Thalamus & related systems最新文献

This paper provides an overview of the major organizational features of the basal ganglia and related thalamic centers, as delineated by the application of single-axon or single-cell labeling procedures in primates. These studies have revealed that the striatum, the external pallidum and the subthalamic nucleus harbor several types of projection neurons endowed with a highly collateralized axon that allows these neurons to interact with most components of the basal ganglia. In contrast, the internal pallidum, which is a major output structure of the basal ganglia, contains only two types of projection neurons. First, there is a minority of “limbic” pallidal neurons with a poorly branched axon that arborized profusely within the lateral habenula, which stands out as the most densely innervated pallidal target. Second, there is a majority of pallidal “motor” neurons with a long (total axonal length up to 27 cm) and highly branched axon that provides collaterals to the ventral tiers thalamic nuclei, the brainstem pedunculopontine nucleus and the centre médian/parafascicular thalamic complex. This type of axon allows internal pallidal neurons to send efferent copies of the same information to the thalamus and brainstem and hence influence various neuronal systems scattered throughout the neuraxis. Pallidal information is conveyed to the cerebral cortex and the striatum via the thalamus, while it is projected back to different components of the basal ganglia via the numerous reentrant pathways that arise from the pedunculopontine nucleus. Virtually all neurons in the centre médian thalamic nucleus innervate massively the striatum and less prominently the primary motor cortex, which in turn projects to the striatum directly or via a collateral from long-range corticofugal pyramidal axons. The results call for a reappraisal of our current concept of the anatomical and functional organization of basal ganglia, which play a crucial role in sensorimotor integration. Our data indicate that basal ganglia and related thalamic nuclei form a widely distributed neuronal network, whose elements are endowed with a highly patterned set of axon collaterals. This morphological feature allows a complex and exquisitely precise interaction between the various basal ganglia and related thalamic nuclei. The elucidation of this finely tuned network is needed to understand the complex spatiotemporal sequence of neural events that ensures the flow of cortical information through the basal ganglia and thalamus.

Adult male Wistar rats were injected with 150/0.5, 75/1.5 and 50/2.0 mg/kg of pilocarpine (Pilo) and picrotoxin (PTX) (Pilo/PTX mg/kg). The vast majority of the animals developed status epilepticus (SE), after which they were observed for a period of 120–131 days for the occurrence of spontaneous recurrent seizures (SRS). After the experiments, animals were deeply anesthetized, perfused with a 10% formaldehyde fixative solution and their brains were processed with cresyl violet, Perls and Von Kossa techniques. Cell counts were performed under a regular microscopic grid in diverse anteroposterior levels of the thalamus. Several thalamic nuclei in the epileptic groups, particularly the central medial, central lateral, paracentral, mediodorsal, laterodorsal and lateroposterior, showed intense cell loss, pathologic calcification and iron tissue deposits. Our results are relevant to support the importance of the thalamus in the pathogenesis of the epilepsies.

It may soon be possible to adapt the use of deep brain stimulation (DBS) technologies developed to treat movement disorders to improve the general cognitive function of brain-injured patients. We outline neurophysiological foundations for novel neuromodulation strategies to address these goals. Emphasis is placed on developing a rationale for targeting the intralaminar and related nuclei of the human thalamus for electrical stimulation. Recent anatomical and physiological studies are compared with original neurophysiological recordings obtained in an alert non-human primate. In this context we consider neuronal mechanisms that may underlie both clinical observations and cognitive rehabilitation maneuvers that provide theoretical support for open and closed-loop strategies to remediate acquired cognitive disability (ACD).

Disruptions in the thalamocortical circuit have been related to several psychiatric disorders, such as schizophrenia and obsessive-compulsive disorders. The dopaminergic/GABAergic afferents to the limbic thalamocortical circuit originate in the ventral tegmental area (VTA) and play a crucial role in the regulation of the normal cognitive functions mediated by this circuit. Moreover, it has been shown that the dopaminergic modulatory system is altered in schizophrenics. Despite the strong clinical and behavioral evidence of the importance of the thalamocortical circuit and the mesocortical dopamine (DA) system for normal cognitive function, little is known about the basic synaptic interactions between the thalamus and VTA. This research hypothesized that VTA stimulation would evoke DAergic and/or GABAergic-mediated responses in the MD thalamic neurons. Using intracellular recordings in vivo, it was found that VTA stimulation evoked short latency EPSPs in 73% of the recorded MD neurons and IPSPs-like responses in 16% of the MD cells. The nature of the VTA-MD projection was explored using DAergic and GABAergic drugs. It was found that the indirect DAergic agonist amphetamine affects the spontaneous and VTA-mediated responses recorded in the MD thalamus. These results indicate that the VTA projection contributes to the modulation of MD activity and that the disruption of such modulation may be relevant in neuropsychiatry disorders.

A series of 49 cases with difficult to control seizures and non-candidates for ablation of the epileptic focus has been treated with electrical stimulation of the centromedian thalamic nuclei (ESCM).

Selected cases were: (1) epilepsia partialis continua (EPC) (n=5); (2) partial complex seizures (n=16); (3) bilateral frontal parasagittal seizures (n=6); (4) Lennox–Gastaut syndrome (n=22). All patients had four contact electrodes placed bilaterally through frontal parasagittal burr holes and guided by ventriculograms. Plotting of electrodes on sagittal and frontal sections of the Schaltenbrand and Bailey’s atlas permitted to determine their location. Electrodes were left externalized for periods of weeks to months to carry out the following tests. (1) Recordings of spontaneous seizures occurring during wakefulness and sleep. (2) Electrophysiological confirmation of their position by means of recruiting responses and desynchronization induced by low and high frequency stimulation. (3) Effects of high frequency stimulation on interictal and ictal activities. Electrodes were internalized and connected to a subcutaneous pulse generator programmed for alternating right and left ESCM 1 min ON and 4 min OFF at 60–130 Hz, 0.21–0.45 ms, 3–5 V forward and backward for 24 h per day. Repeated EEG recordings and a calendar of seizures were used for follow-up from 1 to 9 years.

CM paroxysmal discharges followed the initiation of seizures in cortical areas, occurred simultaneously with spike wave (SKW) complexes in cortical areas in Lennox–Gastaut syndrome and preceded the initiation of cortical SKW and clinical seizures in typical absences. Low frequency stimulation (6–8 cps) induced recruiting responses that were associated with those electrodes that produced best seizure control. Good to excellent results were obtained in cases of EPC and Lennox–Gastaut syndrome and on generalized tonic clonic convulsions (GTCs) and atypical absences (AA) with tonic or clonic components.

Consequently, we came to the conclusions that the CM participates in the propagation of most seizure types and also in the genesis of some of them and that ESCM is a safe and useful alternative for the treatment of some of the most difficult cases of uncontrollable seizures.

Thalamic afferents and efferents primarily use the neurotransmitter glutamate, which acts through a variety of ionotropic (NMDA, AMPA, kainate) and metabotropic receptors. The NMDAR is composed of multiple subunits, NR1 and NR2A-D. The obligatory NR1 subunit is expressed as one of eight isoforms, due to the alternative splicing of exons 5, 21, and 22. Each NR1 splice variant is functionally distinct. For instance, alternative splicing of exons 21 and 22 renders two C-terminal variants, which differentially associate with NR2 subunits and intracellular molecules such the PSD-95 family of proteins. These PSD proteins play a pivotal role in NMDAR function by linking NMDARs to the cytoskeleton and downstream signal-transducing enzymes that can directly modulate NMDAR function and/or promote NMDAR-associated intracellular events.

Previous work reported that NR1 is by far the most abundant NMDAR subunit expressed in the primate thalamus. In the current study, we extend these findings first by determining which NR1 isoforms are predominantly expressed in the thalamus. Secondly, we characterize the expression of the NMDAR-associated PSD molecules, such as PSD-95, in the thalamus. Using in situ hybridization, we examined expression of the transcripts encoding NR1 isoforms containing exons 5, 21, or 22, and transcripts encoding a set of the most well-characterized NMDAR-associated PSD proteins (NF-L, PSD93, PSD95, SAP102, and Yotiao). NR1 exon 22-containing isoforms are the most abundant subunit transcripts, accounting for 40–50% of the NR1 isoforms expressed in most thalamic nuclei. We also found that NF-L is by far the most abundant PSD protein expressed in the thalamus, followed by PSD-95, which is moderately and heterogeneously expressed. SAP102 and PSD-93 were expressed at moderate to low levels, with negligible amounts of Yotiao transcript expression. The PSD-95 family of molecules are critical for NMDAR function in the cell, and this study is the first to provide a detailed description of the expression of these molecules in primate thalamus. Our results demonstrate that NR1 splice variants and associated PSD proteins are heterogeneously expressed across the thalamus, which is likely related to the intracellular events that occur in different thalamic nuclei.

We examined the relationship between calbindin-D28k-defined subdivisions in the macaque inferior pulvinar and the patterns of afferent connections to cortical visual areas MT, V4 and V2. The subdivisions identified included the posterior (PIp), medial (PIm), central (PIc) and lateral (PI1) subdivisions. Projections to MT and V4 were largely segregated in the inferior pulvinar: projections to MT originated mainly from PIm, while projections to V4 originated mainly from PI1. In addition, weaker projections to MT were observed from PIp and PIc, and some projections from PIp to V4 were observed in one of two cases. Projections to V2 originated preferentially from PI1, with a lesser projection from PIc. No labeled cells were observed in PIm in five monkeys injected with various tracers into different regions of V2. Since most V2 injections were large enough to involve several neighboring stripe-like compartments, these findings suggest that PIm does not project to V2 compartments associated with neither dorsal nor ventral cortical processing streams. Cells projecting to V4 were not strictly segregated from those projecting to V2 in neither PI1 nor PIc, suggesting that inferior pulvinar projections do not map the position of visual areas in the cortical mantle.

This work is focused on the study of neuronal circuits arising from the rodent caudal intralaminar nuclei and their presumed role on basal ganglia function. Emphasis was placed on the analysis of the architecture of thalamostriatal and thalamo-subthalamic projections in albino rats. Our major interest was to elucidate whether thalamic inputs were related to projection neurons or local circuit neurons within targeted structures (striatum and subthalamic nucleus). Projections coming from the parafascicular nucleus (PF) to the striatum displayed a patchy organization throughout the matrix compartment. These patches are composed by dense terminal axonal arborizations, often containing striatal neurons projecting to the entopeduncular nucleus (ENT) (medial globus pallidus in primates) and neurons projecting to the substantia nigra reticulata (SNR). The thalamostriatal projections under scrutiny were also seen to be in register with all the major classes of striatal interneurons (nitrergic neurons, neurons containing the calcium binding protein parvalbumin (PV) and cholinergic interneurons). Subthalamic neurons projecting to the ENT are the presumed postsynaptic target for fibers coming from the sensorimotor part (dorsolateral) of the PF. In summary, glutamatergic axons arising from the PF might exert a dual control of the striatal output, either by directly exciting striatal projection neurons or indirectly by means of a previous synaptic contact onto an striatal interneuron which in turn modulates the activity of projection neurons. Furthermore, thalamic inputs can also gain access to basal ganglia output nuclei via subthalamo-pallidal projecting neurons, neurons receiving glutamatergic thalamo-subthalamic projections. Thus, activation of either circuit has an opposite physiological effect on the basal ganglia output nucleus. Taken together, these data suggest that the PF may influence neuronal activity in the direct and indirect circuits and could be considered as an additional component of the basal ganglia motor loops.