Structural characteristics of the mediodorsal nucleus of the cat thalamus

By means of the light and electron microscopy, construction and architectonics of neurons in the cat thalamus medio-dorsal nucleus are described. Differences in the neuronal body dimentions, their form, number of deferent dendrites and character of axonal branching made it possible to define 3 types of neurons. Applying the method based on retrograde axonal transport of exogenous horse-radish peroxidase, it was demonstrated that neurons of type II, contrary to the existing opinion, send their axons into the prefrontal cortex and, hence, are associative-projective. Ultrastructural difference of axonal terminals, differences in the form and size of synaptic vesicles made it possible to reveal 5 types of presynapses.     

GABAergic and cholinergic basal forebrain and preoptic-anterior hypothalamic projections to the mediodorsal nucleus of the thalamus in the cat

The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. The glutamic acid decarboxylase-positive and choline acetyltransferase-positive retrogradely-labelled neurons are distributed throughout several regions of the basal forebrain, including the medial septum, the diagonal band of Broca, the magnocellular preoptic nucleus, the substantia innominata pars anterior, the substantia innominata pars posterior, and the globus pallidus where only a few retrogradely-labelled neurons were seen. The choline acetyltransferase-positive mediodorsal-projecting neurons are morphologically different from the choline acetyltransferase-positive neurons in the basal forebrain, suggesting that those projecting to the mediodorsal nucleus are a small proportion of the cholinergic neuronal population in the basal forebrain. In the preoptic-anterior hypothalamus, many retrogradely-labelled glutamic acid decarboxylase-positive cells were found, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. These retrogradely-labelled glutamic acid decarboxylase-positive neurons are distributed throughout the preoptic-anterior hypothalamus in a continuous line with those in the basal forebrain, including the lateral preoptic area, the medial preoptic area, the bed nucleus of the stria terminalis, and the anterior and dorsal hypothalamic areas. The highest percentage of mediodorsal-projecting GABAergic neurons is in the anterior lateral hypothalamus where more than 25% of the total population of glutamic acid decarboxylase-positive cells project to the mediodorsal nucleus of the thalamus. Overall, of the large population of retrogradely-labelled neurons in the basal forebrain and preoptic-anterior hypothalamus, a significant proportion are glutamic acid decarboxylase-positive neurons (> 60% in the basal forebrain and > 30% in the preoptic-anterior hypothalamus), while the choline acetyltransferase-positive neurons amount to a smaller percentage of the neurons projecting to the mediodorsal nucleus (< 13% in the basal forebrain and < 2% in the preoptic-anterior hypothalamus). These results provide anatomical evidence of direct GABAergic projections from the basal forebrain and preoptic-anterior hypothalamic regions to the "intermediate" part of the mediodorsal nucleus in the cat. This GABAergic projection field could be the direct pathway by which the basal forebrain directly modulates thalamic excitability and may also be involved in mechanisms modulating electroencephalographic synchronization and sleep through the "intermediate" mediodorsal nucleus.     

Visual and vestibular influences on head-direction cells in the anterior thalamus of the rat.

As a rat navigates through space, head-direction cells provide an ongoing signal of its momentary directional heading. This directional signal is thought to be generated, in part, by a dead-reckoning mechanism that uses angular motion information to constantly update the directional representation. This study investigated what kinds of angular motion information might be used for dead reckoning. Anterior thalamic head-direction cells were recorded from rats in a rotatable, cylindrical chamber, which could independently deliver visual motion cues and vestibular cues. Results suggest that both of these angular motion cues have an influence on head-direction cells and may thus be used for dead reckoning. The authors conclude that vestibular and visual movement cues work interactively, along with visual landmarks and motor signals, to determine the directional frame of reference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the mediodorsal nucleus of the thalamus and classical eyeblink conditioning under less-than-optimal stimulus conditions: Role of partial reinforcement and interstimulus interval.

Rabbits received lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions and were subjected to classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 50% or 25% reinforcement with a periorbital shock unconditioned stimulus. Other groups received an interstimulus interval (ISI) of either 1.0 or 1.5 s. Animals with MD lesions acquired the EB conditioned response (CR) more slowly than sham-lesioned animals with either the 1.5-s ISI or with the 25% reinforcement schedule. The lesions had no significant effect on the HR CR, however. Results suggest that information processed by MD is relayed to the prefrontal cortex and is required for somatomotor response selection under nonoptimal learning conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-voltage-activated calcium currents in neurons acutely isolated from the ventrobasal nucleus of the rat thalamus

We studied the high-voltage-activated (HVA) calcium currents in cells isolated from the ventrobasal nucleus of the rat thalamus with the use of the whole cell patch-clamp technique. Low-voltage-activated current was inactivated by the use of long voltage steps or 100-ms prepulses to -20 mV. We used channel blocking agents to characterize the currents that make up the HVA current. The dihydropyridine (DHP) antagonist nimodipine (5 microM) reversibly blocked 33 +/- 1% (mean +/- SE), and omega-conotoxin GVIA (1 microM) irreversibly blocked 25 +/- 5%. The current resistant to DHPs and omega-conotoxin GVIA was inhibited almost completely by omega-conotoxin MVIIC (90 +/- 5% at 3-5 microM) and was partially inhibited by omega-agatoxin IVA (54 +/- 4% block at 1 microM). We conclude that there are at least four main HVA currents in thalamic neurons: N current, L current, and two omega-conotoxin MVIIC-sensitive currents that differ in their sensitivity to omega-agatoxin IVA. We also examined modulation of HVA currents by strong depolarization and by G protein activation. Long (approximately 1 s), strong depolarizations elicited large, slowly deactivating tail currents, which were sensitive to DHP antagonists. With guanosine 5'-0-(3-thiotriphosphate) (GTP-gamma-S) in the intracellular solution, brief (approximately 20 ms), strong depolarization produced a voltage-dependent facilitation of the current (44 +/- 5%), compared with cells with GTP (22 +/- 7%) or guanosine 5'-O-(2-thiodiphosphate) (7 +/- 4%). However, the HVA current was inhibited only weakly by 100 microM acetylcholine (8 +/- 4%). Effects of the gamma-aminobutyric acid-B agonist baclofen were variable (3-39% inhibition, n = 12, at 10-50 microM).     

Directionally selective mnemonic properties of neurons in the lateral dorsal nucleus of the thalamus of rats

The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animal's head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep-layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2-3 min. After this time, the directional preference (but not specificity) appeared to "rotate" systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems.     

Correlation of effects of general anesthetics on somatosensory neurons in the primate thalamus and cortical EEG power

The effects of two types of general anesthetic on the neurophysiological properties of the primate somatosensory thalamus were correlated with effects on frontal cortex electroencephalographic (EEG) power and spectral properties. Graded doses of the intravenous agent methohexital sodium (METH) were studied in 12 cells in three monkeys on a halothane baseline anesthetic. Low doses of METH (0.2-1.0 mg/kg) produced a reduction of EEG power but had no effects on spontaneous or evoked thalamic activity. EEG power showed maximal attenuation after 2.0 mg/kg METH, whereas decreases in thalamic activity were first noted over a similar moderate dose range (2.0-5.0 mg/kg). The physiological parameter most sensitive to METH was the spontaneous activity, which showed initial changes in rate and moderate doses followed by marked inhibition at higher doses. Finally, the high dose of METH (10.0 mg/kg) produced marked reduction in all neurophysiological parameters with recovery over the following 30-45 min. The effects of the volatile anesthetic halothane were studied on 15 cells in four monkeys anesthetized with pentobarbital sodium. The low dose of halothane (0.25%) produced a facilitation of responses to cutaneous stimuli as well as decrease in the rate and burst patterns in the spontaneous activity. The power in the EEG was not affected at this concentration. The responses of the cells to the mechanical stimuli at moderate doses (0.5-1.0%) of halothane returned to the baseline magnitude, whereas spontaneous activity remained unaffected compared with initial effects. EEG power was reduced by 1% halothane. Finally, all neurophysiological parameters showed profound reduction at the highest halothane concentrations (2.0-3.0%) with recovery over the next 30-45 min. In conclusion, the two classes of anesthetics most commonly used for acute neurophysiological studies in the primate show well-defined thresholds at which changes in the response properties of thalamic neurons are produced. This threshold for the barbiturates and halothane can be predicted by monitoring of cortical EEG.     

Response of cat cortical neurons to position and movement of the femur

The contribution of joint afferents to the response of cortical neurons in area 3a to mechanical stimulation of the contralateral hindlimb was evaluated in cats anesthetized with sodium pentobarbital and paralyzed with pancuronium bromide. The hindlimb projection to the pericruciate cortex was established by recording the evoked potentials to electrical stimulation of the sciatic nerve and some of its branches, the bicepssemitendinosus and the quadratus femoris. Out of 169 neurons, 63 responded exclusively to cutaneous stimuli (superficial), whereas the others could be activated by local pressure of hindlimb muscles and/or by joint rotation (deep). Deep neurons were classified as slowly adapting (SA) or rapidly adapting (RA) units. In the neurons responding exclusively to joint rotation, the site of the receptive field could not be identified with certainty. In 13 deep neurons, their firing was affected by rotation of multiple joints of the contralateral hindlimb. In an attempt to identify the source of activation of cortical neurons, partial denervations and muscle disconnections were performed in five animals to isolate and stimulate the hip capsule. In these preparations, in 14 of 15 cortical neurons the source of activation was localized in the periarticular muscles, with no response to mechanical stimulation of the joint capsule. Only one neuron (SA) could be selectively excited by punctate pressure on the hip capsule. Our results suggest that in neurons of area 3a of the cat, the information about the position of the femur relies mainly on muscle afferents.     

Morphologic characteristics of physiologically defined neurons in the cat trigeminal nucleus principalis

Although the principalis nucleus (Vp) contains trigeminothalamic and internuclear tract cells, the functional and morphologic differences between the two kinds of neurons have remained unsettled. The present study was aimed to address these problems by using the intracellular horseradish peroxidase injection technique in the cat. Of 20 neurons stained, 7 and 13 were located in the dorsomedial subnucleus (Vpd) and ventrolateral subnucleus (Vpv) of Vp, respectively. The Vpd neurons received input from the intraoral structures only but the Vpv neurons from the intraoral or facial structures. Nineteen neurons could be divided as class I and class II, based on the branching pattern of their stem axons. Class I (eight neurons) had an ascending stem axon without branching. Class II was divided into two subclasses (IIa and IIb). Class IIa (eight neurons) had an ascending stem axon from which branches were given off. Their branches formed a local-circuit restricted to the lower brainstem. Class IIb (three neurons) had a stem axon that formed the local-circuit only. The dendritic morphology was indistinguishable between different classes of neurons and between the subdivisions. Although the dendritic arborization pattern was governed by the location of the somata, it was suggested to be also important elements for determining primary afferent arborizations. In the brainstem nuclei, the jaw-closing motor nucleus received the highest density of projections from class II neurons with the receptive field involving the periodontal ligaments. The present study provides new findings that Vp neurons could be divided into three distinct populations and suggests that each population exerts a distinct function with respect to sensory discrimination, sensorimotor reflexes, or both.     

Glutamate, gamma-aminobutyric acid and tachykinin-immunoreactive synapses in the cat nucleus tractus solitarii

Neurophysiological and pharmacological evidence suggests that glutamate, gamma-aminobutyric acid and tachykinins (substance P and neurokinin A) each have a role in cardiovascular regulation in the nucleus tractus solitarii. This study describes the ultrastructural relationships between nerve terminals immunoreactive for these substances in the nucleus tractus solitarii of the cat using post-embedding immunogold (single and double) labelling techniques on sections of tissue embedded in LR White resin. The technique combines a high specificity of labelling with good ultrastructural and antigenic preservation. Glutamate-immunoreactive terminals, recognized by their high density of gold particle labelling compared to the mean tissue level of labelling, accounted for about 40% of all synaptic terminals in the region of the nucleus tractus solitarii analysed (medial, dorsal, interstitial, gelatinosus and dorsolateral subnuclei). They appeared to comprise several morphological types, but formed mainly asymmetrical synapses, most often with dendrites of varying size, and contained spherical clear vesicles together with fewer dense-cored vesicles. Substance P- and neurokinin A-immunoreactive terminals were fewer in number (9% of all terminals) but similar in appearance, with the immunoreaction restricted to the dense-cored vesicles. Analysis of serial- and double-labelled sections showed a co-existence of substance P and neurokinin A-immunoreactivity in 21% of glutamate-immunoreactive terminals. Immunoreactivity for gamma-aminobutyric acid was found in 33% of all terminals in the nucleus tractus solitarii. These predominantly contained pleomorphic vesicles and formed symmetrical synapses on dendrites and somata. Possible sites of axo-axonic contact by gamma-aminobutyric acid-immunoreactive terminals onto glutamate-or tachykinin-immunoreactive terminals were rare, but examples of adjacent glutamate and gamma-aminobutyric acid-immunoreactive terminals synapsing on the same dendritic profile were frequent. These results provide an anatomical basis for a gamma-aminobutyric acid mediated inhibition of glutamatergic excitatory inputs to the nucleus tractus solitarii at a post-synaptic level.     

Effects of cortical stimulation on red nucleus neurons in the guinea pig

The aim of the present work was to study the control that the cerebral cortex exerts on red nucleus (RN) neurons in the guinea pig. The experiments were carried out in anaesthetized animals. Electrical stimulation of localized cortical foci was performed by tungsten microelectrodes in frontal and parietal regions containing sensorimotor representations of the body. Single unit RN activity was extracellularly recorded through glass micropipettes, and the encountered RN neurons were recognized by searching their peripheral receptive field. Then, corticorubral influences were tested on RN neurons whose receptive field was located in the same body regions where motor responses were evoked by cortical stimulation. The stimulation with a single pulse evoked complex responses, typically consisting of long lasting inhibitions sometimes preceded by a weak facilitation and always followed by an excitatory rebound. The application of a second pulse modified this pattern, depending on the time interval between the two stimuli. In fact, the reduction of the interval below 300 ms enhanced the excitatory components whereas it shortened the inhibitory component; moreover, an "early" facilitation was evoked but only at intervals as short as 50-150 ms, or less. These results suggest that the corticorubral control may vary according to different levels of cortical activation, becoming more and more facilitatory as the cortical discharges increase from low frequency values (tonic activity) towards high frequency values (phasic activity).     

Preproenkephalin messenger RNA-expressing neurons in the rat parabrachial nucleus: subnuclear organization and projections to the intralaminar thalamus

The pontine parabrachial nucleus, which is a key structure in the central processing of autonomic, nociceptive and gustatory information, is rich in a variety of neuropeptides. In this study we have analysed the distribution of parabrachial neurons that express preproenkephalin messenger RNA, which encodes for the precursor protein for enkephalin opioids. Using an in situ hybridization method, we found that preproenkephalin messenger RNA-expressing neurons were present in large numbers in four major areas of the parabrachial nucleus: the K?lliker-Fuse nucleus, the external lateral subnucleus, the ventral lateral subnucleus, and in and near the internal lateral subnucleus. Many preproenkephalin messenger RNA-expressing neurons were also seen in the central lateral subnucleus, and in the medial and external medial subnuclei. Few labeled neurons were found in the dorsal and superior lateral subnuclei. Injection of the retrograde tracer substance cholera toxin subunit B into the midline and intralaminar thalamus demonstrated that the enkephalinergic neurons in and near the internal lateral subnucleus were thalamic-projecting neurons. Taken together with the results of previous tract-tracing studies, the present findings show that many of the enkephalinergic cell groups in the parabrachial nucleus are located within the terminal zones of the ascending projections that originate from nociresponsive neurons in the medullary dorsal horn and spinal cord, as well as from viscerosensory neurons within the nucleus of the solitary tract. The enkephalinergic neurons in the parabrachial nucleus may thus transmit noci- and visceroceptive-related information to their efferent targets. On the basis of the present and previous observations, we conclude that these targets include the intralaminar and midline thalamus, the ventrolateral medulla and the spinal cord. Through these connections, nociceptive and visceroceptive stimuli may influence several functions, such as arousal, respiration and antinociception.     

Pharmacological characterisation of excitatory synaptic transmission in the cat red nucleus in vivo

Extracellular recordings were made from the magnocellular neurones of the red nucleus (mRN) in anaesthetised cats. A study was made of the effects of selective excitatory amino acid receptor antagonists on excitatory monosynaptic responses evoked from the sensorimotor cortex (SMC) and cerebellar interpositus nucleus (IPN). Iontophoretically applied CNQX and NBQX antagonised both SMC and IPN responses whereas, D-AP5 inhibited the SMC response but was ineffective to the IPN. At currents that selectively antagonised NMDA responses, CPPene had no effect on either SMC or IPN responses. 7-chlorokynurenate inhibited both SMC and IPN responses but required currents that antagonised both AMPA and NMDA responses and was therefore acting in a non-selective manner. Iontophoretically applied glycine was inhibitory to both agonist and synaptic responses, whilst D-serine potentiated NMDA responses but did not enhance monosynaptic responses of the SMC. However in the presence of either 7-chlorokynurenate or high currents of CNQX that reduced the SMC synaptic activation of the mRN neurones, D-serine attenuated the inhibitory action of these antagonists. It is concluded that monosynaptic responses from the SMC are mediated by both NMDA and non-NMDA receptors whereas the monosynaptic responses evoked from the IPN are mediated only by non-NMDA receptors. The lack of effect of CPPene is consistent with the postulate that two NMDA receptor subtypes are present on mRN neurones.     

Response classes in the dorsal cochlear nucleus and its output tract in the chloralose-anesthetized cat

Neurons in the dorsal cochlear nucleus (DCN) can be classified into three major physiological classes on the basis of responses to pure tone and broadband noise stimuli. A circuit diagram that associates these classes with different cell types has been proposed. According to this proposal, type II cells are inhibitory interneurons that respond well to tones and poorly to broadband noise, type IV cells are projection neurons with the opposite behavior, and type III cells are an inhomogeneous class with intermediate properties. To test the associations proposed, I compared the response type distribution in the DCN with its output tract, the dorsal acoustic stria (DAS), in chloralose-anesthetized cats. Axonal recordings in the DAS showed type III and IV responses as in DCN, but no type II responses. Compared with reports in decerebrate animals, fewer type IV neurons were encountered having sustained inhibition that generated strongly nonmonotonic responses to tones in both DCN and DAS. The presence of type II responses in the nucleus, but not in the output tract, offers strong support for the proposed association with DCN interneurons. On the other hand, the distinction between type III and IV responses needs refinement because the differences are only graded and because both types of responses occur in DAS, which shows that they are both associated with projection neurons.     

Effects of saccades on the activity of neurons in the cat lateral geniculate nucleus

Effects of saccades on individual neurons in the cat lateral geniculate nucleus (LGN) were examined under two conditions: during spontaneous saccades in the dark and during stimulation by large, uniform flashes delivered at various times during and after rewarded saccades made to small visual targets. In the dark condition, a suppression of activity began 200-300 ms before saccade start, peaked approximately 100 ms before saccade start, and smoothly reversed to a facilitation of activity by saccade end. The facilitation peaked 70-130 ms after saccade end and decayed during the next several hundred milliseconds. The latency of the facilitation was related inversely to saccade velocity, reaching a minimum for saccades with peak velocity >70-80 degrees /s. Effects of saccades on visually evoked activity were remarkably similar: a facilitation began at saccade end and peaked 50-100 ms later. When matched for saccade velocity, the time courses and magnitudes of postsaccadic facilitation for activity in the dark and during visual stimulation were identical. The presaccadic suppression observed in the dark condition was similar for X and Y cells, whereas the postsaccadic facilitation was substantially stronger for X cells, both in the dark and for visually evoked responses. This saccade-related regulation of geniculate transmission appears to be independent of the conditions under which the saccade is evoked or the state of retinal input to the LGN. The change in activity from presaccadic suppression to postsaccadic facilitation amounted to an increase in gain of geniculate transmission of approximately 30%. This may promote rapid central registration of visual inputs by increasing the temporal contrast between activity evoked by an image near the end of a fixation and that evoked by the image immediately after a saccade.