Cannabinoid mitigation of neuronal morphological change important to development and learning: Insight from a zebra finch model of psychopharmacology

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory.

A. Juvenile males memorize the song of an adult tutor during the auditory learning stage of vocal development. B. This learning is associated with rapid changes in dendritic spine dynamics (Roberts et al., 2010). C. Sensorimotor practice of previously-memorized song depends on auditory perception, results in gradual refinement of song produced during adolescence and is associated with decreased dendritic spine densities in some brain areas by adulthood. D. Daily cannabinoid exposure disrupts vocal learning (Soderstrom and Johnson, 2003) and results in inappropriately-elevated dendritic spine densities in adulthood (Gilbert and Soderstrom, 2011). E. Exposure of adults to a novel song results in upregulation of ZENK (reviewed by Mello et al., 2004), Arc/Arg3.1 (Velho et al., 2005) and Caspase-3 (Huesmann and Clayton, 2006). F. Cannabinoid agonist treatment prior to novel song exposure prevents upregulation and activation (Whitney, et al., 2003, Figs. 3 and 4). G and H. Cannabinoid pretreatment prevents acute upregulation of dendritic spine densities (Gilbert and Soderstrom, submitted).Figure optionsDownload high-quality image (286 K)Download as PowerPoint slide