Sensitivity of rubrospinal neurons to excitatory amino acids in the rat red nucleus in vivo.
ABSTRACT Responses of rubrospinal neurons (RSNs) to iontophoretic applications of L-glutamate (L-Glu), L-aspartate (L-Asp), quisqualate (Quis) and N-methyl-D-aspartate (NMDA) have been studied in the rat red nucleus (RN) in vivo. All agonists produced a dose-dependent increase of the firing rate and Quis was found to be the most efficient. The responses to NMDA and to a lesser extent to L-Asp were abolished by steady application of 2-amino-5-phosphonovalerate (2APV) whereas responses to Quis were unaffected and those to L-Glu poorly antagonized. On the other hand, NMDA-mediated excitations were insensitive to steady application of 6,7-dinitroquinoxaline-2,3-dione (DNQX) which abolished responses to Quis and to a lesser extent to L-Glu while those to L-Asp were less affected. These results show the presence of both NMDA and non-NMDA receptors on RSNs in the rat. A specific localization of the NMDA receptors on distal dendrites of these neurons is suggested.
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ABSTRACT: NMDA receptors play key roles in synaptic plasticity and neuronal development, and may be involved in learning, memory, and compensation following injury. A polyclonal antibody that recognizes four of seven splice variants of NMDAR1 was made using a C-terminus peptide (30 amino acid residues). NMDAR1 is the major NMDA receptor subunit, found in most or all NMDA receptor complexes. On immunoblots, this antibody labeled a single major band migrating at M(r) = 120,000. The antibody did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues. Immunostained vibratome sections of rat tissue showed labeling in many neurons in most structures in the brain, as well as in the cervical spinal cord, dorsal root and vestibular ganglia, and in pineal and pituitary glands. Staining was moderate to dense in the olfactory bulb, neocortex, striatum, some thalamic and hypothalamic nuclei, the colliculi, and many reticular, sensory, and motor neurons of the brainstem and spinal cord. The densest stained cells included the pyramidal and hilar neurons of the CA3 region of the hippocampus, Purkinje cells of the cerebellum, supraoptic and magnocellular paraventricular neurons of the hypothalamus, inferior olive, red nucleus, lateral reticular nucleus, peripheral dorsal cochlear nucleus, and motor nuclei of the lower brainstem and spinal cord. Ultrastructural localization of immunostaining was examined in the hippocampus, cerebral cortex, and cerebellar cortex. The major staining was in postsynaptic densities apposed by unstained presynaptic terminals with round or mainly round vesicles, and in associated dendrites. The pattern of staining matched that of previous in situ hybridization but differed somewhat from that of binding studies, implying that multiple types of NMDA receptors exist. Comparison with previous studies of localization of other glutamate receptor types revealed that NMDAR1 may colocalize with these other types in many neurons throughout the nervous system.Journal of Neuroscience 03/1994; 14(2):667-96. · 6.75 Impact Factor
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ABSTRACT: The red nucleus (RN) has been widely used to study the formation and remodeling of synaptic connections during development and in post-lesion plasticity. Since glial cells are thought to contribute to synaptic plasticity, and information on functional properties of brain stem glia is missing, we analyzed voltage-gated ion channels as well as glutamate receptors expressed by glial cells of the RN. The patch-clamp technique was applied to identified cells in acute brain stem slices of 5- to 12-days-old rats. Based on their pattern of membrane currents, two types of glial cells could be distinguished. A first type was characterized by passive, symmetrical currents. The second population of cells, which was the focus of the present study, expressed a complex pattern of voltage-gated channels. These cells could be labeled with antibodies against glutamine synthetase and S100 beta, suggesting an astroglial origin. Depolarizing voltage steps activated transient and delayed rectifier K+ currents as well as Na+ currents. In addition, a subset of cells expressed Ba2+ sensitive inward rectifier K+ currents activated by hyperpolarization. All "complex" glial cells analyzed possessed ionotropic glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype, while functional kainate and N-methyl-D-aspartate (NMDA) receptors could not be detected. Receptor activation blocked outward rectifying K+ currents, similar to previous observations in glial cells of the hippocampus and the corpus callosum.Glia 04/1997; 19(3):234-46. · 5.47 Impact Factor
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ABSTRACT: The effects of 5-hydroxytryptamine (5-HT) on the inhibitory responses evoked by γ-aminobutyric acid (GABA) in neurons of the red nucleus (RN) were studied using a microiontophoretic technique. Extracellular unitary recordings performed in anesthetized rats demonstrated that 5-HT ejection influencedGABA-evoked inhibition in 94% of RN neurons, enhancing them in 52% and depressing them in 46% of cases. Both effects were specific and dose-dependent,although enhancements or depressionsof the GABA responses were respectively inversely and directly related to the doses of 5-HT applied. The type of modulation exerted by 5-HT on the GABA responses was independent of the action of the amine on background firing. In fact, 5-HT induced an enhancement of the GABA responses in neurons mostly located in the rostral RN and a depression in those in the caudal RN. The application of 8-hydroxy-2(di-n-propylamino)tetralin, a specific 5-HT1A receptor agonist, enhanced GABA responses, whereas α-methyl-5-hydroxytryptamine, a 5-HT2A receptor agonist, depressed them. Both the 5-HT2 antagonist methysergide and the 5-HT2A selective antagonist ketanserin were able to block partially or totally the depressive action of 5-HT on GABA responses. In contrast, the same 5-HT antagonists mimicked the enhancing action of 5-HT on the GABA responses or were ineffective. Application of bicuculline, a GABAA receptor antagonist, enhanced the excitatory action of 5-HT on the background firing and slightly reduced the inhibitory action. It is concluded that 5-HT is able to modulate GABA-evoked responses in RN neurons by acting on both 5-HT1A and 5-HT2A receptors. The functional significance of a serotonergic control on GABAergic inhibitory effects in RN is discussed.Experimental Neurology 02/2001; · 4.62 Impact Factor