Blockade of N -methyl- d -aspartate receptor activation suppresses learning-induced synaptic elimination

Abstract

Auditory filial imprinting in the domestic chicken is accompanied by a dramatic loss of spine synapses in two higher associative forebrain areas, the mediorostral neostriatum͞hyperstriatum ventrale (MNH) and the dorsocaudal neostriatum (Ndc). The cellular mechanisms that underlie this learning-induced synaptic reorganization are unclear. We found that local pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors in the MNH, a manipulation that has been shown previously to impair auditory imprinting, suppresses the learning-induced spine reduction in this region. Chicks treated with the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) during the behavioral training for imprinting (postnatal day 0-2) displayed similar spine frequencies at postnatal day 7 as naive control animals, which, in both groups, were significantly higher than in imprinted animals. Because the average dendritic length did not differ between the experimental groups, the reduced spine frequency can be interpreted as a reduction of the total number of spine synapses per neuron. In the Ndc, which is reciprocally connected with the MNH and not directly inf luenced by the injected drug, learning-induced spine elimination was partly suppressed. Spine frequencies of the APVtreated, behaviorally trained but nonimprinted animals were higher than in the imprinted animals but lower than in the naive animals. These results provide evidence that NMDA receptor activation is required for the learning-induced selective reduction of spine synapses, which may serve as a mechanism of information storage specific for juvenile emotional learning events.Spines are considered specialized structures subserving a biochemical compartmentalization to provide a protected microenvironment for calcium and other messengers and, therefore, to play a key role in the expression of synaptic plasticity (1-5). Changes in the numerical density of spine synapses are proposed to represent a principal cellular correlate of learning and memory formation (6-12). Auditory filial imprinting in the domestic chicken is associated with a reduction of spine synapses in two associative forebrain areas, the mediorostral neostriatum͞hyperstriatum ventrale (MNH) and the reciprocally connected dorsocaudal neostriatum (Ndc) (8,(12)(13)(14), an area that provides indirect auditory input into the MNH (15). Based on anatomical criteria, such as its glutamatergic thalamic afferents and its tegmental dopaminergic inputs, the MNH may be considered as the avian analogue of the mammalian prefrontal cortex, whereas the Ndc seems to correspond to second-order parasensory association areas in the mammalian parietotemporal cortex (15-17).The cellular and molecular mechanisms that trigger, regulate, and mediate proliferative and regressive changes of synaptic density in the course of this juvenile learning event are unclear. Although there is convincing evidence that activation of N-methyl-D-aspartate (NMDA) receptors is a key step in learning and memory formation (18-28) and t...

Immunocytochemical localization of ionotropic glutamate receptors subunits in the adult quail forebrain

“…The presence of glutamate receptor subunits in this brain area is in agreement with the large amount of literature that demonstrates the crucial role played by glutamate in the long-term potentiation (LTP), a process that was discovered and takes place in a prominent manner in the hippocampus (Morris et al, 1986;Steele et al, 1995;Bock and Braun, 1999). LTP is a long-lasting synaptic enhancement caused by the repeated activation of excitatory synapses.…”

N-methyl-D-aspartate receptor-mediated modulation of monoaminergic metabolites and amino acids in the chick forebrain: Anin vivo microdialysis and electrophysiology study

“…These experiments demonstrated that the activation of NMDA receptors is required for auditory filial imprinting (Bock et al, 1996), for the induction of long-term potentiation-like potentiation (Wang et al, 1994), and for the learninginduced synaptic reorganization (Bock and Braun, 1999). Our results presented here indicate that the activation of this receptor, which normally occurs via activation of glutamatergic afferents from the dorsomedial thalamus (Metzger et al, 1996b), may induce a suppression of the dopaminergic system arising from ventral tegmental afferents (Metzger et al, 1996b), and of the serotonergic system from nuclei raphe afferents (Metzger et al, 1996a).…”

Correlates of intellectual ability with morphology of the hippocampus and amygdala in healthy adults

“…During early postnatal life, apoptosis (Simonati, Rosso, & Rizzuto, 1997;Williams & Rakic, 1988) and pruning of both redundant neuronal processes and non-functional dendritic synapses (Herschkowitz, 1988;Huttenlocher, 1979;Huttenlocher, De Courten, Garey, & van der Loos, 1982;Purves & Lichtman, 1980) are probably the most significant determinants of regional volumes. By eliminating redundant neuronal processes, dendritic branches, and supernumerary synaptic spines, pruning supports learning and development of psychomotor skills (Bock & Braun, 1998;Bock & Braun, 1999;Nixdorf-Bergweiler, Wallhausser-Franke, & DeVoogd, 1995;Rakic, Bourgeois, & Goldman-Rakic, 1994;Rausch & Scheich, 1982;Rollenhagen & Bischof, 1994;Wallhausser & Scheich, 1987). Moreover, human postmortem studies of the cerebral cortex have demonstrated a 40-50% decrease in synaptic density in frontal and parietal cortices between infancy and late adolescence (Huttenlocher, 1979;Huttenlocher, 1984;Huttenlocher & de Courten, 1987).…”