Role of glutamate δ-2 receptors in activity-dependent competition between heterologous afferent fibers

Morando, Laura; Cesa, Roberta; Rasetti, Roberta; Harvey, Richard F.; Strata, Piergiorgio

doi:10.1073/pnas.171098398

Cited by 60 publications

(64 citation statements)

References 31 publications

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“…More recently, the capacity to learn and to retain fear conditioned responses has been investigated in hotfoot mutant mice ( Sacchetti et al, 2004). These animals are characterized by a primary deficiency of the synapses made by the parallel fibers (PFs) onto the Purkinje cells (PCs) ( Yamazaki et al 1992, Morando et al 2001, Yuzaki 2003and Mandolesi et al 2009. In these mutant mice, although the cerebellar dysfunction does not affect acquisition of the conditioned motor response ( Fig.…”

Section: Cerebellar Vermis and Fear Conditioning In Animal Studiesmentioning

confidence: 99%

Cerebellum and emotional behavior

Sacchetti¹,

Scelfo²,

Strata³

2009

Neuroscience

129

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Fear conditioning involves learning that a previously neutral stimulus (CS) predicts an aversive unconditioned stimulus (US). Lesions of the cerebellar vermis may affect fear memory without altering baseline motor/autonomic responses to the frightening stimuli. Reversible inactivation of the vermis during the consolidation period impairs retention of fear memory. In patients with medial cerebellar lesions conditioned bradycardia is impaired. In humans, cerebellar areas around the vermis are activated during mental recall of emotional personal episodes, if a loved partner receives a pain stimulus, and during learning of a CS-US association. Moreover, patients with cerebellar stroke may fail to show overt emotional changes. In such patients, however, the activity of several areas, including ventromedial prefrontal cortex, anterior cingulate, pulvinar and insular cortex, is significantly increased relative to healthy subjects when exposed to frightening stimuli. Therefore, other structures may serve to maintain fear response after cerebellar damage. These data indicate that the vermis is involved in the formation of fear memory traces. We suggest that the vermis is not only involved in regulating the autonomic/motor responses, but that it also participates in forming new CS-US associations thus eliciting appropriate responses to new stimuli or situations. In other words, the cerebellum may translate an emotional state elaborated elsewhere into autonomic and motor responses.

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Section: Cerebellar Vermis and Fear Conditioning In Animal Studiesmentioning

confidence: 99%

Cerebellum and emotional behavior

Sacchetti¹,

Scelfo²,

Strata³

2009

Neuroscience

129

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“…We did not attempt to clone mGluR6 and mGluR7, because mammalian mGluR6 is known to be expressed in only the retina (Nakajima et al, 1993), and mGluR6 and -7 were too close in sequence to be distinguished reliably by initial PCR or by in situ hybridization. We did not attempt to clone the NMDA receptor subunit NR3B, because it was just being characterized at the time when we began our study (Nishi et al, 2001), or delta 1 and delta 2 subunits, because these are known to be involved mainly in cerebellar function (Morando et al, 2001). Without fail, we found all 21 glutamate receptor subunits/subtypes in the zebra finch brain.…”

Section: Songbird Glutamate Receptorsmentioning

confidence: 99%

Differential expression of glutamate receptors in avian neural pathways for learned vocalization

Wada

Sakaguchi

Jarvis

et al. 2004

J of Comparative Neurology

140

188

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Learned vocalization, the substrate for human language, is a rare trait. It is found in three distantly related groups of birds-parrots, hummingbirds, and songbirds. These three groups contain cerebral vocal nuclei for learned vocalization not found in their more closely related vocal nonlearning relatives. Here, we cloned 21 receptor subunits/subtypes of all four glutamate receptor families (AMPA, kainate, NMDA, and metabotropic) and examined their expression in vocal nuclei of songbirds. We also examined expression of a subset of these receptors in vocal nuclei of hummingbirds and parrots, as well as in the brains of dove species as examples of close vocal nonlearning relatives. Among the 21 subunits/subtypes, 19 showed higher and/or lower prominent differential expression in songbird vocal nuclei relative to the surrounding brain subdivisions in which the vocal nuclei are located. This included relatively lower levels of all four AMPA subunits in lMAN, strikingly higher levels of the kainite subunit GluR5 in the robust nucleus of the arcopallium (RA), higher and lower levels respectively of the NMDA subunits NR2A and NR2B in most vocal nuclei and lower levels of the metabotropic group I subtypes (mGluR1 and -5) in most vocal nuclei and the group II subtype (mGluR2), showing a unique expression pattern of very low levels in RA and very high levels in HVC. The splice variants of AMPA subunits showed further differential expression in vocal nuclei. Some of the receptor subunits/subtypes also showed differential expression in hummingbird and parrot vocal nuclei. The magnitude of differential expression in vocal nuclei of all three vocal learners was unique compared with the smaller magnitude of differences found for nonvocal areas of vocal learners and vocal nonlearners. Our results suggest that evolution of vocal learning was accompanied by differential expression of a conserved gene family for synaptic transmission and plasticity in vocal nuclei. They also suggest that neural activity and signal transduction in vocal nuclei of vocal learners will be different relative to the surrounding brain areas.

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“…This finding led to the hypothesis that in the absence of activity, the PC is intrinsically endowed with cues to be innervated by the PFs. The CFs, to achieve and maintain their dendritic territory, have to be active to displace the cues of the excitatory competitor afferents (6)(7)(8).…”

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confidence: 99%

“…Therefore, a first aim of this article is to discover whether the inhibitory input is also involved in the activity-dependent competition for the PC innervation. In addition, following the prolonged administration of TTX, a synapse made by GABAergic terminals onto the recently formed PC spines appear in the proximal dendrites, spines that normally receive an excitatory input (6). This surprising observation has prompted us to study the glutamate and GABA receptor distribution in the GABAergic terminal-PC synapses, both on the shaft and on the spines.…”

mentioning

confidence: 99%

Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

Cesa

Morando

Strata

2008

Proc. Natl. Acad. Sci. U.S.A.

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Competition among different axons to reach the somatodendritic region of the target neuron is an important event during development to achieve the final architecture typical of the mature brain. Trasmitter-receptor matching is a critical step for the signaling between neurons. In the cerebellar cortex, there is a persistent competition between the two glutamatergic inputs, the parallel fibers and the climbing fibers, for the innervation of the Purkinje cells. The activity of the latter input is necessary to maintain its own synaptic contacts on the proximal dendritic domain and to confine the parallel fibers in the distal one. Here, we show that climbing fiber activity also limits the distribution of the GABAergic input in the proximal domain. In addition, blocking the activity by tetrodotoxin infusion in Wistar rat cerebellum, a synapse made by GABAergic terminals onto the recently formed Purkinje cell spines appear in the proximal dendrites. The density of GABAergic terminals is increased, and unexpected double symmetric/asymmetric postsynaptic densities add to the typical symmetric phenotype of the GABAergic shaft synapses. Moreover, glutamate receptors appear in these ectopic synapses even in the absence of glutamate transmitter inside the presynaptic terminal and close to GABA receptors. These results suggest that the Purkinje cell has an intrinsic tendency to develop postsynaptic assemblies of excitatory types, including glutamate receptors, over the entire dendritic territory. GABA receptors are induced in these assemblies when contacted by GABAergic terminals, thus leading to the formation of hybrid synapses.cerebellum ͉ GABA receptor ͉ spinogenesis ͉ synaptic plasticity

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Role of glutamate δ-2 receptors in activity-dependent competition between heterologous afferent fibers

Cited by 60 publications

References 31 publications

Cerebellum and emotional behavior

Cerebellum and emotional behavior

Differential expression of glutamate receptors in avian neural pathways for learned vocalization

Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

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