The corticothalamic system is organized to play a key role in synchronizing the activities of thalamic and cortical neurons. Its synapses dominate the inputs to relay cells and to the GABAergic cells ...of the reticular nucleus; its organization in focused and diffuse projections promotes both coherent activity of relay neurons and the spread of activity across the cortex and thalamus. The capacity of relay neurons to operate in voltage‐dependent tonic or burst mode permits corticothalamic inputs to directly excite the relay cells or indirectly inhibit them via the reticular nucleus. This enables the corticothalamic projection to synchronize high‐ or low‐frequency oscillatory activity, respectively, in the thalamo–corticothalamic network. Differences in the subunit composition of AMPA receptors at synapses formed by branches of the same corticothalamic axon in the reticular nucleus and dorsal thalamus are an important element in the capacity of the cortex to synchronize low‐frequency oscillations in the network. Intrinsic voltage‐gated calcium channels of different kinds expressed in the relay neurons form a substrate for corticothalamic interactions with the relay cells that promote high‐ or low‐frequency oscillations. Focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, in conjunction with the core and matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high‐frequency oscillations that underlie discrete conscious events.
The sudden collapse of thawing soils in the Arctic might double the warming from greenhouse gases released from tundra, warn Merritt R. Turetsky and colleagues.
High-frequency synchronous activity of neurons in the cerebral cortex and thalamus is a concomitant of discrete conscious events. In the primate thalamus, a newly identified population of neurons ...provides a basis for this synchronization. A matrix of calbindin-immunoreactive neurons extends throughout the thalamus and projects to superficial layers of cortex over wide areas, unconstrained by boundaries between areas. In some nuclei, a core of parvalbumin-immunoreactive neurons is superimposed upon the matrix. Core neurons project in a topographically ordered fashion to middle layers of the cortex in an area-specific manner. Matrix neurons, recruited by corticothalamic connections, can disperse activity across cortical areas and thalamic nuclei. Their superficial terminations can synchronize specific and nonspecific elements of the thalamocortical network in coherent activity that underlies cognitive events.
A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients ...who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1) , and BHLHE41(DEC2) . The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.
Thalamic circuitry and thalamocortical synchrony Jones, Edward G.; Jones, Edward G.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
12/2002, Letnik:
357, Številka:
1428
Journal Article
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The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the γ-amino ...butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage-dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high- or low-frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.
Mitochondria provide most of the energy for brain cells by the process of oxidative phosphorylation. Mitochondrial abnormalities and deficiencies in oxidative phosphorylation have been reported in ...individuals with schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) in transcriptomic, proteomic, and metabolomic studies. Several mutations in mitochondrial DNA (mtDNA) sequence have been reported in SZ and BD patients.
Dorsolateral prefrontal cortex (DLPFC) from a cohort of 77 SZ, BD, and MDD subjects and age-matched controls (C) was studied for mtDNA sequence variations and heteroplasmy levels using Affymetrix mtDNA resequencing arrays. Heteroplasmy levels by microarray were compared to levels obtained with SNaPshot and allele specific real-time PCR. This study examined the association between brain pH and mtDNA alleles. The microarray resequencing of mtDNA was 100% concordant with conventional sequencing results for 103 mtDNA variants. The rate of synonymous base pair substitutions in the coding regions of the mtDNA genome was 22% higher (p = 0.0017) in DLPFC of individuals with SZ compared to controls. The association of brain pH and super haplogroup (U, K, UK) was significant (p = 0.004) and independent of postmortem interval time.
Focusing on haplogroup and individual susceptibility factors in psychiatric disorders by considering mtDNA variants may lead to innovative treatments to improve mitochondrial health and brain function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The neocortex of primates, including humans, is thought to contain significantly higher numbers and more diverse forms of γ-aminobutyric acidergic (GABAergic) interneurons than that of rodents. The ...mouse cortex displays a number of other features that distinguish it from the cortex of primates and suggest a somewhat less complex pattern of organization. Nevertheless, dramatic findings on the origins and migratory patterns of newly specified GABAergic cortical interneurons in the embryonic mouse have led to a prevailing view that GABAergic cortical interneurons of all species are born in the ganglionic eminence and undergo the same long tangential migration toward the cortex that is seen in the mouse. Recent observations in fetal human and monkey brains, although clearly identifying GABAergic neurons that reach the neocortex via the tangential route, also demonstrate that substantial numbers of GABA neurons are generated in the lateral ventricular neuroepithelium and migrate into the cortex via the same radial route followed by glutamatergic neurons. In the course of evolution of the higher primate cortex, it is likely that new forms of cortical interneuron with origins in the ventricular neuroepithelium have been added to an older population derived from the ganglionic eminence.
After manipulations of the periphery that reduce or enhance input to the somatosensory cortex, affected parts of the body representation will contract or expand, often over many millimeters. Various ...mechanisms, including divergence of preexisting connections, expression of latent synapses, and sprouting of new synapses, have been proposed to explain such phenomena, which probably underlie altered sensory experiences associated with limb amputation and peripheral nerve injury in humans. Putative cortical mechanisms have received the greatest emphasis but there is increasing evidence for substantial reorganization in subcortical structures, including the brainstem and thalamus, that may be of sufficient extent to account for or play a large part in representational plasticity in somatosensory cortex. Recent studies show that divergence of ascending connections is considerable and sufficient to ensure that small alterations in map topography at brainstem and thalamic levels will be amplified in the projection to the cortex. In the long term, slow, deafferentation-dependent transneuronal atrophy at brainstem, thalamic, and even cortical levels are operational in promoting reorganizational changes, and the extent to which surviving connections can maintain a map is a key to understanding differences between central and peripheral deafferentation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Psychiatric disorders are multigenic diseases with complex etiology that contribute significantly to human morbidity and mortality. Although clinically distinct, several disorders share many ...symptoms, suggesting common underlying molecular changes exist that may implicate important regulators of pathogenesis and provide new therapeutic targets.
We performed RNA sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal cortex, and nucleus accumbens from three groups of 24 patients each diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, and from 24 control subjects. We identified differentially expressed genes and validated the results in an independent cohort. Anterior cingulate cortex samples were also subjected to metabolomic analysis. ChIP-seq data were used to characterize binding of the transcription factor EGR1.
We compared molecular signatures across the three brain regions and disorders in the transcriptomes of post-mortem human brain samples. The most significant disease-related differences were in the anterior cingulate cortex of schizophrenia samples compared to controls. Transcriptional changes were assessed in an independent cohort, revealing the transcription factor EGR1 as significantly down-regulated in both cohorts and as a potential regulator of broader transcription changes observed in schizophrenia patients. Additionally, broad down-regulation of genes specific to neurons and concordant up-regulation of genes specific to astrocytes was observed in schizophrenia and bipolar disorder patients relative to controls. Metabolomic profiling identified disruption of GABA levels in schizophrenia patients.
We provide a comprehensive post-mortem transcriptome profile of three psychiatric disorders across three brain regions. We highlight a high-confidence set of independently validated genes differentially expressed between schizophrenia and control patients in the anterior cingulate cortex and integrate transcriptional changes with untargeted metabolite profiling.
Switching of the NMDA receptor 2A (NR2A) and NR2B subunits at NMDA receptors is thought to underlie the functional changes that occur in NMDA receptor properties during the developmental epoch when ...neural plasticity is most pronounced. The cellular expression of NR2A and NR2B and the NR2 synaptic binding protein postsynaptic density-95 (PSD-95) was examined in the mouse somatosensory cortex and thalamus from postnatal day 2 (P2) to P15 using reverse transcription-PCR, in situ hybridization histochemistry, and immunocytochemistry. The localization of NR2A and NR2B subunits and PSD-95 was then studied at synapses in layer IV of somatosensory cortex and in the ventral posterior nucleus of the thalamus using high-resolution immunoelectron microscopy. At both cortical and thalamic synapses, a quantitative switch in the dominant synaptic subunit from NR2B to NR2A was accompanied by a similar change in the cellular expression of NR2A but not of NR2B. Synaptic PSD-95 developed independently, although both NR2A and NR2B colocalized with PSD-95. Displacement of NR2B subunits from synapses was not accompanied by an increase in an extrasynaptic pool of this subunit. Thus, the switch in synaptic NR2 subunit predominance does not occur by changes in expression or displacement from synapses and may reflect the formation of new synapses from which NR2B is lacking.
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