Maturation of cortical input to dorsal raphe nucleus increases behavioral persistence in mice.
Nicolas Gutierrez-CastellanosDario SarraBeatriz S GodinhoZachary F MainenPublished in: eLife (2024)
The ability to persist toward a desired objective is a fundamental aspect of behavioral control whose impairment is implicated in several behavioral disorders. One of the prominent features of behavioral persistence is that its maturation occurs relatively late in development. This is presumed to echo the developmental time course of a corresponding circuit within late-maturing parts of the brain, such as the prefrontal cortex, but the specific identity of the responsible circuits is unknown. Here, we used a genetic approach to describe the maturation of the projection from layer 5 neurons of the neocortex to the dorsal raphe nucleus in mice. Using optogenetic-assisted circuit mapping, we show that this projection undergoes a dramatic increase in synaptic potency between postnatal weeks 3 and 8, corresponding to the transition from juvenile to adult. We then show that this period corresponds to an increase in the behavioral persistence that mice exhibit in a foraging task. Finally, we used a genetic targeting strategy that primarily affected neurons in the medial prefrontal cortex, to selectively ablate this pathway in adulthood and show that mice revert to a behavioral phenotype similar to juveniles. These results suggest that frontal cortical to dorsal raphe input is a critical anatomical and functional substrate of the development and manifestation of behavioral persistence.
Keyphrases
- prefrontal cortex
- spinal cord
- high fat diet induced
- neuropathic pain
- magnetic resonance
- metabolic syndrome
- magnetic resonance imaging
- type diabetes
- adipose tissue
- high resolution
- genome wide
- young adults
- resting state
- skeletal muscle
- insulin resistance
- depressive symptoms
- functional connectivity
- cancer therapy
- white matter
- diffusion weighted
- amino acid
- cerebral ischemia
- childhood cancer