Alcohol use disorders are a major public health issue and emerging evidence suggests that high-risk drinking during adolescence has long-term consequences on behavior and brain development. The brain undergoes profound structural and functional adaptations throughout adolescence, and some critical brain regions even continue to mature into early adulthood. Over the last few years, studies published from the NADIA Consortium and other laboratories showed that adolescent intermittent alcohol (AIE) exposure produces profound behavioral, cognitive, electrophysiological, and neuroanatomical impairments that persist in adult rodents. The underlying neuroadaptations that contribute to the persistent consequences of high-risk adolescent drinking remain largely unknown. Three components of the NADIA Consortium found that AIE exposure alters dendritic spine density and morphology in the adult amygdala (Pandey component), prefrontal cortex (Chandler component), and hippocampus (Swartzwelder component). An analysis of the morphological characteristics of spines revealed that AIE exposure selectively increased the prevalence of `immature' long, thin dendritic spines in the adult prefrontal cortex and hippocampus. Previous findings suggest that maturation of asymmetric synapses during the natural process of developmental pruning involves replacing immature synapses associated with long, thin spines with mature synapses associated with mushroom-shaped dendritic spines. Thus, AIE exposure appears to impair the normal maturation of synaptic pruning in the adult brain. Because dendritic spine morphology influences synaptic physiology and behavior, aberrant structural plasticity of neurons in the adult brain is a likely neural mechanism underlying deficits in cognition and behavior associated with AIE exposure. The convergence of these findings prompted the formation of a NADIA Dendritic Spine Core that will integrate dendritic spines changes in multiple brain regions induced by AIE exposure. The overarching hypothesis of this NADIA Dendritic Spine Core is that AIE exposure locks-in an adolescent morphological phenotype in the adult brain that diverges from the normal pruning process. The purpose of this Core is to provide a detailed analysis of dendritic spine density and spine morphology in brain regions relevant to the behavioral, electrophysiological, and epigenetic studies of the NADIA Consortium. The Dendritic Spine Core will provide analysis of dendritic spine changes in a primary and secondary brain region for each NADIA component. This Core will also characterize developmental changes in dendritic spine density and morphology in brain regions related to the NADIA Consortium components. The data provided to the NADIA Consortium by this Core on the impact of AIE exposure on dendritic spine adaptations and the developmental trajectory of spine morphology will influence the neuroscience field and inform public health.
We expect that data collected from these proposed studies will advance our understanding of changes in the adult brain caused by alcohol exposure during adolescence. These studies will also provide evidence for developmental changes in sites of brain cell communication.
| Mulholland, Patrick J; Teppen, Tara L; Miller, Kelsey M et al. (2018) Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure. Alcohol Clin Exp Res 42:706-717 |
