug seeking activities. The anatomical/functional characteristics of MDm and CM are very similar to those of the midline nuclei and hence the collection of nuclei extending dorsoventrally along the midline/paramidline of the thalamus constitute the core of the 'limbic thalamus'.
Topics: Animals; Humans; Limbic System; Midline Thalamic Nuclei; Neural Pathways
PubMed: 25616182
DOI: 10.1016/j.neubiorev.2015.01.014 -
Brain and Language Jul 2013Thalamic nuclei associated with language including the ventral lateral, ventral anterior, intralaminar and mediodorsal form a hub that uniquely receives the output of... (Review)
Review
Thalamic nuclei associated with language including the ventral lateral, ventral anterior, intralaminar and mediodorsal form a hub that uniquely receives the output of the basal ganglia and cerebellum, and is connected with frontal (premotor and prefrontal) cortices through two parallel circuits: a thalamic pathway targets the middle frontal cortical layers focally, and the other innervates widely cortical layer 1, poised to recruit other cortices and thalamic nuclei for complex cognitive operations. Return frontal pathways to the thalamus originate from cortical layers 6 and 5. Information through this integrated thalamo-cortical system is gated by the inhibitory thalamic reticular nucleus and modulated by dopamine, representing a specialization in primates. The intricate dialogue of distinct thalamic nuclei with the basal ganglia, cerebellum, and specific dorsolateral prefrontal and premotor cortices associated with language, suggests synergistic roles in the complex but seemingly effortless sequential transformation of cognitive operations for speech production in humans.
Topics: Frontal Lobe; Humans; Language; Neural Pathways; Speech; Thalamic Nuclei
PubMed: 23211411
DOI: 10.1016/j.bandl.2012.10.001 -
Human Brain Mapping Dec 2021It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is...
It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear-specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non-refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting-state functional magnetic resonance imaging (MRI) in patients with refractory and non-refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed-to-voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non-refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non-refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting-state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.
Topics: Adult; Aged; Cerebral Cortex; Connectome; Drug Resistant Epilepsy; Epilepsy, Generalized; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Thalamic Nuclei; Young Adult
PubMed: 34432348
DOI: 10.1002/hbm.25644 -
The American Journal of Psychiatry Dec 2020Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided...
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Adult; Atrophy; Case-Control Studies; Cognition; Cross-Sectional Studies; Female; Humans; Male; Neuropsychological Tests; Psychotic Disorders; Thalamic Nuclei; Young Adult
PubMed: 32911995
DOI: 10.1176/appi.ajp.2020.19101099 -
European Journal of Histochemistry : EJH Mar 2022The thalamic reticular nucleus (TRN) projects inhibitory signals to the thalamus, thereby controlling thalamocortical connections. Few studies have examined the...
The thalamic reticular nucleus (TRN) projects inhibitory signals to the thalamus, thereby controlling thalamocortical connections. Few studies have examined the development of TRN projections to the anterior thalamic nuclei with regard to axon course and the axon terminal distributions. In the present study, we used parvalbumin (PV) immunostaining to investigate inhibitory projections from the TRN to the thalamus in postnatal (P) 2- to 5-week-old rats (P14-35). The distribution of PV-positive (+) nerve fibers and nerve terminals markedly differed among the anterior thalamic nuclei at P14. Small, beaded nerve terminals were more distributed throughout the anterodorsal nucleus (AD) than in the anteroventral nucleus (AV) and anteromedial nucleus (AM). PV+ fibers traveling from the TRN to the AD were observed in the AV and AM. Nodular nerve terminals, spindle or en passant terminals, were identified on the axons passing through the AV and AM. At P21, axon bundles traveling without nodular terminals were observed, and nerve terminals were distributed throughout the AV and AM similar to the AD. At P28 and P35, the nerve terminals were evenly distributed throughout each nucleus. In addition, DiI tracer injections into the retrosplenial cortex revealed retrogradely-labeled projection neurons in the 3 nuclei at P14. At P14, the AD received abundant projections from the TRN and then projected to the retrosplenial cortex. The AV and AM seem to receive projections with distinct nodular nerve terminals from the TRN and project to the retrosplenial cortex. The projections from TRN to the AV and AM with nodular nerve terminals at P14 are probably developmental-period specific. In comparison, the TRN projections to the AD at P14 might be related to the development of spatial navigation as part of the head orientation system.
Topics: Animals; Anterior Thalamic Nuclei; Rats; Thalamic Nuclei
PubMed: 35330554
DOI: 10.4081/ejh.2022.3370 -
Neurobiology of Disease Mar 2023Spike-and-wave discharges (SWDs), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence...
Spike-and-wave discharges (SWDs), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence seizures (ASs). SWDs begin in a cortical initiation network in both humans and animal models, including the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), where it is located in the primary somatosensory cortex (S1). The behavioral manifestation of an AS occurs when SWDs spread from the cortical initiation site to the whole brain, however, the mechanisms behind this rapid propagation remain unclear. Here we investigated these processes beyond the principal CTC network, in higher-order (HO) thalamic nuclei (lateral posterior (LP) and posterior (PO) nuclei) since their diffuse connectivity and known facilitation of intracortical communications make these nuclei key candidates to support SWD generation and maintenance. In freely moving GAERS, multi-site LFP in LP, PO and multiple cortical regions revealed a novel feature of SWDs: during SWDs there are short periods (named SWD-breaks) when cortical regions far from S1, such the primary visual cortex (V1), become transiently unsynchronized from the ongoing EEG rhythm. Inactivation of HO nuclei with local muscimol injections or optogenetic perturbation of HO nuclei activity increased the occurrence of SWD-breaks and the former intervention also increased the SWD propagation-time from S1. The neural underpinnings of these findings were explored further by silicon probe recordings from single units of PO which uncovered two previously unknown groups of excitatory neurons based on their burst firing dynamics at SWD onset. Moreover, a switch from tonic to burst firing at SWD onset was shown to be an important feature since it was much less prominent for non-generalized events, i.e. SWDs that remained local to S1. Additionally, one group of neurons showed a reverse of this switch during SWD-breaks, demonstrating the importance of this firing pattern throughout the SWD. In summary, these results support the view that multiple HO thalamic nuclei are utilized at SWD onset and contribute to cortical synchrony throughout the paroxysmal discharge.
Topics: Humans; Rats; Animals; Epilepsy, Absence; Electroencephalography; Thalamic Nuclei; Seizures; Neurons; Thalamus; Disease Models, Animal
PubMed: 36731682
DOI: 10.1016/j.nbd.2023.106025 -
NeuroImage Sep 2017The thalamus consists of multiple nuclei that have been previously defined by their chemoarchitectual and cytoarchitectual properties ex vivo. These form discrete,...
The thalamus consists of multiple nuclei that have been previously defined by their chemoarchitectual and cytoarchitectual properties ex vivo. These form discrete, functionally specialized, territories with topographically arranged graduated patterns of connectivity. However, previous in vivo thalamic parcellation with MRI has been hindered by substantial inter-individual variability or discrepancies between MRI derived segmentations and histological sections. Here, we use the Euclidean distance to characterize probabilistic tractography distributions derived from diffusion MRI. We generate 12 feature maps by performing voxel-wise parameterization of the distance histograms (6 feature maps) and the distribution of three-dimensional distance transition gradients generated by applying a Sobel kernel to the distance metrics. We use these 12 feature maps to delineate individual thalamic nuclei, then extract the tractography profiles for each and calculate the voxel-wise tractography gradients. Within each thalamic nucleus, the tractography gradients were topographically arranged as distinct non-overlapping cortical networks with transitory overlapping mid-zones. This work significantly advances quantitative segmentation of the thalamus in vivo using 3T MRI. At an individual subject level, the thalamic segmentations consistently achieve a close relationship with a priori histological atlas information, and resolve in vivo topographic gradients within each thalamic nucleus for the first time. Additionally, these techniques allow individual thalamic nuclei to be closely aligned across large populations and generate measures of inter-individual variability that can be used to study both basic function and pathological processes in vivo.
Topics: Adult; Brain Mapping; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Neural Pathways; Thalamic Nuclei
PubMed: 27639355
DOI: 10.1016/j.neuroimage.2016.08.028 -
Trends in Neurosciences Oct 2016The thalamus is the major source of cortical inputs shaping sensation, action, and cognition. Thalamic circuits are targeted by two major inhibitory systems: the... (Review)
Review
The thalamus is the major source of cortical inputs shaping sensation, action, and cognition. Thalamic circuits are targeted by two major inhibitory systems: the thalamic reticular nucleus (TRN) and extrathalamic inhibitory (ETI) inputs. A unifying framework of how these systems operate is currently lacking. Here, we propose that TRN circuits are specialized to exert thalamic control at different spatiotemporal scales. Local inhibition of thalamic spike rates prevails during attentional selection, whereas global inhibition more likely prevails during sleep. In contrast, the ETI (arising from basal ganglia, zona incerta (ZI), anterior pretectum, and pontine reticular formation) provides temporally precise and focal inhibition, impacting spike timing. Together, these inhibitory systems allow graded control of thalamic output, enabling thalamocortical operations to dynamically match ongoing behavioral demands.
Topics: Action Potentials; Animals; Basal Ganglia; Humans; Inhibition, Psychological; Nerve Net; Thalamic Nuclei; Thalamus
PubMed: 27589879
DOI: 10.1016/j.tins.2016.08.001