Disorders of the Nervous System
Author: Camila Coll | email: collcami@gmail.com
Camila Coll 1°, Ettel Keifman 1°, Cecilia Tubert 1°, Rodrigo M. Paz 1°, Juan E. Belforte 1°, M. Gustavo Murer 1°, Bárbara Y. Braz 1°
1° Grupo de Neurociencias de Sistemas, Instituto de Fiosiología y Biofísica (IFIBIO) Bernardo Houssay; UBA-CONICET
In Parkinsons Disease patients and rodent models, dopaminergic neuron loss (DAN) results in severe motor disabilities. In contrast, general motility is preserved after early postnatal DAN loss in rodents. In animals rendered parkinsonian by lesioning midbrain dopaminergic neurons during adulthood, medium spiny neurons (MSN) of the dorsomedial striatum (DMS) that belong to the direct pathway (dMSN) are markedly hypoactive and optogenetic activation of DMS-dMSN rescues locomotor activity. Previously we showed that dMSN are hyperexcitable and fully responsive to cortical input in neonatally lesioned mice. Therefore, we asked if preserved locomotion in these animals depends on dMSN activity tone. With this aim, we performed a chemogenetic inhibition of DMS-dMSN in lesioned animals and their control littermates, and we analyzed its effect on locomotion. We found that chemogenetic inhibition of DMS-dMSN has a more marked inhibitory effect on general motility in lesioned mice than in their controls, indicating that expression of normal levels of locomotion and general motility depend on dMSN activity after early DAN loss. Contrastingly, DMS-dMSN inhibition did not ameliorate a characteristic phenotype of the DAN lesioned animals in a marble burying task demanding higher behavioral control. Thus, increased dMSN excitability likely promoting changes in corticostriatal functional connectivity may contribute to the distinctive behavioral phenotype emerging after developmental DAN loss.