Functional correlation of GABA(A) receptor alpha subunits expression with the properties of IPSCs in the developing thalamus.
(1/21)
GABA(A) receptor alpha1 and alpha2 subunits are expressed differentially with ontogenic period in the brain, but their functional roles are not known. We have recorded GABA(A) receptor-mediated IPSCs from laterodorsal (LD) thalamic relay neurons in slices of rat brain at various postnatal ages and found that decay times of evoked IPSCs and spontaneous miniature IPSCs undergo progressive shortening during the first postnatal month. With a similar time course, expression of transcripts and proteins of GABA(A) receptor alpha2 subunit in LD thalamic region declined, being replaced by those of alpha1 subunit. To further address the causal relationship between alpha subunits and IPSC decay time kinetics, we have overexpressed GABA(A) receptor alpha1 subunit together with green fluorescent protein in LD thalamic neurons in organotypic culture using recombinant Sindbis virus vectors. Miniature IPSCs recorded from the LD thalamic neurons overexpressed with alpha1 subunit had significantly faster decay time compared with control expressed with beta-galactosidase. We conclude that the alpha2-to-alpha1 subunit switch underlies the developmental speeding in the decay time of GABAergic IPSCs. (+info)
Muscarinic regulation of dendritic and axonal outputs of rat thalamic interneurons: a new cellular mechanism for uncoupling distal dendrites.
(2/21)
Inhibition is crucial for sharpening the sensory information relayed through the thalamus. To understand how the interneuron-mediated inhibition in the thalamus is regulated, we studied the muscarinic effects on interneurons in the lateral posterior nucleus and lateral geniculate nucleus of the thalamus. Here, we report that activation of muscarinic receptors switched the firing pattern in thalamic interneurons from bursting to tonic. Although neuromodulators switch the firing mode in several other types of neurons by altering their membrane potential, we found that activation of muscarinic subtype 2 receptors switched the fire mode in thalamic interneurons by selectively decreasing their input resistance. This is attributable to the muscarinic enhancement of a hyperpolarizing potassium conductance and two depolarizing cation conductances. The decrease in input resistance appeared to electrotonically uncouple the distal dendrites of thalamic interneurons, which effectively changed the inhibition pattern in thalamocortical cells. These results suggest a novel cellular mechanism for the cholinergic transformation of long-range, slow dendrite- and axon-originated inhibition into short-range, fast dendrite-originated inhibition in the thalamus observed in vivo. It is concluded that the electrotonic properties of the dendritic compartments of thalamic interneurons can be dynamically regulated by muscarinic activity. (+info)
Immediate and long term outcome after infrathalamic and thalamic lesioning for intractable Tourette's syndrome.
(3/21)
OBJECTIVE: The surgical treatment of intractable Tourette's syndrome is controversial. Experience with 17 consecutive patients treated between 1970 and 1998 is reviewed and the efficacy and safety of surgical treatment is assessed. METHODS: These patients were retrospectively reclassified into subtypes according to the protocol of the Tourette's Syndrome Study Group. One patient was excluded from the study. Ventriculography based stereotactic zona incerta (ZI) and ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all patients. The preoperative, postoperative, and late tic severities were assessed by the tic severity rating scale. The median follow up of 11 patients (65%) was 7 years (range 3.5-17 years) and six patients were lost to long term follow up. RESULTS: Median age was 23 years (range 11-40) at the time of surgery. Median duration of illness was 14 years (range 3-33). The mean preoperative motor and vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66), respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry of symptoms provide an effective control of tic severity (p motor and vocal<0.001). In attenuation of contralateral symptoms, a second surgical intervention in the relevant side could reduce tic severity sufficiently (p motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients. Only one permanent complication was registered in six patients followed up after unilateral surgery. Two out of five patients followed up after bilateral surgery had disabling side effects of surgery. CONCLUSIONS: ZI and VL/LM lesioning provide a significant long term reduction of tic severity in intractable Tourette's syndrome. Adequate selection of the side of first intervention might prevent the patient from increased risk of bilateral surgery. (+info)
Activation of thalamic ventroposteriolateral neurons by phrenic nerve afferents in cats and rats.
(4/21)
It has been demonstrated that phrenic nerve afferents project to somatosensory cortex, yet the sensory pathways are still poorly understood. This study investigated the neural responses in the thalamic ventroposteriolateral (VPL) nucleus after phrenic afferent stimulation in cats and rats. Activation of VPL neurons was observed after electrical stimulation of the contralateral phrenic nerve. Direct mechanical stimulation of the diaphragm also elicited increased activity in the same VPL neurons that were activated by electrical stimulation of the phrenic nerve. Some VPL neurons responded to both phrenic afferent stimulation and shoulder probing. In rats, VPL neurons activated by inspiratory occlusion also responded to stimulation on phrenic afferents. These results demonstrate that phrenic afferents can reach the VPL thalamus under physiological conditions and support the hypothesis that the thalamic VPL nucleus functions as a relay for the conduction of proprioceptive information from the diaphragm to the contralateral somatosensory cortex. (+info)
Microinjection of adrenomedullin into rostral ventrolateral medulla increases blood pressure, heart rate and renal sympathetic nerve activity in rats.
(5/21)
The present study was undertaken to examine the effects of microinjection of adrenomedullin (AM) into rostral ventrolateral medulla (RVLM) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in 34 anesthetized Sprague-Dawley rats. The results obtained are as follows. (1) Following microinjection of AM (10 micromol/L, 200 nl) into the RVLM, MAP, HR and RSNA were significantly increased from 99.09+/-3.32 mmHg, 370.78+/-7.84 bpm and 100+/-0% to 113.57+/-3.64 mmHg (P>0.001), 383.28+/-7.38 bpm (P>0.001) and 123.72+/-2.74% (P>0.001), respectively. (2) Pretreatment with microinjection of calcitonin gene-related peptide receptor antagonist CGRP8-37 (100 micromol/L, 200 nl) did not change the effects of AM. (3) L-arginine (100 mg/kg, 0.2 ml, i.v.), an NO precursor, abolished the effects of AM. This study demonstrates that AM acting at the rostral ventrolateral medulla may produce significant cardiovascular responses, the effects are not mediated by CGRP receptor but may be abolished by NO. (+info)
Distinct firing properties of higher order thalamic relay neurons.
(6/21)
It has been proposed that the thalamus is composed of at least two types of nuclei. First-order relay nuclei transmit signals from the periphery to the cortex while higher order nuclei may route information from one cortical area to another. Although much is known about the functional properties of relay neurons in first-order nuclei, little is known about relay neurons belonging to higher-order nuclei. We investigated the electrophysiological properties of relay cells in a higher-order thalamic nucleus using in vitro intracellular recordings from thalamic slices of the rat's lateral posterior nucleus (LPN). We found neurons of the LPN possess many of the same membrane properties as first-order relay neurons. These included low-threshold calcium spikes (IT) and burst firing, a mixed cation conductance (IH) that prevented membrane hyperpolarization, and a transient K+ conductance that delayed spike firing (IA). The repetitive firing characteristics of LPN neurons were more distinct. One group of cells, located in the more caudal regions of the LPN responded to depolarizing current pulses with a train of action potentials or in a regular spiking (RS) mode. This form of firing showed a steep but highly linear increase in firing frequency with increasing levels of membrane depolarization. Another group of cells, located in the more rostral regions of the LPN, responded to depolarizing current pulses with clusters of high-frequency bursts or in a clustered spiking (CS) mode. The overall firing frequency rose nonlinearly with membrane depolarization, but the frequency of a given burst remained relatively constant. The caudal LPN receives input from the superior colliculus, whereas the rostral LPN receives input from layers V and VI of the visual cortex. Thus the RS and CS cells may be driven by subcortical and cortical inputs respectively, and the distinct temporal properties of their response modes may be a necessary component of the LPN circuitry. (+info)
Medial lateral extent of thermal and pain sensations evoked by microstimulation in somatic sensory nuclei of human thalamus.
(7/21)
We explored the region of human thalamic somatic sensory nucleus (ventral caudal, Vc) with threshold microstimulation during stereotactic procedures for the treatment of tremor (124 thalami, 116 patients). Warm sensations were evoked more frequently in the posterior region than in the core. Proportion of sites where microstimulation evoked cool and pain sensations was not different between the core and the posterior region. In the core, sites where both thermal and pain sensations were evoked were distributed similarly in the medial two planes and the lateral plane. In the posterior region, however, warm sensations were evoked more frequently in the lateral plane (10.8%) than in the medial planes (3.9%). No mediolateral difference was found for sites where pain and cool sensations were evoked. The presence of sites where stimulation evoked taste or where receptive and projected fields were located on the pharynx were used as landmarks of a plane located as medial as the posterior part of the ventral medial nucleus (VMpo). Microstimulation in this plane evoked cool, warm, and pain sensations. The results suggest that thermal and pain sensations are processed in the region of Vc as far medial as VMpo. Thermal and pain sensations seem to be mediated by neural elements in a region likely including the core of Vc, VMpo, and other nuclei posterior and inferior to Vc. (+info)
Differential responses in three thalamic nuclei in moderately disabled, severely disabled and vegetative patients after blunt head injury.
(8/21)
In vivo imaging techniques have indicated for many years that there is loss of white matter after human traumatic brain injury (TBI) and that the loss is inversely related to cognitive outcome. However, correlated, quantitative evidence for loss of neurons from either the cerebral cortex or the diencephalon is largely lacking. There is some evidence in models of TBI that neuronal loss occurs within the thalamus, but no systematic studies of such loss have been undertaken in the thalamus of humans after blunt head injury. We have undertaken a stereological analysis of changes in numbers of neurons within the dorsomedial, ventral posterior and lateral posterior thalamic nuclei in patients assessed by the Glasgow Outcome Scale as moderately disabled (n = 9), severely disabled (n = 12) and vegetative (n = 10) head-injured patients who survived between 6 h and 3 years, and controls (n = 9). In histological sections at the level of the lateral geniculate body, the cross-sectional area of each nucleus and the number and the mean size of neurons within each nucleus was quantified. A statistically significant loss of cross-sectional area and number of neurons occurred in the dorsomedial nucleus in moderately disabled, and both the dorsomedial and ventral posterior thalamic nuclei in severely disabled and vegetative head-injured patients. However, there was no change in neuronal cell size. In the lateral posterior nucleus, despite a reduction in mean cell size, there was not a significant change in either nuclear area or number of neurons in cases of moderately disabled, severely disabled or vegetative patients. We posit, although detailed neuropsychological outcome for the patients included within this study was not available, that neuronal loss in the dorsomedial thalamus in moderately and severely disabled and vegetative patients may be the structural basis for the clinical assessment in the Glasgow Outcome Scale. In severely disabled and vegetative patients, loss of neurons from the ventral posterior thalamic nucleus may also reflect loss of response to afferent stimuli. (+info)