Nicole Dusticier

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.

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.

Increased glutamate decarboxylase activity in the red nucleus of the adult cat after cerebellar lesions

Glutamate decarboxylase (GAD)activity, a marker for GABAergic structures, was studied in the cat red nucleus. GAD is more concentrated in the rostral than in the caudal third of the structure. GAD levels were measured after chronic unilateral lesions of the cerebellum. Destruction of the dentate area and of the nucleus interpositus induced increases of GAD in the contralateral but not in the ipsilateral red nucleus. Similar changes also occurred in the denervated nucleus ventralis lateralis (VL) and nucleus ventralis anterior (VA) of the thalamus. Results show that loss of the excitatory cerebellar input could lead to changes in inhibitory GABAergic nerve terminals. This increase may be induced transsynaptically within existing neurons or, more likely, additional GAD-containing nerve terminals may be formed by axonal sprouting.

Choline acetyltransferase activity in discrete regions of the cat brain

Choline acetyltransferase (CAT) activity was measured in the cat brain using a microdissection of the structures from frozen slices and an extremely sensitive radioisotopic assay for the enzyme. About 20 cerebral regions were chosen for study because of their role in sensorimotor integration. Highest CAT activity was found in the basal ganglia, followed by the thalamus and the cerebral cortex. The cerebellum had the lowest level of CAT. Special detailed studies were made in the substantia nigra, nucleus ventralis lateralis of the thalamus, areas 4 and 6 of the cerebral cortex, the red nucleus in the mesencephalon and the deep cerebellar nuclei in order to define the intranuclear distribution of their cholinergic innervation.

Changes in dopamine release in caudate nuclei and substantia nigrae after electrical stimulation of the posterior interposate nucleus of cat cerebellum

The effect of unilateral electrical stimulation of the posterior interposate nucleus of the cerebellum was examined on the activity of the nigro-striatal dopaminergic pathways on both sides of the brain in alpha-chloralose anaesthetized cats. Push-pull cannulae were inserted into both caudate nuclei and both substantia nigrae to measure the release of [3H]dopamine ( [3H]DA) which was continuously synthesized from L-[3,5-3H]tyrosine. The stimulation of the cerebellum induced long-lasting well-organized changes in [3H]DA release in the four structures: an increased release of the neurotransmitter in both the contralateral caudate nucleus and the ipsilateral substantia nigra and a reduction in the release of DA from the ipsilateral caudate nucleus and the contralateral substantia nigra. This finding supports the concept of a functional interaction between the cerebellum and the basal ganglia.

Effects of α-chloralose on the activity of the nigrostriatal dopaminergic system in the cat

Abstract The effects of α-chloralose anaesthesia were studied in the cat on the release of 3 H-dopamine ( 3 H-DA) from the caudate nucleus and the substantia nigra using the push-pull cannula method and continuous labelling of the structures with L-3,5- 3 H-tyrosine. Results were compared to those obtained under the same experimental conditions in both halothane-anaesthetized animals and ‘encephale isole’ preparations. The α-chloralase-anaesthetized preparation showed the lowest level of 3 H-DA release, both from dopaminergic nerve terminals in the caudate nucleus and from dendrites of dopaminergic neurons in the substantia nigra. Furthermore, the time required to reach a steady-state release of 3 H-DA was longer in α-chloralose-anaesthetized cats than in animals under halothane. This indicated that the activity of the dopaminergic neurons is depressed under α-chloralose anaesthesia. In the second part of the study, we measured the effects of unilateral somatic stimulation on the release of 3 H-DA from the caudate nuclei and substantiae nigrae on both sides of the brain. The results show that under α-chloralose anaesthesia, the electrical stimulation of the paw of the right forelimb does not significantly affect the release of 3 H-DA from any of the above four structures. This contrasts with the changes of 3 H-DA release seen in the same experimental conditions under halothane anaesthesia.

Brain glutamate uptake: Regional distribution study from sensorimotor areas in the cat

Regional distribution of glutamatergic activity was studied in the sensorimotor areas of the cats brain, using microdissection of the structures and the high affinity glutamate uptake (HAGU) estimation as an index. For this purpose a procedure allowing the measurement of HAGU activity in sucrose homogenates of the microsamples dissected from refrigerated slices was developed. The highest glutamatergic activity was found in the ventral parts of the thalamus, followed by the caudate nucleus and the cerebral cortex. The mesencephalic structures showed the lowest glutamate (Glu) transport capacities among the regions of gray matter studied. Intranuclear investigations were carried out within the substantia nigra, the caudate nucleus and the red nucleus. Rostrocaudal variations in HAGU activity were shown within the red nucleus while no significant topographical variations were detected either in the substantia nigra or in the caudate nucleus.