Many molecules expressed in the CNS contribute to cognitive functions either by modulating neuronal activity or by mediating neuronal trophic support and/or connectivity. An ongoing discussion is whether signaling of nerve growth factor (NGF) through its high-affinity receptor Trk A contributes to attention behavior and/or learning and memory, based on its expression in relevant regions of the CNS such as the hippocampus, cerebral cortex, amygdala and basal forebrain. Previous animal models carrying either a null allele or transgenic manipulation of Ng for Trk a have proved difficult in addressing this question. To overcome this problem, we conditionally deleted Ngf or Trk a from the CNS. Our findings confirm that NGF-Trk A signaling supports survival of only a small proportion of cholinergic neurons during development; however, this signaling is not required for trophic support or connectivity of the remaining basal forebrain cholinergic neurons. Moreover, comprehensive behavioral analysis of young adult and intermediate-aged mice lacking NGF-TrkA signaling demonstrates that this signaling is dispensable for both attention behavior and various aspects of learning and memory.

Loss of NGF-TrkA signaling from the CNS is not sufficient to induce cognitive impairments in young adult or intermediate-aged mice / M. Muller, V. Triaca, D. Besusso, M. Costanzi, J.M. Horn, J. Koudelka, M. Geibel, V. Cestari, L. Minichiello. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 32:43(2012), pp. 14885-14898. [10.1523/JNEUROSCI.2849-12.2012]

Loss of NGF-TrkA signaling from the CNS is not sufficient to induce cognitive impairments in young adult or intermediate-aged mice

D. Besusso;
2012

Abstract

Many molecules expressed in the CNS contribute to cognitive functions either by modulating neuronal activity or by mediating neuronal trophic support and/or connectivity. An ongoing discussion is whether signaling of nerve growth factor (NGF) through its high-affinity receptor Trk A contributes to attention behavior and/or learning and memory, based on its expression in relevant regions of the CNS such as the hippocampus, cerebral cortex, amygdala and basal forebrain. Previous animal models carrying either a null allele or transgenic manipulation of Ng for Trk a have proved difficult in addressing this question. To overcome this problem, we conditionally deleted Ngf or Trk a from the CNS. Our findings confirm that NGF-Trk A signaling supports survival of only a small proportion of cholinergic neurons during development; however, this signaling is not required for trophic support or connectivity of the remaining basal forebrain cholinergic neurons. Moreover, comprehensive behavioral analysis of young adult and intermediate-aged mice lacking NGF-TrkA signaling demonstrates that this signaling is dispensable for both attention behavior and various aspects of learning and memory.
Analysis of Variance; Animals; Attention; Avoidance Learning; Cell Count; Central Nervous System; Choice Behavior; Choline O-Acetyltransferase; Cholinergic Neurons; Cognition Disorders; Conditioning, Psychological; Cues; Disease Models, Animal; Exploratory Behavior; Fear; In Situ Nick-End Labeling; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Growth Factor; Receptor, trkA; Receptors, Nerve Growth Factor; Signal Transduction; Aging
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/794557
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