Cholinergic responses of morphologically and electrophysiologically characterized neurons of the basolateral complex in rat amygdala slices

The electrophysiological properties, the response to cholinergic agonists and the morphological characteristics of neurons of the basolateral complex were investigated in rat amygdala slices. We have defined three types of cells according to the morphological characteristics and the response to depolarizing pulses. Sixty-six of the recorded cells (71%) responded with two to three action potentials, the second onwards having less amplitude and longer duration (burst). In a second group, consisting of 21 cells (22%), the response to depolarization was a train of spikes, all with the same amplitude (multiple spike). Finally, seven neurons (7%) showed a single action potential (single spike). Burst response and multiple-spike neurons respond to the cholinergic agonist carbachol (10-20 microM) with a depolarization that usually attained the level of firing. This effect was accompanied by decreased or unchanged input membrane resistance and was blocked by atropine (1.5 microM). The depolarizing response to superfusion with carbachol occurred even when synaptic transmission was blocked by tetrodotoxin, indicating a direct effect of carbachol. Similarly, the depolarization by carbachol was still present when the M-type conductance was blocked by 2 mM Ba2+. The carbachol-induced depolarization was prevented by superfusion with tetraethylammonium (5 mM). Injection of biocytin into some of the recorded cells and subsequent morphological reconstruction showed that "burst" cells have piriform or oval cell bodies with four or five main dendritic trunks; spines are sparse or absent on primary dendrites but abundant on secondary and tertiary dendrites. This cellular type corresponds to a pyramidal morphology. The "multiple-spike" neurons have oval or fusiform somata with four or five thick primary dendritic trunks that leave the soma in opposite directions; they have spiny secondary and tertiary dendrites. Finally, neurons which discharge with a "single spike" to depolarizing pulses are round with four or five densely spiny dendrites, affording these neurons a mossy appearance. The results indicate that most of the amygdaloid neurons respond to carbachol with a depolarization. This effect was concomitant with either decrease or no change in the membrane input resistance and was not blocked by the addition of Ba2+, an M-current blocker, indicating that a conductance pathway other than K+ is involved in the response to carbachol.     

Light- and electron-microscopic study of electrophysiologically characterized neurons in the mediolateral part of the lateral spetum of the guinea-pig

In slices of guinea-pig brains, 36 neurons located in the mediolateral part of the lateral septum were stained intracellularly with horseradish peroxidase (n = 28) or biocytin (n = 8) after electrophysiological characterization. These neurons belonged to class A neurons (n = 23), which generated pronounced Ca(++)-dependent high-threshold spikes in control medium, or to class C neurons (n = 9), which were recognized by the occurrence of small-amplitude sodic spikes followed by slower larger calcic spikes. The present results demonstrate that, despite the variety of individual cell types, the major morphological population (30/36 cells) was composed of a homogeneous class of large-sized neurons that displayed thick primary dendrites and abundant dendritic appendages. The remaining 6 cells were small-sized, poorly-spiny neurons. Somatic spines were observed on 5 out of the 30 large cells and on one out of the six smaller cells. Labeled axons were mainly oriented to the anterior commissure. The axons of nine cells richly collateralized near the perikaryon. Ultrastructural examination of 3 horseradish peroxidase-injected cells showed indented nuclei, classic organelles and somatic spines. Terminal boutons established symmetric synapses with the injected cells. These results describe the morphological features of electrophysiologically identified neurons and indicate that class A and class C neurons are distributed among morphological populations differing in perikaryal size. This suggests that the different electrical properties of class A and class C neurons reflect recordings from different parts of the neuron rather than from neurons of different types. Furthermore, the present findings demonstrate that, in the guinea-pig, electrical and morphological characteristics of somatospiny neurons are comparable with those of non-somatospiny neurons. Somatospiny neurons have a recognized integrative role in the hippocampo-septo-hypothalamic complex.     

Fos and serotonin immunoreactivity in the raphe nuclei of the cat during carbachol-induced active sleep: a double-labeling study

The microinjection of carbachol into the nucleus pontis oralis produces a state which is polygraphically and behaviorally similar to active sleep (rapid eye movement sleep). In the present study, using double-labeling techniques for serotonin and the protein product of c-fos (Fos), we sought to examine whether immunocytochemically identified serotonergic neurons of the raphe nuclei of the cat were activated, as indicated by their expression of c-fos, during this pharmacologically-induced behavioral state (active sleep-carbachol). Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited a significantly greater number of c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus. Whereas most of the c-fos-expressing neurons in the raphe dorsalis were small, those in the raphe magnus were medium-sized and in the raphe pallidus they were small and medium-sized. The mean number of serotonergic neurons that expressed c-fos (i.e. double-labeled cells) was similar in control and active sleep-carbachol cats. These data indicate that there is an increased number of non-serotonergic, c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus during the carbachol-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Projections from the presubiculum and the parasubiculum to morphologically characterized entorhinal-hippocampal projection neurons in the rat

The relations between the inputs from the presubiculum and the parasubiculum and the cells in the entorhinal cortex that give rise to the perforant pathway have been studied in the rat at the light microscopical level. Projections from the presubiculum and the parasubiculum were labeled anterogradely, and, in the same animal, cells in the entorhinal cortex that project to the hippocampal formation were labeled by retrograde tracing and subsequent intracellular filling with Lucifer Yellow. The distribution and the number of appositions between the afferent fibers and hippocampal-projection neurons in the various layers of the entorhinal cortex were analyzed. The results show that layers I-IV of the entorhinal cortex contain neurons that give rise to projections to the hippocampal formation. The morphology of these projection neurons is highly variable and afferents from the presubiculum and the parasubiculum do not show a preference for any specific morphological cell type. Both inputs preferentially innervate the dendrites of their target cells. However, presubicular and parasubicular projections differ with respect to the layer of entorhinal cortex they project to. The number of appositions of presubicular afferents with cells that have their cell bodies in layer III of the entorhinal cortex is 2-3 times higher than with cells in layer II. In contrast, afferents from the parasubiculum form at least 2-3 times as many synapses on the dendrites of cells located in layer II than on neurons that have their cell bodies in layer III. Cells in layers I and IV of the entorhinal cortex receive weak inputs from the presubiculum and parasubiculum. Not only is the presubiculum different from the parasubiculum with respect to the distribution of projections to the entorhinal cortex, they also differ in their afferent and efferent connections. In turn, cells in layer II of the entorhinal cortex differ in their electrophysiological characteristics from those in layer III. Moreover, layer II neurons give rise to the projections to the dentate gyrus and field CA3/CA2 of the hippocampus proper, and cells in layer III project to field CA1 and the subiculum. Therefore, we propose that the interactions of the entorhinal-hippocampal network with the presubiculum are different from those with the parasubiculum.     

NADPH-diaphorase-positive neurons and pathways in the brain of the frog Rana esculenta

We described the NADPH-diaphorase-containing neurons and fibres in the brain of the frog Rana esculenta. In the telencephalon stained cells occurred in the olfactory bulb, all subdivisions of the pallium, the diagonal band, the medial septum and the striatum. The olfactory glomeruli showed the most intense enzyme reaction. The neuropil of the accessory olfactory bulb was also heavily stained and this staining extended to the rostral diencephalon through the ventral lateral pallium. Fibre staining was less intense in the medial pallium and the medial septum. In the diencephalon, NADPH-diaphorase staining was concentrated in the middle third of this part of the brain. The stained cells were embedded in a dense network of thin, stained fibres and terminals in the lateral anterior and central thalamic nuclei. Faintly stained cells were present also in the posterior preoptic nucleus, anterior thalamic nucleus, nucleus of Bellonci, corpus geniculatum thalamicum and the suprachismatic nucleus. In the mesencephalon, heavily stained cells occurred in the nucleus profundus mesencephali, anterodorsal, anteroventral and especially in the posterodorsal tegmental nuclei. Neuronal staining was less intense in the optic tectum and the torus semicircularis. Thick, intensely stained fibres occupied the lateral part of the tegmentum and the 7th layer of the tectum. A loose network of thin fibres occupied the periventricular area and all tegmental nuclei. In the rhombencephalon, the reticular nuclei and the inferior raphe nucleus showed the most intense staining, while some cells in the nucleus of the solitary tract and the dorsal column nuclei were less intensely stained. Heavy staining of fibres was characteristic of the spinal trigeminal tract, the solitary tract and the reticulospinal pathway.     

Localization of preganglionic neurons of the accessory ciliary ganglion in the midbrain: HRP and WGA-HRP studies in the cat

Localization of preganglionic neurons of the accessory ciliary ganglion (ACG), including ectopic intraocular ganglion cells, was investigated in the cat with the aid of horseradish peroxidase (HRP) and HRP-conjugated wheat germ agglutinin (WGA-HRP) methods. When HRP or WGA-HRP was injected into the anterior and posterior chambers of the eye, no retrogradely labeled cells were found in the visceral oculomotor nuclei, although most neurons of the ACG and the main ciliary ganglion (CG) were intensely labeled. When a microsyringe needle was inserted into the ciliary body, the tracer diffused into the suprachoroid lamina and the intraocular ganglion cells, and a small number of labeled neurons appeared in the midplane between each side of the somatic oculomotor nuclei. After injection into the ACG, many labeled neurons were observed in the anteromedian nucleus, Edinger-Westphal nucleus, and midplane between the somatic oculomotor nuclei, their ventral continuations of the ventral tegmental area, and the periaqueductal gray. HRP/WGA-HRP injection into the CG labeled cells in all these areas and in the lateral border zones of the anteromedian, Edinger-Westphal and somatic oculomotor nuclei, and their ventral continuations of the ventral tegmental area. These findings indicate that the visceral oculomotor neurons which project to the ACG tend to be located more medially than those to the CG.     

Morphology and laminar distribution of nonpyramidal neurons in the auditory cortex of the rabbit

A study of the morphology and laminar distribution of nonpyramidal neurons in Golgi-Nissl preparations of electrophysiologically verified auditory cortex was carried out in the adult rabbit. Nonpyramidal neurons were located primarily within laminae I-IV and were only infrequently seen in lamina V and VI. In lamina I, four nonpyramidal cell types were observed: (1) small, spine-free horizontal neurons, (2) small, sparsely spined multipolar neurons with radiate dendrites, (3) large, multipolar neurons with fusiform somata and vertically aligned, sparsely spined dendrites, and (4) small, spine-free neurogliform neurons. The horizontal and small multipolar neurons had tangentially running axons confined to lamina I. The large, fusiform cells had descending axons which arborized in lamina II and occasionally reached lamina III. In lamina II and the upper part of lamina III, seven nonpyramidal cell types were observed: (1) spine-free bipolar neurons with vertically aligned dendrites and axonal arbors; (2) large, (3) medium, and (4) small, spine-free and sparsely spined multipolar neurons, all with locally ramifying axons; (5) pear-shaped cells with highly oriented dendrites which branched toward the pial surface and vertically arborizing axons; (6) multipolar cells with tangentially and vertically oriented dendrites and ascending axons which entered lamina I, and (7) tufted cells with local axons. Three types of nonpyramidal cells were observed in lamina IV and the lower part of lamina III: (1) large, multipolar cells with radiate, spine-free dendrites and stout axons which arborized locally, (2) spiny multipolar cells with vertically aligned dendrites and ascending axons which arborized in lamina II and III via long horizontal collaterals, and (3) spine-free bipolar cells with vertical dendrites and axons which arborized in a narrow vertical column adjacent to the dendrites. Nonpyramidal neurons in lamina V and VI were primarily multipolar cells with sparsely spined and spine-free dendrites. A comparison of these data with those of other species indicates that the neuronal organization of the rabbit auditory cortex is similar to that of the sensory cortex of the rodent but is strikingly different from that of carnivores and primates.     

Direct parabrachial nuclear projections to the pharyngeal motoneurons in the rat: an anterograde and retrograde double-labeling study

The parabrachial nucleus consists of several subnuclei which contains autonomic, gustatory, visceral sensory, nociceptive, and respiratory related neurons. We have investigated the direct projections from the rat parabrachial region, including the K olliker-Fuse nucleus, to the pharyngeal motoneurons with an anterograde and retrograde double-tracing technique. The cholera toxin subunit-B was injected into the lower pharynx or the esophagus after injection of biotinylated dextran amine into the ventrolateral parabrachial nuclear region, including the external medial, the external lateral, and the crescent area of the central lateral parabrachial nuclei and into the K?lliker-Fuse nucleus. The anterogradely dextran amine-labeled fibers from these nuclei projected to the semicompact, loose and external formations besides the compact formation of the nucleus ambiguus. Many anterogradely labeled fibers and terminals were found to contact retrogradely cholera toxin-labeled pharyngeal neuronal soma and dendrites in the semicompact formation of the nucleus ambiguus. The medial half of the parabrachial nucleus, including the medial and the medial part of the central lateral parabrachial nuclei, sent a few fibers to the reticular formation just dorsal to the esophageal motoneurons but no fibers to either the pharyngeal or to the esophageal motoneurons. These results suggested that the visceral sensory, gustatory, nociceptive or respiratory related neurons in the parabrachial nucleus project directly to the pharyngeal motoneurons, but there are no parabrachial projections to the esophageal motoneurons in the nucleus ambiguus.     

Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons

Neurturin (NTN) is a neurotrophic factor that shares homology with glial cell line-derived neurotrophic factor (GDNF). Recently, a receptor complex has been identified for GDNF that includes the Ret tyrosine kinase receptor and a glycosylphosphatidylinositol-linked protein termed "GDNFRalpha." However, differences in the phenotype of Ret and GDNF knockout animals suggest that Ret has at least one additional ligand. In this report, we demonstrate that NTN induces Ret phosphorylation in primary cultures of rat superior cervical ganglion (SCG) neurons. NTN also caused Ret phosphorylation in fibroblasts that were transfected stably with Ret and GDNFRalpha but not in cells expressing Ret alone. A glycosylphosphatidylinositol-linked protein also was important for NTN and GDNF signaling in SCG neurons; phosphatidylinositol-specific phospholipase C treatment of SCG cultures reduced the ability of NTN to phosphorylate Ret and the ability of NTN or GDNF to activate the mitogen-activated protein kinase pathway. NTN and GDNF also caused sustained activation of Ret and the mitogen-activated protein kinase pathway in SCG neurons. Finally, both NTN and GDNF activated the phosphatidylinositol 3-kinase pathway in SCG neurons, which may be important for the ability of NTN and GDNF to promote neuronal survival. These data indicate that NTN is a physiologically relevant ligand for the Ret receptor and suggest that NTN may have a critical role in the development of many neuronal populations.     

Interrelationship between differently spaced neurons in the auditory and motor zones of the cerebral cortex in cats

Multineuronal activity was studied in unrestrained cats with bundles of seven electrodes (tips dia. 50 mcm) chronically implanted in the auditory and motor cortex. Spikes of the highest and lowest amplitude were isolated from each neurogram by an amplitude discriminator. Functional connections between neurones located under different electrodes at a distance of up 540 mcm were defined by statistical dependence of the isolated spike series. In the auditory cortex, the distance at which it was possible to detect connections between high amplitude neurones (H-H) did not exceed 450 mcm, while between low amplitude neurones (L-L) it was 270 mcm. In the motor cortex, dependent relations for similar pairs of neurones (H-H) and (L-L) were found at all the studied distances up to 540 mcm. For mixed neuronal pairs (H-L and L-H) functional connections at different distances were differently expressed at various distances.     

Temporal and spectral sensitivity of complex auditory neurons in the nucleus HVc of male zebra finches

Complex vocalizations, such as human speech and birdsong, are characterized by their elaborate spectral and temporal structure. Because auditory neurons of the zebra finch forebrain nucleus HVc respond extremely selectively to a particular complex sound, the bird's own song (BOS), we analyzed the spectral and temporal requirements of these neurons by measuring their responses to systematically degraded versions of the BOS. These synthetic songs were based exclusively on the set of amplitude envelopes obtained from a decomposition of the original sound into frequency bands and preserved the acoustical structure present in the original song with varying degrees of spectral versus temporal resolution, which depended on the width of the frequency bands. Although both excessive temporal or spectral degradation eliminated responses, HVc neurons responded well to degraded synthetic songs with time-frequency resolutions of approximately 5 msec or 200 Hz. By comparing this neuronal time-frequency tuning with the time-frequency scales that best represented the acoustical structure in zebra finch song, we concluded that HVc neurons are more sensitive to temporal than to spectral cues. Furthermore, neuronal responses to synthetic songs were indistinguishable from those to the original BOS only when the amplitude envelopes of these songs were represented with 98% accuracy. That level of precision was equivalent to preserving the relative time-varying phase across frequency bands with resolutions finer than 2 msec. Spectral and temporal information are well known to be extracted by the peripheral auditory system, but this study demonstrates how precisely these cues must be preserved for the full response of high-level auditory neurons sensitive to learned vocalizations.     

Activity and excitability to electrical current of cortical auditory receptive neurons of awake cats as affected by stimulus association

1. Unit activity and excitability were studied at the midlateral and suprasylvian cortex of naive, blink-conditioned and "randomization" cats. The latter received the same CS and US as did the conditioned animals, but in random temporal order and with random intertrial intervals with mean comparable to that used for conditioning. The randomization group failed to develop a blink CR. 2. With conditioning, spontaneous and evoked unit discharges were increased above levels found in naive animals. Correspondingly, levels of extracellularly injected current required to elicit a spike discharge were lower in conditioned than in naive animals. In addition, in the conditioned animals, the degree of enhancement of evoked activity and excitability was found to be greatest in the units that responded to the CS, as opposed to units that responded to another auditory stimulus of equal intensity but of no special behavioral significance vis-a-vis the conditioned reflex. 3...     

Distinct activation of monoaminergic pathways in chick brain in relation to auditory imprinting and stressful situations: a microdialysis study

In the forebrain of the domestic chick (Gallus gallus domesticus), an area termed the mediorostral neostriatum/hyperstriatum ventrale is strongly involved in emotional learning paradigms such as acoustic filial imprinting. Furthermore, the involvement of the mediorostral neostriatum/hyperstriatum ventrale in stressful situations, such as social separation, has been demonstrated in 2-deoxyglucose studies. The aim of the present study was to examine whether quantitative changes of dopamine, serotonin and their metabolites occur during auditory filial imprinting and during social separation. Using in vivo microdialysis in tone-imprinted and in naive, control chicks, we compared the extracellular levels of homovanillic acid, a metabolite of dopamine, and 5-hydroxyindoleacetic acid, a metabolite of serotonin, during the presentation of the imprinting tone. A small, but statistically significant, decrease of extracellular homovanillic acid levels was found in the mediorostral neostriatum/hyperstriatum ventrale of imprinted chicks compared to control animals, whereas changes of 5-hydroxyindoleacetic acid were not detected. In a second experiment, we investigated the levels of homovanillic acid and 5-hydroxyindoleacetic acid in the mediorostral neostriatum/hyperstriatum ventrale of socially reared chicks during different stress situations, such as handling or separation from their cage mates. Handling induced a significant increase of homovanillic acid and 5-hydroxyindoleacetic acid, while social separation resulted in a significant increase of 5-hydroxyindoleacetic acid and only a slight increase of homovanillic acid. Despite considerable inter-individual variability, the increase of distress vocalizations (duration of distress calls) after social separation displayed a good correlation to the increased 5-hydroxyindoleacetic acid levels in all animals analysed. These results provide the first evidence that the physiological response of the mediorostral neostriatum/hyperstriatum ventrale related to different emotional conditions after acoustic imprinting and during stressful situations is, at least in part, mediated by dopaminergic and/or serotonergic pathways. Furthermore, the results from the present study indicate a distinct activation of dopaminergic and serotonergic pathways in relation to the behavioural situation and the associated changes of emotional status.     

Topographic bulbar projections and dual neural pathways of the primary olfactory neurons in salmonid fishes

A growing body of evidence indicates spatial patterning of molecular expression and physiological activities in the olfactory epithelium and primary afferent circuits of the vertebrate olfactory bulb. Because our previous studies indicate that olfactory receptors specific for amino acids and a bile acid, taurocholic acid, project to segregated coding centres in the olfactory bulb, we further examined the afferent projections and pathways of the primary neuronal responses to putative pheromones by recording the electroencephalogram from various regions of the olfactory bulb. First, using the electro-olfactogram, we determined olfactory sensitivities of six salmonid species to these odorants. Prostaglandin F2 alpha and 15-keto-prostaglandin F2 alpha were potent olfactory stimulants for all tested salmonids, except rainbow trout (Oncorhynchus mykiss). None of the salmonids responded to 17 alpha,20 beta-dihydroxy-4-pregnen-3-one. However, they were sensitive to etiocholan-3 alpha-ol-17-one glucuronide. In all salmonids examined, electroencephalograms to amino acids and taurocholic acid, applied singly or in combination, projected to two segregated regions, the lateroposterior and mid-olfactory bulb, respectively. Neither prostaglandin F2 alpha, 15-keto-prostaglandin F2 alpha nor etiocholan-3 alpha-ol-17-one glucuronide elicited electroencephalograms. These data indicate that, in salmonids, olfactory neurons responsive to amino acids and taurocholic acid project to spatially segregated regions, and thereby generated signals are encoded spatially and temporarily. The results also suggest that olfactory signals due to hormonal pheromones are processed in a manner distinct from those for amino acids and bile acids, and may possibly be mediated by extrabulbar primary olfactory fibres bypassing the bulb.     

Dissociation of conditioned locomotion and Fos induction in response to stimuli formerly paired with cocaine.

A discrete stimulus (flashing light) was paired with cocaine (20 mg/kg) to induce conditioned locomotion. To identify brain regions activated during this response, Fos was measured with immunohistochemistry. Although paired subjects displayed robust conditioned locomotion, Fos was not increased in any limbic brain regions analyzed. In contrast, pairing of cocaine with generalized contextual cues (whole room) produced conditioned locomotion and Fos activation in the prelimbic portion of prefrontal cortex and the nucleus accumbens core. These results suggest that the pattern of neuronal activation during cocaine-conditioned activity differs depending on whether a discrete or contextual stimulus is used as a conditioned stimulus. The possibility that expectancy and frustrative nonreward contribute to Fos expression in rats conditioned to contextual cues is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial receptive fields of primary auditory cortical neurons in quiet and in the presence of continuous background noise

Spatial receptive fields of primary auditory (AI) neurons were studied by delivering, binaurally, synthesized virtual-space signals via earphones to cats under barbiturate anesthesia. Signals were broadband or narrowband transients presented in quiet anechoic space or in acoustic space filled with uncorrelated continuous broadband noise. In the absence of background noise, AI virtual space receptive fields (VSRFs) are typically large, representing a quadrant or more of acoustic space. Within the receptive field, onset latency and firing strength form functional gradients. We hypothesized earlier that functional gradients in the receptive field provide information about sound-source direction. Previous studies indicated that spatial gradients could remain relatively constant across changes in signal intensity. In the current experiments we tested the hypothesis that directional sensitivity to a transient signal, as reflected in the gradient structure of VSRFs of AI neurons, is also retained in the presence of a continuous background noise. When background noise was introduced three major affects on VSRFs were observed. 1) The size of the VSRF was reduced, accompanied by a reduction of firing strength and lengthening of response latency for signals at an acoustic axis and on-lines of constant azimuth and elevation passing through the acoustic axis. These effects were monotonically related to the intensity of the background noise over a noise intensity range of approximately 30 dB. 2) The noise intensity-dependent changes in VSRFs were mirrored by the changes that occurred when the signal intensity was changed in signal-alone conditions. Thus adding background noise was equivalent to a shift in the threshold of a directional signal, and this shift was seen across the spatial receptive field. 3) The spatial gradients of response strength and latency remained evident over the range of background noise intensity that reduced spike count and lengthened onset latency. Those gradients along the azimuth that spanned the frontal midline tended to remain constant in slope and position in the face of increasing intensity of background noise. These findings are consistent with our hypothesis that, under background noise conditions, information that underlies directional acuity and accuracy is retained within the spatial receptive fields of an ensemble of AI neurons.     

Electrophysiological and Fos immunohistochemical evidence for the excitatory nature of the parafascicular projection to the globus pallidus

Extracellular recordings and immunohistological detection of c-Fos-like immunoreactive proteins were used to determine the synaptic effect of the parafascicular projection to the globus pallidus. Electrical stimulation of the parafascicular neurons induced a single-spike excitatory response with a stable latency of 2.3 ms, suggesting a monosynaptically driven effect. Pharmacological stimulation of the parafascicular nucleus with carbachol increased tonically the pallidal discharge rate by 142%. The discharge rate of the pallidal neurons was described by 37% in parafascicular-lesioned rats. These results demonstrate the excitatory nature and the tonic action of the parafasciculopallidal projection. Carbachol activation of parafascicular neurons also induced the synthesis of c-Fos-like immunoreactive proteins in the pallidal neurons. Control experiments in subthalamic-lesioned rats showed that the parafascicular excitation of the pallidal neurons remained, but both electrophysiological and expression of c-Fos-like immunoreactive proteins were attenuated. This suggests that the direct parafascicular excitation of the pallidal neurons is indirectly reinforced by the previously described parafascicular excitatory input to the subthalamic nucleus. Conversely, the effect of this last input to the subthalamic nucleus is dramatically enhanced in rats with pallidal lesion. Our results demonstrate the complex role of the parafascicular nucleus in activating both the globus pallidus and the subthalamic nucleus, two closely related structures. These results illustrate the integrative capacities of the globus pallidus, whose activity is modulated by multiple afferents.