Neural Circuits and Systems Neuroscience
Author: Matias Ezequiel Cure | Email: matiascure3@gmail.com
Matias Ezequiel Cure1°, Paula Ravettino1°, Daniela Cassano1°, Ivana María Gomez1°, Mirta Reynaldo1°, María José Tolosa1°, Mario Perello1°, Pablo Nicolás De Francesco1°, Gimena Fernandez1°
1° Laboratorio de Neurofisiología del Instituto Multidisciplinario de Biología Celular (CONICET, UNLP, CIC-PBA), 1900 La Plata, Buenos Aires, Argentina.
Agouti Related Protein-expressing neurons of the Hypothalamic Arcuate Nucleus (ARHAgRP) constitute a key population involved in food intake regulation and energy balance. These neurons drive strong orexigenic responses and are activated under energetic deficit conditions, such as fasting. We hypothesize that an increased activity of ARHAgRP neurons during fasting promotes remodeling of AgRP projections to their target nuclei, which could in turn modulate their efferent response profile. We used a transgenic mouse model expressing tdTomato in AgRP neurons (Agrp-cre×Rosa26-tdTom, named Agrp-Tom) along with immunofluorescence to explore this system. We first validated the model by performing AgRP staining in colchicine-treated Agrp-Tom mice and evaluated both fluorescent signals in ARH neurons, which showed a high degree of colocalization. Then, we studied both signals in the ARH of fasted mice and found an increase in AgRP+ signal without changes in tdTom fluorescence. We also observed the activation of tdTom+ neurons with fasting by c-Fos staining. Finally, we studied the distribution and colocalization of both signals in fibers innervating several intra- and extrahypothalamic target nuclei, and their modulation by fasting. We found evidence of differential modulation of ARHAgRP fiber density with fasting in some, but not all, of the studied nuclei. Overall, our results indicate that fasting modifies the efferent connectivity of ARHAgRP neurons in a target-dependent manner.