A Systematic Review of the Effects of Perinatal Alcohol Exposure and Perinatal Marijuana Exposure on Adult Neurogenesis in the Dentate Gyrus.

BACKGROUND: Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis. METHODS: This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized. RESULTS: Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus. CONCLUSIONS: Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus.

Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex.

BACKGROUND: Both psychostimulant use and engagement with probabilistic schedules of reward sensitize the mesocorticolimbic dopamine (DA) system. Such behaviors may act synergistically to explain the high comorbidity between stimulant use and gambling disorder. The salient audiovisual stimuli of modern electronic gambling may exacerbate the situation. METHODS: To probe these interactions, we sensitized ventral tegmental area DA neurons via chronic chemogenetic stimulation while rats (n = 134) learned a rat gambling task in the presence or absence of casino-like cues. The same rats then learned to self-administer cocaine. In a separate cohort (n = 25), we confirmed that our chemogenetic methods sensitized the locomotor response to cocaine and potentiated phasic excitability of ventral tegmental area DA neurons through in vivo electrophysiological recordings. RESULTS: In the absence of cues, sensitization promoted risk taking in both sexes. When rewards were cued, sensitization expedited the development of a risk-preferring phenotype in males while attenuating cue-induced risk taking in females. CONCLUSIONS: While these results provide further confirmation that ventral tegmental area DA neurons critically modulate risky decision making, they also reveal stark sex differences in the decisional impact that dopaminergic signals exert when winning outcomes are cued. As previously observed, risky decision making on the cued rat gambling task increased as both males and females learned to self-administer cocaine. The combination of DA sensitization and win-paired cues while gambling led to significantly greater cocaine taking, but these rats did not show any increase in risky choice as a result. Therefore, cocaine and heavily cued gambles may partially substitute for each other once the DA system has been rendered labile through sensitization, thereby compounding addiction risk across modalities.

Multiple Object Tracking Scores Predict Post-Concussion Status Years after Mild Traumatic Brain Injury.

The diagnosis of concussion remains challenging, particularly in cases where several months have passed between a traumatic brain injury (TBI) and clinical assessment. Tracking multiple moving objects in three-dimensional (3D) space engages many of the same cognitive processes that are affected by concussion, a form of mild TBI (mTBI), suggesting that tests of 3D multiple object tracking (3D-MOT) may be sensitive to post-concussion syndrome (PCS) after a brain injury has occurred. To test this, we evaluated 3D-MOT performance (using NeuroTrackerTM) against Sports Concussion Assessment Tool results for cognition, balance, and symptom severity in a large sample (N = 457) of male and female participants between the ages of 6 and 73 years. 3D-MOT performance in subjects under age 13 was not impaired by a history of concussion, but was positively associated with cognition and balance. 3D-MOT performance in those 13 and older was negatively associated with concussion symptom severity and positively associated with cognition and balance. 3D-MOT was selectively impaired in subjects with probable PCS (pPCS), defined using the 95th percentile of symptom severity for subjects with no history of concussion. A decision tree predicted concussion status with 95.2% overall test accuracy (91.1% sensitivity, 97.8% specificity), using concussion history, age, and 3D-MOT score. Persons with a history of concussion in the past 37 days were predicted to have pPCS if they were ≥35 years of age, or if they were <35 years of age but achieved scores below 1.2 on the 3D-MOT. These results demonstrate the potential of 3D-MOT for pPCS diagnosis and highlight the increased vulnerability to concussion symptoms that comes with age.