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Pierce, A. F.

Publications and source records attributed to Pierce, A. F..

5 recordsLinked to original sources

Flexible modeling of large-scale neural network stimulation: electrical and optical extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX)

BackgroundComputational models that predict effects of neural stimulation can be used as a preliminary tool to inform in-vivo research, reducing the costs, time, and ethical considerations involved. However, current models do not support the diverse neural stimulation techniques used in-vivo, including the expanding selection of electrodes, stimulation modalities, and stimulation paradigms. New MethodTo develop a more comprehensive software, we created several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool from Newcastle University. VERTEX simulates input currents in a large population of multi-compartment neurons within a small cortical slice to model electric field stimulation, while recording local field potentials (LFPs) and spiking activity. Our extensions to its existing electric field stimulation framework include allowing multiple pairs of parametrically defined electrodes and biphasic, bipolar stimulation delivered at programmable delays. To support the growing use of optogenetic approaches for targeted neural stimulation, we introduced a feature that models optogenetic stimulation through an additional VERTEX input function that converts irradiance to currents at optogenetically responsive neurons. Finally, we added extensions to allow complex stimulation protocols including paired-pulse, spatiotemporal patterned, and closed-loop stimulation. ResultsWe demonstrated our novel features using VERTEXs built-in functionalities, with results in alignment with other models and experimental work. ConclusionsOur extensions provide an all in one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.

neuroscience↗

PhAT: A flexible open-source GUI-driven toolkit for photometry analysis

Photometry approaches detect sensor-mediated changes in fluorescence as a proxy for rapid molecular changes within the brain. As a flexible technique with a relatively low cost to implement, photometry is rapidly being incorporated into neuroscience laboratories. While multiple data acquisition systems for photometry now exist, robust analytical pipelines for the resulting data remain limited. Here we present the Photometry Analysis Toolkit (PhAT) - a free open source analysis pipeline that provides options for signal normalization, incorporation of multiple data streams to align photometry data with behavior and other events, calculation of event-related changes in fluorescence, and comparison of similarity across fluorescent traces. A graphical user interface (GUI) enables use of this software without prior coding knowledge. In addition to providing foundational analytical tools, PhAT is designed to readily incorporate community-driven development of new modules for more bespoke analyses, and data can be easily exported to enable subsequent statistical testing and/or code-based analyses. In addition, we provide recommendations regarding technical aspects of photometry experiments including sensor selection and validation, reference signal considerations, and best practices for experimental design and data collection. We hope that the distribution of this software and protocol will lower the barrier to entry for new photometry users and improve the quality of collected data, increasing transparency and reproducibility in photometry analyses. Basic Protocol 1: Software Environment Installation Basic Protocol 2: GUI-driven Fiber Photometry Analysis Basic Protocol 3: Adding Modules

neuroscience↗

Nucleus accumbens dopamine release reflects the selective nature of pair bonds

In monogamous species, prosocial behaviors directed towards partners are dramatically different from those directed towards unknown individuals and potential threats. Dopamine release in the nucleus accumbens plays an important role in guiding social behavior, however, its role in real time social decision making in a monogamous species remains largely unknown. We used monogamous prairie voles to investigate how dopamine release differs in voles when seeking and interacting with a pair bonded partner or a novel vole. Employing the sub-second temporal resolution of the fluorescent biosensor, GRABDA, during a social operant task, we found that partner seeking, anticipation, and interaction resulted in more dopamine release than the same events directed towards a novel vole. Furthermore, partner-elicited dopamine release decreases after prolonged partner separation. Thus, differences in partner- and novel-elicited dopamine release reflect the selective nature of pair bonds and may drive the social behaviors that reinforce and cement bonds over time, eroding after partner loss to facilitate new bond formation.

neuroscience↗

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

How does the prefrontal cortex (PFC) regulate motivated behavior? Our experiments characterize the circuits of the PFC regulating motivation, reinforcement and dopamine activity, revealing a novel cortico-thalamic loop. The stimulation of medial PFC (mPFC) neurons activated many downstream regions, as shown by functional MRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. Reciprocal excitatory functional connectivity, as well as co-activation of the two regions, was found in human participants who watched reinforcing videos. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement and dopaminergic neuron activity.

neuroscience↗

Insular Cortex Mediates Approach And Avoidance Responses To Social Affective Stimuli

Social animals detect the affective states of others and utilize this information to orchestrate appropriate social interactions. Social affective behaviors include cooperation, reproductive acts and avoiding sick individuals. In a social affective behavioral test in which experimental adult male rats were given the choice to interact with either naive or stressed conspecifics, the experimental rats demonstrated both approach and avoidant behaviors towards the conspecific, depending upon the age of the conspecific; experimental adult rats approached the stressed juvenile but avoided the stressed adult. Optogenetic inhibition of the insular cortex, a region anatomically positioned to contribute to social cognition, disrupted these behaviors. Receptors for the social nonapeptide oxytocin (OT) are found in high density within the insular cortex and here oxytocin increased intrinsic excitability and synaptic efficacy in acute insular cortex slices. Blockade of oxytocin receptors (OTRs) in the insula eliminated the effect of conspecific stress on approach behavior, while insular administration of OT recapitulated the behaviors typically observed in response to stressed conspecifics. Network analysis using Fos immunoreactivity identified functional connectivity between the insular cortex and the network of regions involved in social decision making. These results implicate insular cortex as a novel target of OT and suggest that insula is a key component in the circuit underlying age-dependent social responses to stressed conspecifics.

neuroscience↗