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EphB2 receptor cell-autonomous forward signaling mediates auditory memory recall and learning-driven spinogenesis.

ABSTRACT: While ephrin-B ligands and EphB receptors are expressed to high levels in the learning centers of the brain, it remains largely unknown how their trans-synaptic interactions contribute to memory. We find that EphB2 forward signaling is needed for contextual and sound-evoked memory recall and that constitutive over-activation of the receptor's intracellular tyrosine kinase domain results in enhanced memory. Loss of EphB2 expression does not affect the number of neurons activated following encoding, although a reduction of neurons activated after the sound-cued retrieval test was detected in the auditory cortex and hippocampal CA1. Further, spine density and maturation was reduced in the auditory cortex of mutants especially in the neurons that were dual-activated during both encoding and retrieval. Our data demonstrates that trans-synaptic ephrin-B-EphB2 interactions and forward signaling facilitate neural activation and structural plasticity in learning-associated neurons involved in the generation of memories.

SUBMITTER: Talebian A

PROVIDER: S-EPMC6789002 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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EphB2 receptor cell-autonomous forward signaling mediates auditory memory recall and learning-driven spinogenesis.

Talebian Asghar A Henkemeyer Mark M

Communications biology 20191011

While ephrin-B ligands and EphB receptors are expressed to high levels in the learning centers of the brain, it remains largely unknown how their trans-synaptic interactions contribute to memory. We find that EphB2 forward signaling is needed for contextual and sound-evoked memory recall and that constitutive over-activation of the receptor's intracellular tyrosine kinase domain results in enhanced memory. Loss of EphB2 expression does not affect the number of neurons activated following encodin ...[more]

PMID: 31633063

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Project description:Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long-term memory formation is scarce. Our previous pharmacological studies on cortex-dependent frequency-modulated tone-sweep discrimination learning of Mongolian gerbils showed that auditory-cortical D1/5 -dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5 -dopamine receptors and ?-adrenoceptors, we hypothesised a role of ?-adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the ?1/2 -adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post-session time window. When applied to the auditory cortex 1 day before initial conditioning, ?1 -adrenoceptor-antagonising and ?1 -adrenoceptor-stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas ?2 -selective drugs were ineffective. In contrast, single-sweep detection learning was normal after propranolol infusion. By immunohistochemistry, ?1 - and ?2 -adrenoceptors were identified on the neuropil and somata of pyramidal and non-pyramidal neurons of the gerbil auditory cortex. The present findings suggest that ?-adrenergic signalling in the auditory cortex has task-related importance for discrimination learning of complex sounds: as previously shown for D1/5 -dopamine receptor signalling, ?-adrenoceptor activity supports long-term memory consolidation and reconsolidation; additionally, tonic input through ?1 -adrenoceptors may control mechanisms permissive for memory acquisition.

Dataset Information

EphB2 receptor cell-autonomous forward signaling mediates auditory memory recall and learning-driven spinogenesis.

Publications

EphB2 receptor cell-autonomous forward signaling mediates auditory memory recall and learning-driven spinogenesis.

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