Chemical anatomy of excitatory endings in the dorsal cochlear nucleus of the rat: Differential synaptic distribution of aspartate aminotransferase, glutamate, and vesicular zinc

Rubio, María E.; Juı́z, José M.

doi:10.1002/(sici)1096-9861(19980928)399:3<341::aid-cne4>3.0.co;2-0

Cited by 52 publications

(32 citation statements)

References 100 publications

(126 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results suggest that the deficit in fear memory in ZnT3 KO mice did not result from possible abnormalities in the basal levels of pain to the electric shock, anxiety, or depression. The absence of ZnT3 potentially might affect hearing in the mutants, because ZnT3 is present in the excitatory terminals of the dorsal cochlear nucleus (Frederickson 1989;Rubio and Juiz 1998;Cole et al 1999). Thus, a possibility exists that our fearconditioning observations based on freezing in response to the tone might be due to hearing abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

Martel¹,

Hevi²,

Friebely³

et al. 2010

Learn. Mem.

View full text Add to dashboard Cite

Synaptically released Zn2+ is a potential modulator of neurotransmission and synaptic plasticity in fear-conditioning pathways. Zinc transporter 3 (ZnT3) knock-out (KO) mice are well suited to test the role of zinc in learned fear, because ZnT3 is colocalized with synaptic zinc, responsible for its transport to synaptic vesicles, highly enriched in the amygdala-associated neural circuitry, and ZnT3 KO mice lack Zn 2+ in synaptic vesicles. However, earlier work reported no deficiency in fear memory in ZnT3 KO mice, which is surprising based on the effects of Zn 2+ on amygdala synaptic plasticity. We therefore reexamined ZnT3 KO mice in various tasks for learned and innate fear. The mutants were deficient in a weak fear-conditioning protocol using single tone -shock pairing but showed normal memory when a stronger, five-pairing protocol was used. ZnT3 KO mice were deficient in memory when a tone was presented as complex auditory information in a discontinuous fashion. Moreover, ZnT3 KO mice showed abnormality in trace fear conditioning and in fear extinction. By contrast, ZnT3 KO mice had normal anxiety. Thus, ZnT3 is involved in associative fear memory and extinction, but not in innate fear, consistent with the role of synaptic zinc in amygdala synaptic plasticity.

show abstract

Section: Discussionmentioning

confidence: 99%

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

Martel¹,

Hevi²,

Friebely³

et al. 2010

Learn. Mem.

View full text Add to dashboard Cite

show abstract

“…In the dorsal nuclei there is a peripheral punctate staining pattern in both cells and fibers, especially in the molecular layer. This region is also intensely stained by Timm histochemistry, a technique that detects zinc associated to glutamatergic terminals (Frederickson et al, 1988) Moreover, the molecular layer of the dorsal cochlear nucleus is an endpoint of numerous terminals coming from the auditory nerve, the intrinsic granule cells and other areas of the primary auditory pathway (Rubio and Juiz, 1998). It would be worthwhile to know what kind of functional relationship may exist between these neurochemical characteristics of the dorsal cochlear nuclei and the coincident MVa expression.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of myosin va in the adult rat brain

et al. 2003

View full text Add to dashboard Cite

Abstract-Brain myosin Va (MVa) is a molecular motor associated with plastic changes during development. MVa has previously been detected in the cell body and in dendrites of neuronal cells in culture, in cells of the guinea-pig cochlea, as well as in cerebellar cells. Adult Wistar rats (n‫,)41؍‬ 250 -300 g, were perfused with standard methods for immunohistochemistry, using a polyclonal, affinity-purified rabbit antibody against MVa tail domain. Anti-MVa antibody specifically stained neuronal nuclei from forebrain to cerebellar regions, and more intensely sensory nuclei. Differences in MVa immunoreactivity were detected between brain nuclei, ranging from very intense to weak staining. The analysis of MVa and glial fibrillary acidic protein staining in adjacent brain sections demonstrated a clear-cut neuronal labeling rather than an astroglial staining. The studies presented here represent a comprehensive map of MVa regional distribution in the CNS of the adult rat and may contribute to the basic understanding of its role in brain function and plasticity, particularly in relationship to phenomena that involve molecular motors, such as neurite outgrowth, organelle transport and neurotransmitter-vesicle cycling. It is important to highlight that this is a pioneer immunohistochemical study on the distribution of MVa on the whole brain of adult rats, a first step toward the understanding of its function in the CNS.

show abstract

“…In particular, fusiform cells receive zinc-rich PF input at their apical dendrites in the molecular layer, and zinc-lacking auditory nerve (AN) input at their basal dendrites in the deep layer (Fig. 3E) (32). Moreover, fusiform cells express AMPARs containing GluA2-3 subunits in their apical dendrites, whereas cartwheel cells express GluA1-3 subunits (33).…”

Section: Evoked Action Potential Driven Release Of Zinc From Presynapticmentioning

confidence: 99%

AMPA receptor inhibition by synaptically released zinc

Kalappa

Anderson

Goldberg

et al. 2015

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

110

149

View full text Add to dashboard Cite

The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.AMPA receptors | zinc | ZnT3 | synaptic plasticity | auditory T he development, function, and experience-dependent plasticity of the mammalian brain depend on the refined neuronal interactions that occur in synapses. In the majority of excitatory synapses, the release of the neurotransmitter glutamate from presynaptic neurons opens transmembrane ion channels in postsynaptic neurons, the ionotropic glutamate receptors, thereby generating the flow of excitatory signaling in the brain. As a result, these receptors play a fundamental role in normal function and development of the brain, and they are also involved in many brain disorders (1).The ionotropic glutamate receptor family consists of AMPA, kainate, and NMDA receptors (NMDARs). Although kainate receptor-mediated excitatory postsynaptic responses occur in a few central synapses (2), AMPA receptors (AMPARs) and NMDARs are localized in the postsynaptic density of the vast majority of glutamatergic synapses in the brain, mediating most of excitatory neurotransmission (1). NMDAR function is regulated by a wide spectrum of endogenous allosteric neuromodulators that fine-tune synaptic responses (3-5); however, much less is known about endogenous AMPAR neuromodulators [(1, 5), but see refs. 6 and 7]. Recent structural studies revealed that the amino terminal domain (ATD) and ligand-binding domain (LBD) are tightly packed in NMDARs but not AMPARs (8-10). These structural differences explain some of the functional differences in allosteric modulation between AMPARs and NMDARs, such as why the ATD of NMDARs, unlike that of AMPARs, modulates function and contains numerous binding sites for allosteric regulators. Nonetheless, given the importance of fine-tuning both synaptic AMPAR and NMDAR responses for brain function, it is puzzling that there is not much evidence for endogenous, extracellular AMPAR modulation. The discovery and establishment of endogenous AMPAR modulators is crucial both for understanding ionotropic glutamate receptor signaling and for developing therapeutic agents for the treatment of AMPAR-related disorders, such as d...

show abstract

Chemical anatomy of excitatory endings in the dorsal cochlear nucleus of the rat: Differential synaptic distribution of aspartate aminotransferase, glutamate, and vesicular zinc

Cited by 52 publications

References 100 publications

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

Immunohistochemical localization of myosin va in the adult rat brain

AMPA receptor inhibition by synaptically released zinc

Contact Info

Product

Resources

About