Thalamus & related systems最新文献

The goal of the present study was to determine if the medial agranular cortex (AGm) that is thought to contain the supplementary motor area in the rat receives the pallidothalamocortical pathway. A double labeling paradigm was employed whereby injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the entopeduncular nucleus (EN) were combined with injections of the retrograde tracer cholera toxin subunit B into either the rostral or caudal part AGm in the rat. We found that the pallidothalamic projections occupied a crescent shaped arc within the thalamic ventral anterior-ventral lateral nuclear complex (VAL) and ventral medial nucleus (VM). Additional efferents projected to LD/LP, MD, Pf and CL. Dense projections were also found to LHb. In addition, we found that a wide band of cells extending from rostral thalamus including VAL and VM through caudal thalamus including MD, Po, LD/LP, Pf and CL projected to either the rostral or caudal parts of the AGm. The greatest coincidence of the pallidothalamic efferents and AGm thalamocortical cells was found in VAL and VM where numerous PHA-L varicosities were found in close apposition to CTB labeled cells. Synaptic contacts between VAL thalamocortical neurons and pallidal terminals were verified in the electron microscope. These results demonstrate for the first time the pallidothalamocortical pathway by way of VAL to the AGm in the rat.

Having shown a decrease in muscarinic M1 receptors in Brodmann’s area (BA) 9 from subjects with schizophrenia we have extended our studies to determine if this receptor is decreased in the thalamus from the same cohort of subjects. Levels of $\text{[}{}^3\text{H}\text{]}$pirenzepine binding to and mRNA encoding for M1 and M4 receptors were measured throughout the thalamus. Levels of M1 and M4 receptor proteins were measured in the mediodorsal nucleus. Two-way ANOVA revealed a variance in $\text{[}{}^3\text{H}\text{]}$pirenzepine binding (F=4.69, d.f. = 1.190, P=0.03), but there was no significant change in radioligand binding in any thalamic region in schizophrenia. Neither levels of mRNA encoding the thalamic M1 or M4 receptor nor levels of M1 or M4 receptor protein in the mediodorsal nucleus differed between the schizophrenic and control subjects. We therefore conclude that the M1 and M4 receptor are not altered in the thalamus from subjects with schizophrenia. These data add weight to the hypothesis that changes in M1 receptors in selective regions of the CNS are associated with the pathology of schizophrenia.

We found a shift in the responsiveness of pedunculopontine neurons from N-methyl-d-aspartic acid (NMDA) to kainic acid (KA) regulation around 15 days of age. While rapid eye movement (REM) sleep in humans decreases from 50 to 15% of sleep time between birth and the end of puberty, a similar decrease in the rat occurs from 10 to 30 days postnatally. Intracellularly recorded type II cholinergic PPN neurons, known to modulate waking and REM sleep, showed a gradual decrease in responsiveness to NMDA, and an increase in responsiveness to KA, during this period. Non-cholinergic PPN neurons did not show a developmental-dependent change in responsiveness. These results do not help explain if KA and NMDA control the developmental decrease in REM sleep, however, the data indicate that the shift at ∼15 days suggests that REM sleep becomes selectively modulated by KA receptors in the adult. Therefore, given development of appropriate compounds, KA receptor antagonism may become an effective treatment for disorders that manifest increased REM sleep drive and produce frequent nocturnal arousals and awakenings, e.g. schizophrenia, anxiety, insomnia, etc.

The ventral anterior (VA) nucleus of the thalamus is connected with prefrontal and premotor cortices and with the basal ganglia. Although classically associated with motor functions, recent evidence implicates the basal ganglia in cognition and emotion as well. Here, we used two complementary approaches to investigate whether the VA is a key link for pathways underlying cognitive and emotional processes through prefrontal cortices and the basal ganglia. After application of bidirectional tracers in functionally distinct lateral, medial, and orbitofrontal cortices, we found that projection neurons were embedded in much larger patches of axonal terminations found in the magnocellular part of VA (VAmc), and in the principal part of VA. Connections from medial prefrontal cortices occupied the dorsomedial and ventromedial VA, and orbitofrontal connections were found in ventrolateral VAmc. Moreover, about half of all projection neurons in orbitofrontal areas directed to the VA or VAmc were positive for calbindin but not parvalbumin, even though comparable populations of neurons were positive for each marker in the VA. We then applied tracers in VA and investigated simultaneously projections from all prefrontal areas, the internal segment of the globus pallidus (GPi), the substantia nigra reticulata (SNr), and the thalamic reticular nucleus. Projection neurons were most densely distributed in anterior cingulate areas 24 and 32, and dorsolateral areas 9 and 8, innervating the same VA sites that received projections from a large part of GPi and dorsal SNr. Nearly as many projection neurons originated from cortical layer V as from layer VI. There is evidence that cortical layer VI neurons innervate thalamic neurons that project focally to the middle cortical layers, whereas layer V neurons synapse with thalamic neurons projecting widely to cortical layer I. Projections from layer V to the VA may facilitate cortical recruitment for executive functions within a cognitive context through lateral prefrontal areas, and autonomic responses within an emotional context through anterior cingulate areas.

Postmortem and in vivo imaging studies have revealed structural and functional pathology in the thalamus in schizophrenia. We have reported a series neurochemical changes in the thalamus in schizophrenia, including decreased expression of NMDA receptor subunit transcripts and increased levels of NMDA receptor-associated intracellular proteins like postsynaptic density protein 95 (PSD95) and neurofilament-light (NF-L) chain that link the NMDA receptor to downstream signal transduction pathways. NF-L, along with the neurofilament subunit proteins NF-medium (NF-M) chain and NF-heavy (NF-H) chain, assemble to form neurofilaments, one of the most abundant cytoskeletal elements. While the neurofilament subunits play a crucial role in sustaining the neuronal cytoskeleton, two subunits, NF-L and NF-M, also participate in neurotransmission, interacting with the NMDA and the dopamine D1 receptors, respectively. In the present study, using in situ hybridization, we determined whether all of the neurofilament subunits (NF-L, NF-M, and NF-H) are abnormally expressed in the thalamus in schizophrenia, or whether the abnormality is specific to NF-L. We found that NF-L and NF-M transcripts are both increased in schizophrenia, but the expression of NF-H is unchanged. Both NF-L and NF-M play an important role in maintaining the neuronal cytoskeleton, so abnormal transcript expression may be associated with structural thalamic pathology. Alternatively, since these proteins are also known to interact with the NMDA and D1 dopamine receptors, abnormal transcript levels may be associated with abnormalities of neurotransmission in the thalamus in schizophrenia.