Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice.

Astronauts will encounter extended exposure to galactic cosmic radiation (GCR) during deep space exploration, which could impair brain function. Here, we report that in male mice, acute or chronic GCR exposure did not modify reward sensitivity but did adversely affect attentional processes and increased reaction times. Potassium (K+)-stimulation in the prefrontal cortex (PFC) elevated dopamine (DA) but abolished temporal DA responsiveness after acute and chronic GCR exposure.

Validation of a touchscreen probabilistic reward task for mice: A reverse-translated assay with cross-species continuity.

The Probabilistic Reward Task (PRT) is a laboratory-based technique used to objectively quantify responsivity to reward. The PRT was initially designed to identify reinforcement learning deficits in clinical populations and subsequently was reverse-translated for use in preclinical studies with rats and monkeys. In this task, subjects make visual discriminations and asymmetric probabilistic contingencies are arranged such that correct responses to one stimulus (rich) are reinforced more often than correct responses to the other (lean).

Electrophysiological signatures of reward learning in the rodent touchscreen-based Probabilistic Reward Task.

Blunted reward learning and reward-related activation within the corticostriatal-midbrain circuitry have been implicated in the pathophysiology of anhedonia and depression. Unfortunately, the search for more efficacious interventions for anhedonic behaviors has been hampered by the use of vastly different preclinical and clinical assays. In a first step in addressing this gap, in the current study, we used event-related potentials and spectral analyses in conjunction with a touchscreen version of the rodent Probabilistic Reward Task (PRT) to identify the electrophysiological signatures of reward learning in rats.

Toward a Quantification of Anhedonia: Unified Matching Law and Signal Detection for Clinical Assessment and Drug Development.

Anhedonia, the loss of pleasure from previously rewarding activities, is a core symptom of several neuropsychiatric conditions, including major depressive disorder (MDD). Despite its transdiagnostic relevance, no effective therapeutics exist to treat anhedonia. This is due, in part, to inconsistent assays across clinical populations and laboratory animals, which hamper treatment development.

A cross-species assay demonstrates that reward responsiveness is enduringly impacted by adverse, unpredictable early-life experiences.

Exposure to early-life adversity (ELA) is associated with several neuropsychiatric conditions, including major depressive disorder, yet causality is difficult to establish in humans. Recent work in rodents has implicated impaired reward circuit signaling in anhedonic-like behavior after ELA exposure. Anhedonia, the lack of reactivity to previously rewarding stimuli, is a transdiagnostic construct common to mental illnesses associated with ELA.

Concurrent electrophysiological recording and cognitive testing in a rodent touchscreen environment.

Challenges in therapeutics development for neuropsychiatric disorders can be attributed, in part, to a paucity of translational models capable of capturing relevant phenotypes across clinical populations and laboratory animals. Touch-sensitive procedures are increasingly used to develop innovative animal models that better align with testing conditions used in human participants. In addition, advances in electrophysiological techniques have identified neurophysiological signatures associated with characteristics of neuropsychiatric illness.

Empirical validation of a touchscreen probabilistic reward task in rats.

Anhedonia, the loss of pleasure from previously rewarding activities, is implicated in several neuropsychiatric conditions, including major depressive disorder (MDD). In order to accelerate drug development for mood disorders, quantitative approaches are needed to objectively measure responsiveness to reward as a means to identify deficits. One such approach, the probabilistic reward task (PRT), uses visual discrimination methodology to quantify reward learning.