Optogenetic Stimulation of the Basolateral Amygdala Increased Theta-Modulated Gamma Oscillations in the Hippocampus.

The amygdala can modulate declarative memory. For example, previous research in rats and humans showed that brief electrical stimulation to the basolateral complex of the amygdala (BLA) prioritized specific objects to be consolidated into long term memory in the absence of emotional stimuli and without awareness of stimulation. The capacity of the BLA to influence memory depends on its substantial projections to many other brain regions, including the hippocampus. Nevertheless, how activation of the BLA influences ongoing neuronal activity in other regions is poorly understood. The current study used optogenetic stimulation of putative glutamatergic neurons in the BLA of freely exploring rats to determine whether brief activation of the BLA could increase in the hippocampus gamma oscillations for which the amplitude was modulated by the phase of theta oscillations, an oscillatory state previously reported to correlate with good memory. BLA neurons were stimulated in 1-s bouts with pulse frequencies that included the theta range (8 Hz), the gamma range (50 Hz), or a combination of both ranges (eight 50-Hz bursts). Local field potentials were recorded in the BLA and in the pyramidal layer of CA1 in the intermediate hippocampus. A key question was whether BLA stimulation at either theta or gamma frequencies could combine with ongoing hippocampal oscillations to result in theta-modulated gamma or whether BLA stimulation that included both theta and gamma frequencies would be necessary to increase theta-gamma comodulation in the hippocampus. All stimulation conditions elicited robust responses in BLA and CA1, but theta-modulated gamma oscillations increased in CA1 only when BLA stimulation included both theta and gamma frequencies. Longer bouts (5-s) of BLA stimulation resulted in hippocampal activity that evolved away from the initial oscillatory states and toward those characterized more by prominent low-frequency oscillations. The current results indicated that one mechanism by which the amygdala might influence declarative memory is by eliciting neuronal oscillatory states in the hippocampus that benefit memory.

Prodromes and Preclinical Detection of Brain Diseases: Surveying the Ethical Landscape of Predicting Brain Health.

The future of medicine lies not primarily in cures but in disease modification and prevention. While the science of preclinical detection is young, it is moving rapidly. Preclinical interventions offer hope to decrease the severity of a disease or delay the development of a disorder. With such promise, the research and practice of detecting brain disorders at a preclinical stage present unique ethical challenges that must be addressed to ensure the benefit of these technologies. Direct brain interventions have the potential to impact not just what a patient has but who they are and who they could become. Further, receiving an assessment for a preclinical or prodromal state has potential to impact perceptions about capacity, autonomy and personhood and could become entangled with stigma and discrimination. Exploring ethical issues alongside and integrated into the experimental design and research of these technologies is critical. This review will highlight ethical issues attendant to the current and near future states of preclinical detection across the life span, specifically as it relates to autism spectrum disorder (ASD), schizophrenia, and Alzheimer's disease.

Neonatal perirhinal cortex lesions impair monkeys' ability to modulate their emotional responses.

The medial temporal lobe (MTL) is a collection of brain regions best known for their role in perception, memory, and emotional behavior. Within the MTL, the perirhinal cortex (PRh) plays a critical role in perceptual representation and recognition memory, although its contribution to emotional regulation is still debated. Here, rhesus monkeys with neonatal perirhinal lesions (Neo-PRh) and controls (Neo-C) were tested on the Human Intruder (HI) task at 2 months, 4.5 months, and 5 years of age to assess the role of the PRh in the development of emotional behaviors. The HI task presents a tiered social threat to which typically developing animals modulate their emotional responses according to the level of threat. Unlike animals with neonatal amygdala or hippocampal lesions, Neo-PRh animals were not broadly hyper- or hyporesponsive to the threat presented by the HI task as compared with controls. Instead, Neo-PRh animals displayed an impaired ability to modulate their freezing and anxiety-like behavioral responses according to the varying levels of threat. Impaired transmission of perceptual representation generated by the PRh to the amygdala and hippocampus may explain the animals' inability to appropriately assess and react to complex social stimuli. Neo-PRh animals also displayed fewer hostile behaviors in infancy and more coo vocalizations in adulthood. Neither stress-reactive nor basal cortisol levels were affected by the Neo-PRh lesions. Overall, these results suggest that the PRh is indirectly involved in the expression of emotional behavior and that effects of Neo-PRh lesions are dissociable from neonatal lesions to other temporal lobe structures. (PsycINFO Database Record