Enhanced TrkA signaling impairs basal forebrain-dependent behavior

Laura Calvo-Enrique; Silvia Lisa; Cristina Vicente-García; Ruben Deogracias; Juan Carlos Arévalo

doi:10.3389/fnmol.2023.1266983

Enhanced TrkA signaling impairs basal forebrain-dependent behavior

Front Mol Neurosci. 2023 Sep 22:16:1266983. doi: 10.3389/fnmol.2023.1266983. eCollection 2023.

Authors

Laura Calvo-Enrique^{1

2}, Silvia Lisa^{1

2}, Cristina Vicente-García^{1

2}, Ruben Deogracias^{1

2}, Juan Carlos Arévalo^{1

2}

Affiliations

¹ Department of Cell Biology and Pathology, Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca, Spain.
² Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.

Abstract

Basal forebrain cholinergic neurons (BFCNs) modulate cognitive functions such as attention, learning and memory. The NGF/TrkA pathway plays an important role in the development and function of BFCNs, although two mouse models conditionally deleting TrkA expression in the central nervous system (CNS) have shown contradictory results. To shed light into this discrepancy, we used a mouse model with a gain-of-function in TrkA receptor signaling. Our results indicate that enhanced TrkA signaling did not alter hippocampal cholinergic innervation, general locomotion or anxiety-related behaviors, but it increases ChAT expression, the number of cholinergic neurons at early postnatal stages and, mutant mice showed impaired motor learning and memory functions. These data demonstrate that proper functioning of the cholinergic system in CNS requires a balanced NGF/TrkA signaling.

Keywords: NGF (nerve growth factor); TrkA; basal forebrain; cholinergic neurons; learning; mice behavior.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by MINECO and MCIN grants (BFU2014-51846-R, BFU2017-82667-R, and PID2020-113130RB-100) and by the EU 7th Framework Program (PAINCAGE) to JCA. LC-E was funded with a postdoctoral contract from Junta Castilla y León (SA0252P20) and from H2020-MSCA-COFUND-2020 (USAL4EXCELLENCE-PROOPI-402) and a Ramón and Cajal grant (RYC2021-034520-I).