Direct Comparison of Epifluorescence and Immunostaining for Assessing Viral Mediated Gene Expression in the Primate Brain.

Viral vector technologies are commonly used in neuroscience research to understand and manipulate neural circuits, but successful applications of these technologies in non-human primate models have been inconsistent. An essential component to improve these technologies is an impartial and accurate assessment of the effectiveness of different viral constructs in the primate brain. We tested a diverse array of viral vectors delivered to the brain and extraocular muscles of macaques and compared three methods for histological assessment of viral-mediated fluorescent transgene expression: epifluorescence (Epi), immunofluorescence (IF), and immunohistochemistry (IHC). Importantly, IF and IHC identified a greater number of transduced neurons compared to Epi. Furthermore, IF and IHC reliably provided enhanced visualization of transgene in most cellular compartments (i.e., dendritic, axonal, and terminal fields), whereas the degree of labeling provided by Epi was inconsistent and predominantly restricted to somas and apical dendrites. Because Epi signals are unamplified (in contrast to IF and IHC), Epi may provide a more veridical assessment for the amount of accumulated transgene and, thus, the potential to chemogenetically or optogenetically manipulate neuronal activity. The comparatively weak Epi signals suggest that the current generations of viral constructs, regardless of delivered transgene, are not optimized for primates. This reinforces an emerging viewpoint that viral vectors tailored for the primate brain are necessary for basic research and human gene therapy.

Causal role for the primate superior colliculus in the computation of evidence for perceptual decisions.

Trained monkeys performed a two-choice perceptual decision-making task in which they reported the perceived orientation of a dynamic Glass pattern, before and after unilateral, reversible, inactivation of a brainstem area-the superior colliculus (SC)-involved in preparing eye movements. We found that unilateral SC inactivation produced significant decision biases and changes in reaction times consistent with a causal role for the primate SC in perceptual decision-making. Fitting signal detection theory and sequential sampling models to the data showed that SC inactivation produced a decrease in the relative evidence for contralateral decisions, as if adding a constant offset to a time-varying evidence signal for the ipsilateral choice. The results provide causal evidence for an embodied cognition model of perceptual decision-making and provide compelling evidence that the SC of primates (a brainstem structure) plays a causal role in how evidence is computed for decisions-a process usually attributed to the forebrain.

Timescales of Evidence Evaluation for Decision Making and Associated Confidence Judgments Are Adapted to Task Demands.

Decision making often involves choosing actions based on relevant evidence. This can benefit from focussing evidence evaluation on the timescale of greatest relevance based on the situation. Here, we use an auditory change detection task to determine how people adjust their timescale of evidence evaluation depending on task demands for detecting changes in their environment and assessing their internal confidence in those decisions. We confirm previous results that people adopt shorter timescales of evidence evaluation for detecting changes in contexts with shorter signal durations, while bolstering those results with model-free analyses not previously used and extending the results to the auditory domain. We also extend these results to show that in contexts with shorter signal durations, people also adopt correspondingly shorter timescales of evidence evaluation for assessing confidence in their decision about detecting a change. These results provide important insights into adaptability and flexible control of evidence evaluation for decision making.