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PubMed2005

Dopaminergic control of local interneuron activity in the thalamus.

The dorsal lateral geniculate nucleus (dLGN), the major thalamic station of the visual pathway, contains a fairly large number of dopaminergic terminals, and dopamine was found to reduce spontaneous and visually evoked activity in the dLGN in vivo. The cellular basis of this influence remained unknown. Here we have used whole cell patch-clamp techniques to analyse the effects of dopamine (DA) on GABAergic transmission in dLGN slices of juvenile postnatal day (P) 12-P24 Long-Evans rats or juvenile (P12-P22) GAD67-GFP (Deltaneo) mice. Spontaneous inhibitory postsynaptic currents (sIPSCs) were increased in frequency by the D(2)-like agonist quinpirole (QUIN) in rat (n = 6), as well as in mouse (n = 5) thalamic slices. This effect was blocked in the presence of the D(2)-like antagonist sulpiride (SULP, n = 5) and was absent in the ventrobasal complex (VB) of rat (n = 7) and mouse (n = 4) thalamus, which is devoid of GABAergic interneurons. Direct recordings from labelled GABAergic neurons in the dLGN of GAD67-GFP mice revealed a QUIN-mediated membrane depolarization (n = 12), which was attenuated by SULP (n = 6). These data demonstrate that DA through activation of D(2)-like receptors in GABAergic interneurons induces an increase in inhibitory interactions most likely at F2 dendrodendritic terminals, thereby providing a cellular correlate of the observation made in vivo that DA predominantly acts through inhibition of relay cell activity in the dLGN.

Animals↗
PubMed2005

Opposite effects of tetanic stimulation of the auditory thalamus or auditory cortex on the acoustic startle reflex in awake rats.

The amygdala mediates both emotional learning and fear potentiation of startle. The lateral amygdala nucleus (LA) receives auditory inputs from both the auditory thalamus (medial geniculate nucleus; MGN) and auditory association cortex (AAC), and is critical for auditory fear conditioning. The central amygdala nucleus, which has intra-amygdaloid connections with LA, enhances startle magnitude via midbrain connections to the startle circuits. Tetanic stimulation of either MGN or AAC in vitro or in vivo can induce long-term potentiation in LA. In the present study, behavioural consequences of tetanization of these auditory afferents were investigated in awake rats. The acoustic startle reflex of rats was enhanced by tetanic stimulation of MGN, but suppressed by that of AAC. All the tetanization-induced changes of startle diminished within 24 h. Blockade of GABAB receptors in the LA area reversed the suppressive effect of tetanic stimulation of AAC on startle but did not change the enhancing effect of tetanic stimulation of MGN. Moreover, transient electrical stimulation of MGN enhanced the acoustic startle reflex when it lagged behind acoustic stimulation, but inhibited the acoustic startle reflex when it preceded acoustic stimulation. The results of the present study indicate that MGN and AAC afferents to LA play different roles in emotional modulation of startle, and AAC afferents are more influenced by inhibitory GABAB transmission in LA.

Acoustic Stimulation↗
PubMed2005

Differential modulation of anterior cingulate cortical activity by afferents from ventral tegmental area and mediodorsal thalamus.

A distinct increase in cell firing activity is reported in prefrontal cortex during working memory tasks. The afferents that modulate this activity are not yet identified. Using in vivo intracellular recording and labelling of prefrontal cortical pyramidal neurons in anaesthetized rats, we systematically evaluated the influences of afferent projections arising from the ventral tegmental area (VTA) and mediodorsal thalamus (MD) by phasic electrical stimulation with a range of stimulus frequencies. Both VTA- and MD-responsive pyramidal neurons exhibited extensive intracortical axon arborization. Neither single shocks to the VTA at 0.2 Hz, nor low frequency trains of stimuli at 1-4 Hz (< 5 Hz) interrupted the periodicity of membrane bistability in bistable pyramidal neurons. However, high-frequency VTA-train stimulation (10-50 Hz) interrupted the bistability, and produced sustained membrane depolarizations accompanied by intense tonic firing in a frequency-dependent manner. Electrical stimulation of MD (10-50 Hz) did not produce sustained activity in the same PFC neurons. Thus, the sustained activity induced by high-frequency VTA trains is input selective. This effect of VTA-train stimulation was attenuated by systemic injection of the D1 receptor antagonist, SCH 23390, and blocked by acute dopamine (DA) depletion produced via alpha-methyl-para-tyrosine pre-treatment, suggesting that sustained cortical activity is mediated by DA. Chemical stimulation of VTA via intra-VTA infusion of NMDA induced sustained activity similar to VTA-train stimulation. Thus, while both VTA- and MD-responsive pyramidal neurons exhibited extensive intracortical axon arborization, VTA synapses (as opposed to MD synapses) may be critically positioned in the dendritic arborizations of anterior cingulate cortical pyramidal neurons, which may allow their modulation of sustained activity in prefrontal bistable neurons.

Action Potentials↗
PubMed1997

The electrogenic effects of Na(+)-K(+)-ATPase in rat auditory thalamus.

1. The electrogenic effects of the Na(+)-K(+)-ATPase in thalamic neurones were investigated by means of intracellular and whole-cell patch-clamp recording techniques in rat medial geniculate body (MGB) maintained in vitro. 2. In twenty-six out of thirty-one neurones recorded intracellularly, application of the Na(+)-K+ pump inhibitor strophanthidin induced two different types of membrane depolarization: a small, reversible depolarization with a peak amplitude of 4 +/- 2.6 mV or a prolonged depolarization of large amplitude (48.6 +/- 9.0 mV) with or without a decrease in apparent membrane resistance. Blockade of glutamate receptors with kynurenic acid or 6-cyano-7-nitroquinoxaline-2,3-dione and (+/-)-2-amino-5-phosphonopentanoic acid did not prevent either type of pump response, but the large depolarization was not seen when the medium contained the sodium channel blocker TTX. 3. Whole-cell patch-clamp recording showed that the small membrane depolarization is mediated by an inward membrane current (39.00 +/- 5.70 pA) that exhibited a weak voltage dependence. An inward current of similar amplitude was also induced in MGB cells when the pipette solution contained nominally zero Na+ or when K+ was temporarily omitted from the extracellular medium. The large membrane depolarization or the corresponding membrane current was not observed in whole-cell conditions. 6. Transient inhibition of the electrogenic Na(+)-K(+)-ATPase consistently led to a change in the mode of synaptic transmission in MGB cells, during which the synaptically evoked burst response was either blocked or converted into a single spike discharge. 7. Taken together, these data suggest that blockade of the electrogenic pump produces a dual membrane effect in mammalian thalamic neurones: a small electrogenic membrane depolarization and a large depolarization response that can be prevented by artificially maintaining the transmembrane ionic gradients. The electrogenic activity of the Na(+)-K(+)-ATPase may play an important role in setting the mode of synaptic transmission in sensory thalamus.

Animals↗
PubMed2006

Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats increases seizure frequency.

PURPOSE: Electrical stimulation of the anterior nucleus of the thalamus (ANT) is receiving increased attention as a novel means of controlling intractable epilepsy, and has entered human clinical trial. Animal data supporting the anticonvulsant benefit of ANT stimulation, however, has been obtained from acute chemoconvulsant models of epilepsy rather than models of chronic epilepsy with spontaneous seizures. It is unknown whether ANT stimulation is effective in models of chronic epilepsy. METHODS: Bilateral ANT stimulation was evaluated in rats with chronic epilepsy following acute status epilepticus (SE) produced by systemic kainic acid (KA) administration. The evolution of epilepsy following KA SE and the effects of ANT stimulation were monitored by continuous video-EEG. RESULTS: Following KA SE, most rats have 2-8 seizures per day, and the average seizure rate increases over time, doubling over the course of 14 weeks. Behavioral seizure severity, after the initial development of epilepsy, remains stable. Seizure frequency during ANT stimulation was 2.5 times the baseline seizure frequency. In some cases stimulation triggered seizures were observed. The effects of stimulation were specific to the ANT. Stimulation applied to electrodes placed outside the ANT did not significantly worsen seizure frequency. CONCLUSIONS: ANT stimulation exacerbated seizure frequency in rats with chronic epilepsy following kainate status epilepticus.

Acute Disease↗
PubMed1971

Spontaneous and evoked activity of neurones in the somatosensory thalamus of the waking cat.

1. Adult cats were prepared for chronic micro-electrode recording in the nucleus ventralis posterolateralis (VPL) of the ventrobasal complex (VB) of the thalamus. Spontaneous and evoked activity of single neurones was recorded extracellularly while the animal stood in a hammock. The behavioural state of the animal and the electroencephalogram (e.e.g.) were observed and recorded.2. Three hundred and twenty-five single neurones sensitive to movement of hairs, depression of skin or movement of claws were isolated and studied. Peripheral receptive fields were on the contralateral surface of the body. They remained constant in size and location over long periods of time and despite changes in the behavioural state of the animal. Most of the receptive fields covered a cutaneous area at least as large as an entire paw and many covered an entire limb and extended on to the trunk. These fields are larger than those described by other investigators using natural stimulation in anaesthetized or paralysed animals.3. Moving hairs or touching skin in the peripheral receptive field elicited a burst of spikes at frequencies between 100 and 150/sec. Repeated stimulation did not result in obvious alteration or habituation of the response. There was no apparent change in responsiveness of neurones to peripheral stimulation when the animal was asleep.4. Except for claw-sensitive units, all neurones were active in the absence of intentional stimulation of the receptive field. When the animals were awake, VPL neurones fired more regularly than during sleeping. In slow sleep, with e.e.g. slow waves and spindles, firing patterns were characterized by the presence of more high-frequency bursts of spikes and more long interspike intervals than in waking. Claw-sensitive units, silent during waking, fired in bursts during sleep. When small doses of barbiturate were injected intravenously while recording the activity of neurones, the firing pattern changed to one in which all of the activity occurred in the form of high-frequency bursts. Interburst intervals were variable.5. The level of spontaneous activity in VB in conscious cats is greater than in sensory and sensorimotor cortex to which it projects. The pronounced effect of behavioural state on spontaneous activity of these neurones suggests that the background activity in somatosensory systems may play some role in the processing of afferent input.

Action Potentials↗
PubMed1980

The discharges during movement of cells in the ventrolateral thalamus of the conscious monkey.

1. Monkeys were trained to perform a stereotyped movement task in return for food rewards. On completion of training a headpiece which allowed microelectrode access to the thalamus for single cell recordings during performances of the task was attached at a surgical operation. The location of each cell studied was determined by histological examination of the fixed brain and precise identification of electrode tracks. 2. Ninety-three of ninety-seven cells discharging in association with arm movements but not responding to natural activation of peripheral receptors in the forelimb were located predominantly in the rostral part of nucleus VPLo and the caudo-ventral part of VLo. These cells appeared to be associated with active movement in one direction of a specific joint. 3. 52% of these 'motor' cells discharged in association with movements of either forelimb. The other 48% discharged in association with movement of the contralateral arm and hand only. 4. Sixty cells responded to stimulation of deep receptors or to passive limb manipulation in the relaxed and cooperative animal. These cells were predominantly located in the ventro-caudal part of VPLo and all the responses were obtained from contralateral receptors. Their discharges during performances of the motor task were indistinguishable from those of 'motor' cells. 5. Ninety-two cells were driven by limb manipulation and by natural activation of superficial cutaneous receptors and these were found predominantly in VPLo and VPLc. All responses were from contralateral receptors. These cells discharged during performance of the motor task; for some of them, their afferent input zones were not being stimulated by contact with the manipulandum when their 'motor' discharges commenced. 6. Although responses in each of the above groups of cells were sought by imposing a sudden perturbation of the limb during the performance of the active movement task, no responses were seen.

Action Potentials↗
PubMed2005

Complementary process to response bias in the centromedian nucleus of the thalamus.

Activity in several areas of the human brain and the monkey brain increases when a subject anticipates events associated with a reward, implicating a role for bias of decision and action. However, in real life, events do not always appear as expected, and we must choose an undesirable action. More than half of the neurons in the monkey centromedian (CM) thalamus were selectively activated when a small-reward action was required but a large-reward option was anticipated. Electrical stimulation of the CM after a large-reward action request substituted a brisk performance with a sluggish performance. These results suggest involvement of the CM in a mechanism complementary to decision and action bias.

Animals↗
PubMed2005

Long-term modulation of electrical synapses in the mammalian thalamus.

Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus.

Action Potentials↗
PubMed1988

Experimentally induced visual projections into auditory thalamus and cortex.

Retinal cells have been induced to project into the medial geniculate nucleus, the principal auditory thalamic nucleus, in newborn ferrets by reduction of targets of retinal axons in one hemisphere and creation of alternative terminal space for these fibers in the auditory thalamus. Many cells in the medial geniculate nucleus are then visually driven, have large receptive fields, and receive input from retinal ganglion cells with small somata and slow conduction velocities. Visual cells with long conduction latencies and large contralateral receptive fields can also be recorded in primary auditory cortex. Some visual cells in auditory cortex are direction selective or have oriented receptive fields that resemble those of complex cells in primary visual cortex. Thus, functional visual projections can be routed into nonvisual structures in higher mammals, suggesting that the modality of a sensory thalamic nucleus or cortical area may be specified by its inputs during development.

Afferent Pathways↗
PubMed1974

Nucleus dorsalis superficialis (lateralis dorsalis) of the thalamus and the limbic system in man.

Although the earlier supposition was that the n. dorsalils superficialis (n. lateralis dorsalis) of the thalamus projected to the parietal region, more recent evidence has linked it to the posterior cingulate gyrus and possibly adjacent regions near the splenium of the corpus callosum. An afferent supply from lower levels was in more doubt, although some report had been made of cell and fibre degeneration in the n. dorsalis superficialis after extensive temporal resections and section of the fornix in lower primates. The five human hemispheres of the present study all had lesions of long duration below the level of the splenium of the corpus callosum in the posteromedial temporal region. All showed marked degeneration in the fornix and n. dorsalis superficialis. In favourably stained cases, gliotic fascicles could be followed from the descending column of the fornix to the n. dorsalis superficialis via the region lateral to the stria medullaris thalami. The cell loss in the nucleus thus appeared to be an instance of anterograde transynptic degeneration. These cases provided an interesting instance in which human infarctions provided natural lesions that would have been hard to duplicate in experimental animals.

Basal Ganglia↗
PubMed1986

Limb apraxia in patients with damage confined to the left basal ganglia and thalamus.

Limb apraxia was investigated with standardised tests in 14 patients whose CT scan provided evidence of a vascular lesion confined to the left basal ganglia, or the thalamus, or both, and not involving the cortex or adjacent white matter. Five patients were severely impaired in imitating movements and pantomiming object use. Four of them also performed poorly when tested with real objects. In two patients the lesion was primarily thalamic and in three the lesion was primarily in the lenticular nucleus and the posterior limb of the internal capsule. Patients without apraxia generally had smaller injuries, but there were exceptions. Apraxia is currently conceived of as due to damage of cortical areas and their cortico-cortical connections, but the present data suggest that the model should be enlarged to include the deep nuclei and the pathways running through them.

Aged↗
PubMed2003

Dissociation of spatial-, object-, and sound-coding neurons in the mediodorsal nucleus of the primate thalamus.

The mediodorsal nucleus (MD) is the thalamic gateway to the prefrontal cortex, an area of the brain associated with spatial and object working memory functions. We have recorded single-neuron activities from the MD nucleus in monkeys trained to perform spatial tasks with peripheral visual stimuli and a nonspatial task with foveally presented pictures of objects and faces-tasks identical to those we have previously used to map regional specializations in the dorso- and ventro-lateral prefrontal cortex, respectively. We found that MD neurons exhibited categorical specificity-either responding selectively to locations in the spatial tasks or preferentially to specific representations of faces and objects in the nonspatial task. Spatially tuned neurons were located in parts of the MD connected with the dorsolateral prefrontal cortex while neurons responding to the identity of stimuli mainly occupied more ventral positions in the nucleus that has its connections with the inferior prefrontal convexity. Neuronal responses to auditory stimuli were also examined, and vocalization sensitive neurons were found in more posterior portions of the MD. We conclude that MD neurons are dissociable by their spatial and nonspatial coding properties in line with their cortical connections and that the principle of information segregation in cortico-cortical pathways extends to the "association" nuclei of the thalamus.

Acoustic Stimulation↗
PubMed2005

Vagal-evoked activity in the parafascicular nucleus of the primate thalamus.

The physiological effects of ascending vagal afferent activity in the primate forebrain have not been established, and because vagus nerve stimulation (VNS) is useful clinically for treatment of epilepsy and depression, these actions need to be identified. We used a roving microelectrode to record vagal-evoked potentials in the thalamus of the macaque monkey. In addition to the anticipated activation in the gustatory/visceral thalamic relay nucleus, we found an unexpectedly larger and earlier response focus with multi-unit discharges in the adjacent parafascicular nucleus. These data reveal a potent vagal input to this intralaminar nucleus, which is normally considered to be involved in motor control. This finding indicates that a role for this vagal activation site in the anti-epileptic effects of VNS needs to be considered.

Animals↗
PubMed2003

What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus.

Neuronal processing in cerebral cortex and signal transmission from cortex to brain stem have been studied extensively, but little is known about the numerous feedback pathways that ascend from brain stem to cortex. In this study, we characterized the signals conveyed through an ascending pathway coursing from the superior colliculus (SC) to the frontal eye field (FEF) via mediodorsal thalamus (MD). Using antidromic and orthodromic stimulation, we identified SC source neurons, MD relay neurons, and FEF recipient neurons of the pathway in Macaca mulatta. The monkeys performed oculomotor tasks, including delayed-saccade tasks, that permitted analysis of signals such as visual activity, delay activity, and presaccadic activity. We found that the SC sends all of these signals into the pathway with no output selectivity, i.e., the signals leaving the SC resembled those found generally within the SC. Visual activity arrived in FEF too late to contribute to short-latency visual responses there, and delay activity was largely filtered out in MD. Presaccadic activity, however, seemed critical because it traveled essentially unchanged from SC to FEF. Signal transmission in the pathway was fast ( approximately 2 ms from SC to FEF) and topographically organized (SC neurons drove MD and FEF neurons having similarly eccentric visual and movement fields). Our analysis of identified neurons in one pathway from brain stem to frontal cortex thus demonstrates that multiple signals are sent from SC to FEF with presaccadic activity being prominent. We hypothesize that a major signal conveyed by the pathway is corollary discharge information about the vector of impending saccades.

Animals↗
PubMed2004

Receptive field size and response latency are correlated within the cat visual thalamus.

Each point in visual space is encoded at the level of the thalamus by a group of neighboring cells with overlapping receptive fields. Here we show that the receptive fields of these cells differ in size and response latency but not at random. We have found that in the cat lateral geniculate nucleus (LGN) the receptive field size and response latency of neighboring neurons are significantly correlated: the larger the receptive field, the faster the response to visual stimuli. This correlation is widespread in LGN. It is found in groups of cells belonging to the same type (e.g., Y cells), and of different types (i.e., X and Y), within a specific layer or across different layers. These results indicate that the inputs from the multiple geniculate afferents that converge onto a cortical cell (approximately 30) are likely to arrive in a sequence determined by the receptive field size of the geniculate afferents. Recent studies have shown that the peak of the spatial frequency tuning of a cortical cell shifts toward higher frequencies as the response progresses in time. Our results are consistent with the idea that these shifts in spatial frequency tuning arise from differences in the response time course of the thalamic inputs.

Action Potentials↗
PubMed2003

Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats.

Extracellular action potentials were recorded from 73 neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of the whole oral cavity. The stimulus array consisted of 16 room-temperature (23 degrees C) sapid stimuli, distilled water at three temperatures (0, 23, and 37 degrees C), and 0.1 M NaCl at three temperatures (0, 23, and 37 degrees C). Among all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to taste and temperature, none to taste and touch, but 6% to all three modalities. Discharge rates evoked by the basic tastants were 13.8 +/- 1.6 (SD) spikes/s for 0.1 M NaCl, 9.3 +/- 1.4 spikes/s for 0.01 M HCl, 5.1 +/- 0.9 spikes/s for 0.5 M sucrose, and 4.3 +/- 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean responses at 0, 23, and 37 degrees C of 9.9 +/- 1.5, 0.6 +/- 0.4, and 1.3 +/- 0.9 spikes/s, respectively. The mean firing rate evoked by 37 and 0 degrees C NaCl was 15.0 +/- 2.4 and 17.0 +/- 2.8 spikes/s, respectively. The exponent of the NaCl concentration-response power function was 0.39. Thalamic taste cells were broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory cells was 0.79 +/- 0.02. Two cells responded predominantly with inhibition, which accounted for the majority of inhibitory responses. The taste neurons were statistically divisible into three groups: sodium-oriented (n = 40), acid-oriented (n = 12), and sugar-oriented (n = 17). Four additional bitter-oriented neurons were not closely enough related to be defined as a group and were considered outliers. The sodium-oriented group could be divided into three statistically distinct subgroups, differing in the specificity of their responses to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response rates, signal-to-noise ratio, proportions of cells responding best to basic tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc neurons have characteristics that are intermediate between those of parabrachial and cortical gustatory neurons.

Action Potentials↗
PubMed2004

Neuronal activity throughout the primate mediodorsal nucleus of the thalamus during oculomotor delayed-responses. II. Activity encoding visual versus motor signal.

We collected single-neuron activity from the mediodorsal (MD) nucleus of the thalamus, examined the information that was represented by task-related activity during performance of a spatial working memory task, and compared the present results with those obtained in the dorsolateral prefrontal cortex (DLPFC). We used two oculomotor delayed-response (ODR) tasks. In the ordinary ODR task, monkeys were required to make a memory-guided saccade to the location where a visual cue had been presented 3 s previously, whereas in the rotatory ODR task, they were required to make a memory-guided saccade 90 degrees clockwise from the cue direction. By comparing the best directions of the same task-related activity between the two tasks, we could determine whether this activity represented the cue location or the saccade direction. All cue-period activity represented the cue location. In contrast, 56% of delay-period activity represented the cue location and 41% represented the saccade direction. Almost all response-period activity represented the saccade direction. These results indicate that task-related MD activity represents either visual or motor information, suggesting that the MD participates in sensory-to-motor information processing. However, a greater proportion of delay- and response-period activities represented the saccade direction in the MD than in the DLPFC, indicating that more MD neurons participate in prospective information processing than DLPFC neurons. These results suggest that although functional interactions between the MD and DLPFC are crucial to cognitive functions such as working memory, there is a difference in how the MD and DLPFC participate in these functions.

Animals↗