The nucleus accumbens 5-HTR4-CART pathway ties anorexia to hyperactivity.

In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.

Biochemical and histological changes in the brain of the cricket Nemobius sylvestris infected by the manipulative parasite Paragordius tricuspidatus (Nematomorpha).

Hairworms (nematomorpha) alter the behaviour of their insect hosts, making them commit 'suicide' by jumping into an aquatic environment required by the adult parasite for the continuation of its life cycle. To explore the physiological and neuronal basis of this behavioural manipulation, we first performed a biochemical study to quantify different neurotransmitters or neuromodulators (monoamines and amino acids) in the brain of crickets (Nemobius sylvestris) uninfected and infected by the hairworm Paragordius tricuspidatus. We also analysed several polyamines and amino-acids having no known neuromodulatory function. The presence/absence of the parasite explained the largest part of the variation in compound concentrations, with infected individuals displaying on average lower concentrations than uninfected individuals. However, for three amino acids (taurine, valine and tyrosine), a significant part of the variation was also correlated with the manipulative process. In order to compare neurogenesis between infected and uninfected crickets, we also performed a histological study on mushroom bodies in the cricket's brain. The mitotic index exhibited a two-fold increase in infected crickets as compared with uninfected crickets. This is the first study to document changes in the brain of insects infected by nematomorphs.

Serotonin depletion produces long lasting increase in striatal glutamatergic transmission.

The ability of serotonin (5-HT) to influence striatal glutamatergic transmission was examined by determining changes over time in glutamate extracellular levels, transporter expression and synaptosomal uptake in rats with lesion of serotonergic neurones. By 8 days after intraraphe injections of 5,7-dihydroxytryptamine, producing 80% decreases in striatal tissue 5-HT levels, no changes were observed in the glutamatergic transmission. When 5-HT depletion was almost complete (21 days post-lesion), high affinity glutamate uptake in striatal synaptosomal preparations was significantly increased (156% of control), although no changes in striatal GLT1, GLAST and EAAC1 mRNAs, and GLT1 protein were detected by in situ hybridization and immunohistochemistry. Meanwhile, the serotonin lesion produced large increases in basal extracellular levels of glutamate and glutamine (364% and 259%, respectively) determined in awake rats by in vivo microdialysis, whereas no change was observed in dopamine levels as compared with control rats. High potassium depolarization as well as L-trans-pyrrolidine-2,4-dicarboxylate, also induced larger increases in extracellular levels of glutamate in lesioned rats than in controls. Finally, similar changes in glutamate transmission were observed by 3 months post-lesion. These results suggest that 5-HT has a long lasting and tonic inhibitory influence on the striatal glutamatergic input, without affecting the basal dopaminergic transmission.

Opposite changes in striatal neuropeptide Y immunoreactivity after partial and complete serotonergic depletion in the rat.

The aim of this study was to investigate the consequences of partial vs. complete serotonergic (5-HT) depletions on the immunoreactivity of striatal interneurons containing neuropeptide Y (NPY). Taking into account the plasticity of the monoaminergic neurons, the effects of various doses of 5,7-dihydroxytryptamine (5,7-DHT) injected into the anterior raphe nuclei and P-chlorophenylalanine (PCPA) administration were compared in the dorsal (caudate-putamen) and the ventral (nucleus accumbens) striatum. Twenty days after administering 5,7-DHT injections inducing a substantial but partial decrease in the striatal 5-HT concentrations (about 80%), we detected a significant decrease in the number of NPY immunoreactive cells. In contrast, the PCPA inhibition of serotonin synthesis in the neurons spared by the partial lesion or the near-complete neurotoxic lesion induced an increase in the number of striatal NPY neurons. These results suggest that complex adaptive mechanisms are probably responsible for the changes in striatal NPY reactivity observed after a partial lesion and that these neurons can adapt according to the extent of 5-HT depletion. Upon comparing the NPY responses in the dorsal and ventral components of the striatal complex, no main differences were observed; while in the caudate-putamen, the changes were primarily found to occur in the medial zone. This finding is discussed here with reference to the topographical effects of dopaminergic or glutamatergic deafferentation. Finally, these results suggest that a complete interruption of the 5-HT transmission may lead to an increase in the intracellular NPY level, which may be associated with a decrease in the release of the peptide. It can therefore be postulated that serotonergic neurons normally exert a positive influence on NPY striatal neurons.

Effects of ionotropic excitatory amino acid receptor antagonists on glutamate transport and transport-mediated changes in extracellular excitatory amino acids in the rat striatum.

This study examined the effects of intrastriatal administration of ionotropic excitatory amino acid receptor antagonists on biochemical markers of excitatory amino acid transmission in the rat striatum. High-affinity glutamate uptake was measured ex vivo on striatal homogenates 15 min after the local administration of either 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA receptor antagonist, or DL-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA antagonist, at various doses (10-500 pmol injected). DNQX induced a dose-dependent increase in glutamate uptake rate, related to an increase in the Vmax of the transport process, whereas no significant change in glutamate uptake was detected after AP5 administration. Similar results were obtained from animals subjected to excitotoxic lesion of striatal neurons by kainate administration 15 days before the injection of DNQX or AP5. In a parallel series of experiments using in vivo microdialysis we showed that DNQX (10(-5) M) in the dialysis probe diminished by approximately 30-40% the increases in the concentrations of glutamate and aspartate elicited by L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM). These data suggest that presynaptic glutamate transmission in the rat striatum may undergo facilitatory autoregulatory processes involving ionotropic non-NMDA receptors and highlight the view that transporters for glutamate may be potent regulatory sites for glutamatergic transmission.

Local injections of excitatory amino acid agonists alter the glutamatergic and dopaminergic transmissions in the rat striatum.

This study examined the effects of kainic, ibotenic, and quisqualic acid-induced lesions of the rat striatum on biochemical markers of the glutamatergic corticostriatal and dopaminergic nigrostriatal afferent transmissions. Fifteen to 21 days after striatal injections of these various compounds, significant reductions in the high-affinity glutamate uptake rate, due to decreases in the Vmax of the transport process, were measured. Interestingly, the relationship between these decreases in the Vmax and the decreases in the levels of biochemical markers for the intrinsic striatal cholinergic and GABAergic neurons differed depending on the excitotoxin used. These findings suggest that excitatory amino acid agonists-induced alterations of the glutamatergic terminal activity may not depend only on the loss of cholinergic and GABAergic striatal neurons. In contrast, the observed changes in the dopamine and metabolite contents seemed to be related to the extent of the striatal neuronal degeneration induced by each excitotoxin. All in all, these results indicate that excitatory amino acid agonists can impair the activity and/or the integrity of the two main striatal afferent pathways, through presumably different mechanisms.

Intracerebroventricular administration of neuropeptide Y affects parameters of dopamine, glutamate and GABA activities in the rat striatum.

The effects of intracerebroventricular (ICV) injection of neuropeptide Y (NPY) on parameters of dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) activities were investigated in the rat striatum. NPY (1.17-4.70 nmol) induced a dose-dependent increase in the striatal endogenous DA release monitored in freely moving animals by means of a voltammetric method. Maximal increase was observed about one hour after the peptide injection. This result is consistent with the hypothesis that NPY may influence striatal DA turnover in a facilitatory manner by activating DA release. DA, DOPAC, Glu and GABA endogenous contents as well as 3H-Glu and 3H-GABA synaptosomal high affinity uptakes were examined one hour after NPY ICV administration at the same dose range in chloral hydrate-anesthetized animals. Depending on the NPY dose injected, opposite changes in Glu uptake were observed, suggesting that NPY has a bimodal influence on glutamatergic transmission. The Glu uptake rate increased markedly at 1.17 nmol NPY and decreased at 4.70 nmol, which may reflect an activation and an inhibition of the striatal Glu transmission, respectively. In parallel, the GABA uptake was found to decrease slightly at the higher doses of NPY tested, whereas no significant alteration of the striatal concentrations of either DA, DOPAC, Glu or GABA was observed. These results indicate that NPY may be involved in regulating the activity of nigral dopaminergic and cortical glutamatergic afferent pathways and that of intrinsic GABA neurons in the rat striatum.

Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal neurochemical markers in the rat, with special reference to the dopamine, choline, GABA and glutamate synaptosomal high affinity uptake systems.

Riluzole, a new compound with anticonvulsant properties, was found to induce a dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate into striatal synaptosomes when added to the incubation medium or after in vivo administration, whereas an inhibition of 3H-choline uptake was detected only in the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H-glutamate uptake differentially since 3H-dopamine uptake was found to be more sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake competitively and 3H-glutamate uptake non-competitively, which further suggests that the action of the compound is selective. After in vivo injection, riluzole did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate, aspartate or GABA contents. Since this compound was previously reported to induce a decrease in the spontaneous release of glutamate, serotonin, dopamine and possibly acetylcholine, the hypothesis is put forward that riluzole may, at least at high concentrations, have general effects on the striatal nerve terminals affecting both the uptake and release processes. This action may be correlated with the recently identified blocking properties of the compound on the sodium channels, as previously shown for local anaesthetics.

Further contribution to the study of corticostriatal glutamatergic and nigrostriatal dopaminergic interactions within the striatal network: an in vivo voltammetric investigation.

In vivo voltammetry was used in freely moving rats to study the processes whereby striatal dopamine (DA) release is regulated by corticostriatal glutamatergic neurons. Electrical stimulation of the cerebral cortex was found to markedly increase the striatal DA-related voltammetric signal amplitude. Similar enhancements have been observed after intracerebroventricular administration of 10nmoles glutamate, quisqualate and AMPA, whereas NMDA was found to decrease the amplitude of the striatal signals. The NMDA receptor antagonist APV did not significantly affect the voltammetric signal but prevented the NMDA-induced depression of the DA-related signals. These data are in agreement with those obtained in numerous previous studies suggesting that the glutamatergic corticostriatal neurons exert activatory effects on the striatal DA release via non-NMDA receptors. The mechanism involved might be of a presynaptic nature. The role of the NMDA receptors may however consist of modulating the dopaminergic transmission phasically and in a depressive way, which would be consistent with behavioural data suggesting the existence of a functional antagonism between the activity of the corticostriatal glutamatergic and nigrostriatal dopaminergic systems.

Pyridostigmine-induced inhibition of blood acetylcholinesterase (AChE) and resulting effects on manual ocular tracking performance in the trained baboon.

A method was developed to determine the effects of pyridostigmine on sensory-motor control in baboons trained to perform visuo-oculo-manual tracking tasks. The performance was evaluated in terms of accuracy, maximum smooth pursuit velocity, and gain. Administration of pyridostigmine (0.4-0.7 mg/kg intramuscularly) induced a dose-related decrease in smooth pursuit performance which appeared 10 to 30 min after injection and lasted about 1 h. If the animal was allowed to track the target with its hand or to move the target itself, the smooth pursuit performance increased significantly, returning to near normal values. The movement of the hand was not altered. The effect of intramuscular injections of pyridostigmine (0.5 mg/kg) was studied on blood acetylcholinesterase activity in alert baboons. Maximum inhibition of about 60% of baseline activity was observed 10 min after pyridostigmine injection. Subsequently the activity slowly tended to return to control level. Three hours after drug administration, acetylcholinesterase activity inhibition was still 34.1% of control value. In the baboon, the time-course of acetylcholinesterase activity recovery after injection is similar to that recorded in human. The similarity of the time-course of blood acetylcholinesterase activity and changes in smooth pursuit performance suggests a causal relationship between the two factors. A further experiment showed that pyridostigmine administered per os at a dose normally used as a prophylactic against organophosphates does not significantly alter sensorimotor performance as evaluated at the oculomanual tracking system level. When compared to the literature, our results suggest that the baboon can be used as a human experimental analog for pharmacological studies such as the action of acetylcholinesterase inhibitors.

Motor impairments and neurochemical changes after unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system in monkeys.

Unilateral lesions of the nigrostriatal dopaminergic system were induced in five monkeys by intranigral injections of the neurotoxin 6-hydroxydopamine. Following the lesion, all monkeys showed a transient reluctance in using the contralateral forelimb, accompanied, in two monkeys by semi-flexed posture of the disabled forelimb. Three of the monkeys that had been conditioned to perform a visually triggered goal-directed arm movement, showed an increase in latency and duration of contralateral arm movements. Task performance recovered spontaneously to preoperative levels within four months in two monkeys despite significant reductions of endogenous dopamine and dihydroxyphenylacetic acid contents in the caudate nucleus, putamen and globus pallidus ipsilateral to the neurotoxic nigral injection. The third monkey exhibited a persistent increase in movement latency associated with a near complete loss of dopamine in both the putamen and the caudate nucleus. In all cases, an increase the dihydroxyphenyl-acetic acid to dopamine ratio was detected in the striatum and pallidum suggesting a compensatory increase in dopamine turnover in remaining intact dopaminergic nerve terminals. The level of serotonin was changed in all monkeys consisting of either a decrease or an increase, depending on the striatopallidal regions studied. Changes in choline acetyltransferase and glutamic acid decarboxylase activities in the same regions were only seen in some cases. The present results show that 6-hydroxydopamine-induced partial unilateral lesion of nigral dopaminergic neurons produced predominantly contralateral hypokinesia, accompanied by reductions of dopamine content in the ipsilateral striatum and pallidum. The use of this locally applied neurotoxin appears to be a suitable method for investigating neurophysiological mechanisms underlying hypokinesia since deficits in both initiating and executing movements can be expressed independently of other behavioral symptoms. The results show more persistent deficits in starting movements than in their execution and thus suggest that motor initiation is more dependent upon the functional integrity of the nigrostriatal dopamine system than movement completion.

Putative neurotransmitters in the red nucleus and their involvement in postlesion adaptive mechanisms.

A variety of putative neurotransmitters has been described in the red nucleus (RN). Measurement of neurotransmitter biochemical markers and study of their specific localizations using morphological techniques in lesion and deafferentation of the RN indicate the participation of glutamate (Glu) in corticorubral transmission and the presence of GABA in RN intrinsic neurones. The cerebellorubral projection may contain at least two populations of fibres, the one using acetylcholine and the other Glu as neurotransmitter. The presence of a serotoninergic input was also demonstrated. Selective deafferentations of the RN, particularly from its cerebellar input, result in biochemical and immunohistochemical responses indicative of increased corticorubral glutamatergic and local GABAergic transmission. These adaptive changes of neuronal transmission as well as the previously described sprouting of corticorubral nerve terminals may contribute to functional recovery after cerebellectomy in adult animals.

Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum.

In vivo electrical stimulation of the frontal cortical areas was found to enhance sodium-dependent high-affinity glutamate uptake (HAGU) measured in rat striatal homogenates. This activating effect was counteracted by in vivo administration of apomorphine and by in vitro addition of dopamine (DA; 10(-8) M) in the incubation medium, and potentiated by in vivo haloperidol administration. At the doses used, the dopaminergic compounds had no effect on basal HAGU. alpha-Methylparatyrosine pretreatment was found to enhance slightly basal HAGU as well as the activating effects of cortical stimulation. Interestingly enough, lesion of dopaminergic neurons by substantia nigra injection of 6-hydroxydopamine (6-OHDA) did not cause any significant change either in basal HAGU or in the effect of cortical stimulation. Measurement of DA effects in vitro in experiments combined with in vivo manipulations of the dopaminergic nigrostriatal and corticostriatal systems showed that the capacity of DA to inhibit striatal HAGU depends directly on the level of the uptake activation reached over basal value. These results suggest that under physiological conditions, the dopaminergic nigrostriatal pathway exerts a modulatory presynaptic action on corticostriatal glutamatergic transmission, counteracting increasing glutamatergic activity. In the case of chronic DA depletion induced by 6-OHDA, striatal adaptations may occur modifying the mechanisms acting at corticostriatal nerve terminal level.

Comparative analysis of the effects of in vivo electrical stimulation of the frontal cortex and gamma-butyrolactone administration on dopamine and dihydroxyphenyl acetic acid (DOPAC) striatal contents in the rat.

The effects of an in vivo electrical stimulation of the frontal cortex were measured on dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) contents in the striatum of rats anesthetized with chloral hydrate. Results showed a large decrease in DOPAC and a marked increase in DA content, similar to that obtained when nigrostriatal dopaminergic neuron firing rate is reduced by ?-butyrolactone (GBL) administration. If electrical activation of the corticostriatal glutamatergic neurons increased DA release into the striatum as previously shown in cats, the results of the present experiments actually appeared to be paradoxical. Further studies on [(3)H]DA uptake, tyrosine hydroxylase activity, and measurement of serotonin and 5-hydroxyindole acetic acid after cortical stimulation underline the specificity of changes in DA and DOPAC levels. These data may thus suggest that parallel changes in DA and DOPAC striatal contents can be obtained either by activating DA release by presynaptic mechanisms or by decreasing the firing rate of the nigrostriatal dopaminergic neurons.

Effects of pyroglutamic acid on corticostriatal glutamatergic transmission.

The effects of L-pyroglutamic acid, a molecule structurally derived from L-glutamic acid (Glu), were measured on the high affinity of uptake of glutamic acid from striatal synaptosomes of the rat and on the binding of [L-3H]glutamic acid to striatal membranes. The results showed a competitive inhibition of the high affinity transport of glutamic acid by L-pyroglutamic acid in vitro with no effect on the uptake of gamma-aminobutyric acid (GABA). An inhibition of the binding of [L-3H]glutamic acid to striatal membranes was also detected. Significant high affinity uptake of [L-3H]pyroglutamic acid was evident in synaptosomes from the striatum. A regional distribution study of the uptake processes for [L-3H]glutamic acid and [L-3H]pyroglutamic acid in different areas of the brain showed a similar distribution, suggesting that an uptake of [L-3H]pyroglutamic acid, although weak, occurs in glutamatergic nerve terminals. This proposal was further reinforced by measuring the effects of a large cortical lesion involving frontal and parietal areas on the uptake of [L-3H]glutamic acid and [L-3H]pyroglutamic acid in synaptosomes from the striatum. The results showed a large decrease in the uptake processes of both labelled molecules showing that the uptake of [L-3H]pyroglutamic acid, as for glutamic acid mainly occurred in corticostriatal nerve terminals, although other uptake sites are not excluded.

Changes in choline acetyltransferase, glutamic acid decarboxylase, high-affinity glutamate uptake and dopaminergic activity induced by kainic acid lesion of the thalamostriatal neurons.

Kainic acid lesion of the 'centre médian'-parafascicular complex of the thalamus inducing a degeneration of the thalamostriatal neurons was followed by a decrease in choline acetyltransferase (ChAT) in the rostral part of the striatum in the rat. This decrease in ChAT was concomitant with an increase in glutamate decarboxylase, high-affinity glutamate uptake and apparent dopamine turnover. These results suggest that the thalamostriatal partly cholinergic input exerts a powerful control over GABAergic, glutamatergic and dopaminergic neurons in the basal ganglia.

High affinity glutamate uptake in the red nucleus and ventrolateral thalamus after lesion of the cerebellum in the adult cat: biochemical evidence for functional changes in the deafferented structures.

High affinity glutamate uptake (HAGU) was measured within the red nucleus (RN) and the ventrolateral thalamic area in intact adult cats and in animals which had undergone a large hemicerebellectomy 8 to 21 days before. In the side contralateral to the lesion, results show two types of changes in HAGU: 1. In the caudal parts of the RN and the ventrolateral thalamic nucleus (VL), a strong HAGU decrease was demonstrated suggesting some cerebellorubral and cerebellothalamic fibres use glutamate (Glu) as their neurotransmitter. 2. In the rostral parts of the RN and the VL, an increase in HAGU was detected. This increase was particularly large at thalamic level, which led us to perform a kinetic analysis of the uptake system. Results show that the increase observed in HAGU is related in the thalamic area to an increased affinity of the transport sites for Glu. The mechanism of the HAGU increase measured in the rostral VL after cerebellectomy was further investigated in the presence of acetylcholine (ACh) which we have previously shown to be possibly involved in the neurotransmission of some cerebellothalamic and cerebellorubral fibres. ACh was shown to exert an inhibitory effect on HAGU in the control situation. Decrease in affinity of the transport sites for Glu induced by ACh was more pronounced when HAGU was enhanced as a consequence of the cerebellar lesion. We hypothesized that the cerebellectomy enhances the activity of nerve terminals which take up Glu in the VL and that we have shown to be mainly related to corticothalamic neurons. The basic mechanism involved in this activation could be the withdrawal of presynaptic inhibitory controls on corticothalamic fibres due to the removal of the putative cholinergic cerebellar input. This hypothesis was extended to the RN where previous electrophysiological and anatomical studies have suggested that the cerebellar lesion induces a sprouting of corticorubral nerve terminals. The increase in HAGU in response to the cerebellar lesion could constitute an adaptive mechanism by which the CNS may compensate for the loss of the excitatory cerebellar input to the RN and thalamic neurons by increasing the corticofugal transmission.

Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum.

The high affinity glutamate uptake (HAGU) was measured in homogenates obtained from striata of control rats and animals submitted to electrical stimulation of the frontal cortical areas. Results show that the stimulation of the corticostriatal neurons induces an activation of the uptake of glutamate (Glu) in the striatum resulting from an increase in the affinity of the transport site for Glu. In other experiments we have obtained evidence that, when stimulated, presumed dopaminergic receptors can inhibit HAGU. The dopaminergic antagonist haloperidol was shown not to influence that basal Glu uptake but this neuroleptic highly potentiates the excitatory effects of cortical stimulations. The nigrostriatal dopaminergic pathway may exert a modulatory action on the corticostriatal glutamatergic neurons as it counteracts increasing glutamatergic activity.

Topographic changes in high-affinity glutamate uptake in the cat red nucleus, substantia nigra, thalamus, and caudate nucleus after lesions of sensorimotor cortical areas.

The distribution of presumed glutamatergic projections from sensorimotor cortical areas to the red nucleus (RN), the substantia nigra (SN), the ventrolateral thalamic complex, and the caudate nucleus (CN) was investigated in the cat. For this purpose, the changes in the sodium-dependent high-affinity glutamate uptake (HAGU) rate were measured in homogenates of tissue microdissected from various parts of these subcortical structures after chronic surgical ablation of sensorimotor cortical areas. After 8 to 10 days survival, significant reductions in HAGU activity were noted in the structures studied on the side ipsilateral to the operated cortex. Within each structure, various quantitative or qualitative changes were observed. Higher decreases in HAGU activity were found in the caudal part of the RN, the ventrolateral thalamic nucleus, and the dorsolateral part of the CN than in the other parts of these structures. The lateral part of the SN showed a large decrease in HAGU rate and its medial part a small but significant increase. Referring to the anatomic data concerning the organization of cortical projections from sensorimotor areas to the structures studied, it was shown that our results support the view that glutamate could act as a neurotransmitter along various corticosubcortical pathways.