Thalamus & related systems最新文献

Intracellular recordings from thalamocortical (TC) neurons in the ventrolateral (VL) nucleus as well as paired intracellular recordings from TC-VL neurons and area 4 cortical neurons under ketamine–xylazine anesthesia were performed to study changes in hyperpolarization-rebound sequences evoked by successive stimuli to the dorsal thalamus at different frequencies and the impact of these changes at the cortical level. The cellular mechanisms of such changes in synaptic networks connecting TC with cortical neurons are relevant for short-term plasticity during low-frequency oscillatory activities. The progressive decrease in hyperpolarization of TC cells in response to single thalamic stimulus above a certain frequency (generally >1 Hz) and to pulse-trains at 10 Hz was mainly due to synaptic factors and not to mechanisms intrinsic to TC cells, as revealed by comparing responses evoked by synaptic volleys to those elicited by hyperpolarizing current pulses mimicking the synaptically evoked hyperpolarization-rebound sequence. The decreased hyperpolarization to repetitive synaptic volleys, leading to a decreased number of action potentials in the post-inhibitory spike-burst, had an impact on cortical activities, being matched by a decreased rebound depolarization of cortical cell during repetitive augmenting responses. The alterations in hyperpolarization-rebound sequences upon repetitive stimulation, probably resulting from the decreased efficacy of connections between thalamic reticular (RE) neurons to TC connections, results in the dampening of activities sustaining normal, and possibly paroxysmal, oscillations in the TC network. Our results suggest that this phenomenon should be taken into account when analyzing complex activities, such as physiological and pathological oscillations.

Neuroanatomical tracers were injected into two functionally distinct areas in the lateral sulcus of macaque monkeys, the parietal ventral area (PV) and the second somatosensory area (S2). Three of the four injection sites were electrophysiologically determined by defining the receptive fields of neurons at the injection site prior to the placement of the anatomical tracers. Additionally, all locations were confirmed myeloarchitectonically. Labeled cell bodies and axon terminals were identified in the ipsilateral dorsal thalamus and related to nuclear boundaries in tissue stained for cytochrome oxidase (CO) and Nissl substance. Our results indicate that PV receives substantial input from the inferior division of the ventral posterior nucleus (VPi), the anterior pulvinar (Pla), and from the ventral portion of the magnocellular division of the mediodorsal nucleus (MDm), which also is interconnected with prefrontal cortex, the entorhinal cortex and the amygdala. S2 receives input predominantly from VPi, the ventral posterior superior nucleus (VPs), and Pla. These results indicate that PV and S2 are involved in processing inputs from deep receptors in the muscles and joints. Because PV and S2 receive little if any cutaneous input from the thalamus, cutaneous input to these fields must arise mainly through cortical connections. Connectional data supports the proposition that PV and S2 integrate motor and somatic information necessary for proprioception, goal directed reaching and grasping and tactile object identification. Further, PV may play a role in tactile learning and memory.

These studies in fetal monkeys and ferrets show that the two fundamental types of thalamic GABA neuron populate the thalamus during widely separated developmental epochs. Those of the ventral thalamus (VT) and epithalamus (ET) appear very early in conjunction with the GABA cells of the substantia nigra, globus pallidus, and pretectum (PT). GABA neurons intrinsic to the dorsal thalamus (DT) appear later, long after proliferative activity has ceased in the wall of the third ventricle, after dorsal thalamic nuclei have differentiated and at the same time as principal neurons are acquiring a glutamatergic phenotype. The exact origins of the two waves of GABA cells are uncertain but some appear to arrive from extrinsic sources that include the ganglionic eminence (GE) of the basal forebrain.

Nucleus-specific expression of five gene transcripts related to the inhibitory, gamma-aminobutyric acid (GABA), neurotransmitter system (GABA_A receptor subunits α1, α5, β2, γ2, and 67 kDa glutamic acid decarboxylase (GAD₆₇)), and of seven transcripts related to the excitatory, glutamatergic, system (GluR2, 4–6, NR1 and NR2A, and α-type II calcium/calmodulin-dependent protein kinase (CAMKII-α)), were examined by quantitative in situ hybridization histochemistry in the thalami of brains from normal controls and from patients suffering from schizophrenia. Although there is evidence for cell loss and functional hypoactivity in the thalamus in schizophrenia, it was striking that quantitative levels and expression patterns of the transcripts studied showed only minor differences between schizophrenics and matched controls. Expression patterns of the transcripts had many similarities to the patterns seen in the thalamus of non-human primates. Abundant GABA_A-α1, GABA_A-β2, and GABA_A-γ2 subunit mRNAs levels were found in most nuclei. Expression levels of the NMDA receptor subunit, NR1, were higher than those seen for NR2A, AMPA (GluR2 and 4) or kainate (GluR5 and 6) receptor subunit mRNAs. Expression of NR2A mRNA was extremely low. CAMKII-α expression was restricted to glutamatergic neurons. Unlike in monkeys, GluR2 subunit mRNA expression was higher than GluR4 expression. These expression patterns form the beginning of a comprehensive database of patterns of gene expression at high resolution in the human forebrain in health and disease.

Voltage-sensitive dye imaging (VDI) of cortical activation patterns generated by electrical stimulation of thalamocortical afferents axons at different frequencies was studied, in vitro, using mouse brain slices. The study demonstrated that thalamocortical afferent axons stimulation could follow frequencies as high as 120 Hz without marked reduction. By contrast the power spectral density amplitude ratio in cortical layer 4 demonstrated a rapidly sigmoidal reduction at frequencies above 60 Hz. Similar findings were obtained with direct cortical afferent axons stimulation that obviated possible interactions at thalamic level. As pre-synaptic afferent field potentials, simultaneously recorded with the VDI at cortical level, followed higher stimulation frequency, it is concluded that cortical activity reduction is secondary to synaptic transmission failure. This interpretation agrees with the result from deep-brain stimulation (DBS) in humans in which high-frequency stimulation produces comparable therapeutic results, as does stereotaxic brain lesioning.

The companion paper (Llinás et al., 2001) presents evidence, at both cellular and network levels, for the role of resonant oscillatory thalamocortical properties in normal and pathological brain function. Here we present confirmatory single cell electrophysiology from the thalami of thalamocortical dysrhythmia (TCD) patients and review our surgical approach towards the relief of this chronic disabling condition, in its many forms. The goal of surgery is a rebalancing of the abnormal thalamocortical oscillation responsible for TCD. Our approach uses small strategically placed pre-thalamic and medial thalamic lesions that serve to make subcritical the low frequency thalamocortical reentry network attractor via desinhibition and desamplification. The lesions address classical and new stereotactic targets that provide therapeutic efficiency coupled with the sparing of the specific thalamocortical loops.

Data based on dual intracellular recordings from neocortical and thalamic neurons in anesthetized cats are presented to support the assumption that bisynaptic inhibition of thalamocortical (TC) neurons, induced by synchronous cortical volleys through a prior synaptic relay in GABAergic thalamic reticular (RE) neurons, may overcome the direct excitation of TC neurons. This effect occurs during cortical augmenting responses mimicking sleep spindles as well as during the self-sustained, post-augmenting activity. Although TC volleys directly produce cortical potentials, the cortex uses its own machinery to elaborate oscillatory responses that outlast thalamic stimuli, whereas, simultaneously, TC neurons remain under a prolonged hyperpolarization arising in RE neurons. This pattern suggests that, during slow-wave sleep, when TC neurons are unable to process faithfully fast recurring signals from the external world because of their inhibition, intracortical activity may underlie processes accounting for some forms of mental activity. Opposite activity patterns in cortical and TC neurons are also observed during spike-wave seizures, which are generated in cortex and are associated with steady inhibition in a majority of TC neurons. The inability of TC neurons to transfer signals from the outside world during spike-wave seizures may account for unconsciousness during absence (petit-mal) seizures.

Kainate receptors (KAR) remain the most poorly defined components of the glutamate receptor system in the CNS, mainly because of the difficulty of distinguishing currents gated by KAR from those mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor activation, and because KAR are expressed at significantly lower levels than AMPA receptors in most parts of the CNS.

The corticothalamic projection exerts its effects on thalamic neurons via NMDA, non-NMDA and metabotropic glutamate receptors. AMPA receptor mediated effects tend to predominate in the mature thalamus, but the involvement of kainate receptors at corticothalamic synapses on relay neurons and reticular nucleus neurons had not been studied.

The present work compared KAR influences on neurons in the ventral posterior nucleus (VP) and reticular nucleus (RTN), using whole-cell recording in P14–P20 mouse thalamocortical slices. The results were correlated with quantitative immuno-electron microscopic localization of kainate receptor sub-units at corticothalamic synapses in these nuclei. Small kainate-induced inward currents could be recorded in thalamic neurons in response to bath application of kainate, but no KAR-mediated pre-synaptic effects could be detected and no synaptic responses could be evoked in these cells by corticothalamic stimulation. Morphologically, GluR5/6/7 sub-units were expressed at low levels in both VP and RTN and were confined to post-synaptic membranes at corticothalamic synapses in both VP and RTN. Many synapses, however, lacked GluR5/6/7 immunoreactivity.

These results suggest that kainate receptor-mediated events are not major components of the responses of thalamic neurons to corticothalamic activation, either because of small numbers or their location in sites inaccessible to glutamate released from corticothalamic terminals.

The effect of chronic high frequency deep brain stimulation (DBS) on rest tremor was investigated in subjects with Parkinson’s disease (PD). Eight PD subjects with high amplitude tremor (Group 1) and eight PD subjects with low amplitude tremor (Group 2, used as a reference group) were examined by a clinical neurologist and tested with a velocity laser to quantify time and frequency domain characteristics of tremor. Possible rebound effects in rest tremor when DBS was stopped for 60 min were also explored. Participants received DBS of the internal globus pallidus (GPi) (n=7), the subthalamic nucleus (STN) (n=6) or the ventrointermediate nucleus of the thalamus (Vim) (n=3). Tremor was recorded with a velocity laser under two conditions of DBS (on–off) and two conditions of medication (l-Dopa on–off). Correlations between clinical and experimental results for tremor amplitude was 0.70 with no medication and no stimulation. In Group 1, DBS decreased tremor amplitude but also increased spectral concentration and median frequency significantly. Under medication, the changes in tremor with and without stimulation were not statistically significant (Group 1). When stimulation was stopped for 60 min, a rebound in tremor amplitude was observed and median frequency remained stable in Group 1. None of the comparisons examined produced significant effects in Group 2. Taken together, these results suggest that beyond its effect on tremor amplitude DBS acted also on tremor frequency and did not modify tremor characteristics in subjects with low amplitude tremor.

An atlas of serial sections stained alternately for one of the three calcium-binding proteins, calbindin, calretinin or parvalbumin, or for markers that demarcate borders of thalamic nuclei in and around the posterior pole of the ventral posterior thalamic nucleus of a macaque monkey is presented. The concentrated focal zone of calbindin-immunoreactive fiber ramifications considered by others to form a specific pain and temperature relay nucleus is shown to be located entirely within the confines of the ventral posterior medial (VPM) nucleus. It contains a large population of calbindin-immunoreactive cells and overlaps a region of dense cell and fiber immunoreactivity for parvalbumin. In other parts of the ventral posterior complex, calbindin and parvalbumin immunoreactivity is complementary rather than co-extensive. It is unlikely that the zone of intense calbindin immunoreactivity in VPM forms the only thalamic relay for noxious thermal and mechanical inputs to the cerebral cortex.