Molecular Features Underlying Neurodegeneration Identified through In Vitro Modeling of Genetically Diverse Parkinson's Disease Patients.

The fact that Parkinson's disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, we generated neurons harboring disease-causing mutations from patient-specific, induced pluripotent stem cells (iPSCs).

Stimulus information stored in lasting active and hidden network states is destroyed by network bursts.

In both humans and animals brief synchronizing bursts of epileptiform activity known as interictal epileptiform discharges (IEDs) can, even in the absence of overt seizures, cause transient cognitive impairments (TCI) that include problems with perception or short-term memory. While no evidence from single units is available, it has been assumed that IEDs destroy information represented in neuronal networks. Cultured neuronal networks are a model for generic cortical microcircuits, and their spontaneous activity is characterized by the presence of synchronized network bursts (SNBs), which share a number of properties with IEDs, including the high degree of synchronization and their spontaneous occurrence in the absence of an external stimulus.

Spatiotemporal memory is an intrinsic property of networks of dissociated cortical neurons.

The ability to process complex spatiotemporal information is a fundamental process underlying the behavior of all higher organisms. However, how the brain processes information in the temporal domain remains incompletely understood. We have explored the spatiotemporal information-processing capability of networks formed from dissociated rat E18 cortical neurons growing in culture.

Short-term memory in networks of dissociated cortical neurons.

Short-term memory refers to the ability to store small amounts of stimulus-specific information for a short period of time. It is supported by both fading and hidden memory processes. Fading memory relies on recurrent activity patterns in a neuronal network, whereas hidden memory is encoded using synaptic mechanisms, such as facilitation, which persist even when neurons fall silent.

Neural dynamics underlying impaired autonomic and conditioned responses following amygdala and orbitofrontal lesions.

A neural model is presented that explains how outcome-specific learning modulates affect, decision-making, and Pavlovian conditioned approach responses. The model addresses how brain regions responsible for affective learning and habit learning interact and answers a central question: What are the relative contributions of the amygdala and orbitofrontal cortex to emotion and behavior? In the model, the amygdala calculates outcome value while the orbitofrontal cortex influences attention and conditioned responding by assigning value information to stimuli. Model simulations replicate autonomic, electrophysiological, and behavioral data associated with three tasks commonly used to assay these phenomena: Food consumption, Pavlovian conditioning, and visual discrimination.

Dopaminergic and non-dopaminergic value systems in conditioning and outcome-specific revaluation.

Animals are motivated to choose environmental options that can best satisfy current needs. To explain such choices, this paper introduces the MOTIVATOR (Matching Objects To Internal VAlues Triggers Option Revaluations) neural model. MOTIVATOR describes cognitive-emotional interactions between higher-order sensory cortices and an evaluative neuraxis composed of the hypothalamus, amygdala, and orbitofrontal cortex.