Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study

Abstract

SUMMARY1. The responses ofPurkinje cells to short duration (pulse) ionophoretic applications of L-aspartate (L-asp), L-glutamate (L-glu), N-methyl DL-aspartate (NMDLA) and quisqualic acid in their dendritic fields were studied in vitro on sagittal slices of lobules IX and X of the adult rat cerebellum.2. Pulse application of L-asp or L-glu evoked transient and dose-dependent increases in the firing rate of the simple spikes recorded extracellularly as single units. When the ionophoretic electrode was positioned in the dendritic field of the Purkinje cells, the lowest thresholds for L-glu and L-asp mediated excitations of the cells were as low as 25 and 35 pC respectively, with a latency for maximal responses as brief as 7 ms.3. In intracellular recordings these excitatory responses consisted ofdepolarizations of up to 18 mV in amplitude and with depolarizing slopes up to 0-52 mV/ms. They were generally unaccompanied by changes in cell input resistance in contrast to the marked decrease which occurred in response to steady applications of large doses of L-asp and L-glu.4. The spatial distribution of the excitatory sites confirmed that the dendritic sensitivity to L-glu was greater than that of the soma and showed that the same was true for L-asp. In 34 % of cells the sensitivity for L-asp declined markedly in the upper region of the molecular layer, whereas it remained high for L-glu; no such differential sensitivity was detected in the remaining 66 % of cells. F. CREPEL, S. S. DHANJAL AND T. A. SEARS greater and its action more prolonged. Furthermore, its steady application led to an abrupt and marked decrease in cell membrane resistance.8. The excitatory effects of L-asp, L-glu and quisqualic acid were antagonized by L-glutamic acid diethyl ester more consistently than by D-oz-aminoadipate, suggesting together with previous observations that L-asp and L-glu act on Purkinje cells via quisqualic acid rather than via NMDLA receptors.

NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell

“…This is further supported by the existence of an NMDA-mediated component in the CF-EPSC. However, considerable previous evidence indicated that NMDA-Rs are not, or very weakly, expressed by adult Purkinje cells (Crepel et al, 1982;Garthwaite et al, 1987;Konnerth et al, 1990;Krupa and Crepel, 1990;Farrant and Cull-Candy, 1991;Llano et al, 1991). If this is true, the NMDA-mediated CF-EPSC evidenced here has to be of presynaptic origin.…”

d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

“…Tendril collaterals of climbing fibers project to Purkinje cell bodies near their axons (Palay and Chan-Palay, 1974). Physiological studies have demonstrated that glutamate or aspartate from parallel fibers acts on NMDA receptors located on basket cell dendrites to increase GABA release, because the application of NMDA onto adult cerebellar Purkinje cells produces inhibitory responses that are blockable by bicuculline (Crepel et al, 1982;Quinlan and Davies, 1985;Llano et al, 1991). Climbing fiber tendril collaterals near NMDA receptors on basket cell axons could mediate a similar response.…”

Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum

“…Moreover, the present study revealed that glutamate-induced vasoconstrictions are insensitive to NMDA receptor antagonism. Finally, Purkinje cells do not express functional NMDA receptors (Crepel et al, 1982), and, in contrast to glutamate, NMDA does not stimulate arachidonic acid release from astrocytes (Stella et al, 1994). Therefore, slices were stimulated with NMDA to assess the contribution of endogenously released neuronal NO in cerebellar dilation.…”

“…We found a greater release of NO in slices stimulated with glutamate compared with NMDA, indicating activation of non-NMDA receptors in the glutamate-induced NO release. Indeed, stellate cells, which express NMDA receptors (Rancillac and Crepel, 2004) whereas Purkinje (Crepel et al, 1982) and glial (Stella et al, 1994) cells do not, also express Ca 2ϩ -permeable AMPA receptors (Liu and Cull-Candy, 2000) and group I mGluRs (Grandes et al, 1994;Karakossian and Otis, 2004), and their concurrent activation by glutamate most likely explains, at least in part, the larger amounts of NO released by glutamate compared with NMDA. Yet, this larger NO release translated into cerebellar constrictions and not dilations, suggesting that the constriction elicited by the synthesis and release of contractile arachidonic acid derivatives from glia and/or neurons and of endothelin-1 from Purkinje cells predominates over the NO-induced dilation (Fig.…”