Distinct prelimbic cortex ensembles encode response execution and inhibition.

Learning when to initiate or withhold actions is essential for survival, requiring the integration of past experiences with new information to adapt to changing environments. The prelimbic cortex (PL) plays a central role in this process, with a stable PL neuronal population (ensemble) recruited during operant reward learning to encode response execution. However, it is unknown how this established reward-learning ensemble adapts to changing reward contingencies, such as reward omission during extinction.

Using miniscopes and deep learning to compare neurobehavioral representations of psychostimulant and opioid self-administration.

Concurrent abuse of psychostimulants and opioids represents a growing public health concern. However, preclinical models of substance use disorder often situate psychostimulants and opioids similarly within a unified self-administration procedure. This approach may fail to capture important differences in neurobehavioral activity related to each drug type.

Protocol for recording neuronal activity in food and cocaine self-administration in freely behaving mice using calcium imaging.

In vivo calcium imaging has revealed complex neural activity during operant conditioning. Here, we present a protocol for large-scale, long-term recording of neural activity in freely behaving mice using viral injection, gradient lens implantation, and miniscope imaging during food and cocaine administration. We describe daily administration guidelines for comparing food- and cocaine-seeking behaviors.

Cell-type specific epigenetic and transcriptional mechanisms in substance use disorder.

Substance use disorder (SUD) is a chronic and relapse-prone neuropsychiatric disease characterized by impaired brain circuitry within multiple cell types and neural circuits. Recent advancements in single-cell transcriptomics, epigenetics, and neural circuit research have unveiled molecular and cellular alterations associated with SUD. These studies have provided valuable insights into the transcriptional and epigenetic regulation of neuronal and non-neuronal cells, particularly in the context of drug exposure.

Patchy Striatonigral Neurons Modulate Locomotor Vigor in Response to Environmental Valence.

Spiny projection neurons (SPNs) in the dorsal striatum play crucial roles in locomotion control and value-based decision-making. SPNs, which include both direct-pathway striatonigral and indirect-pathway striatopallidal neurons, can be further classified into subtypes based on distinct transcriptomic profiles and cell body distribution patterns. However, how these SPN subtypes regulate spontaneous locomotion in the context of environmental valence remains unclear.

Distinct prelimbic cortex ensembles encode response execution and inhibition.

Learning when to initiate or withhold actions is essential for survival and requires integration of past experiences with new information to adapt to changing environments. While stable prelimbic cortex (PL) ensembles have been identified during reward learning, it remains unclear how they adapt when contingencies shift. Does the same ensemble adjust its activity to support behavioral suppression upon reward omission, or is a distinct ensemble recruited for this new learning? We used single-cell calcium imaging to longitudinally track PL neurons in rats across operant food reward Training, Extinction and Reinstatement, trained rat-specific decoders to predict trial-wise behavior, and implemented an deletion approach to characterize ensemble contributions to behavior.

Miniscope Imaging of Nucleus Accumbens Neural Activity in Freely Behaving Rats: Virus Injection, Gradient Index Lens Implantation, Recording Strategies, and Analytical Methods.

In vivo calcium imaging in freely moving rats using miniscopes provides valuable information about the neural mechanisms of behavior in real time. A gradient index (GRIN) lens can be implanted in deep brain structures to relay activity from single neurons. While such procedures have been successful in mice, few reports provide detailed procedures for successful surgery and long-term imaging in rats, which are better suited for studying complex human behaviors.

Imaging distinct neuronal populations with a dual channel miniscope.

Miniature fluorescence microscopes (miniscopes) are one of the most powerful and versatile tools for recording large scale neural activity in freely moving rodents with single cell resolution. Recent advances in the design of genetically encoded calcium indicators (GECIs) allow to target distinct neuronal populations with non-overlapping emission spectral profiles. However, conventional miniscopes are limited to a single excitation, single focal plane imaging, which does not allow to compensate for chromatic aberration and image from two spectrally distinct calcium indicators.

Individual differences in prelimbic neural representation of food and cocaine seeking.

The prelimbic cortex is involved in operant reward seeking. However, the precise nature of its activity patterns and whether/how they differ between different types of rewards are largely unknown. We use miniscope calcium imaging to observe prelimbic activity during both food and cocaine seeking in freely behaving mice.

Minibox: Custom solo or semi-group housing chambers for long term housing of rats with miniscopes.

In this detailed procedure, we include open-source methodologies using 'solidworks' designs for creating solo or semi-group housing units for rats wearing miniscopes for long periods of time. Builds are optimized to preserve rat health and prevent hardware destruction. We include all prices and suggestions for purchasing strategies to reduce overall build-costs.

Examining a punishment-related brain circuit with miniature fluorescence microscopes and deep learning.

In humans experiencing substance use disorder (SUD), abstinence from drug use is often motivated by a desire to avoid some undesirable consequence of further use: health effects, legal ramifications, etc. This process can be experimentally modeled in rodents by training and subsequently punishing an operant response in a context-induced reinstatement procedure. Understanding the biobehavioral mechanisms underlying punishment learning is critical to understanding both abstinence and relapse in individuals with SUD.

Jump-GRS: a multi-phase approach to structured pruning of neural networks for neural decoding.

Neural decoding, an important area of neural engineering, helps to link neural activity to behavior. Deep neural networks (DNNs), which are becoming increasingly popular in many application fields of machine learning, show promising performance in neural decoding compared to traditional neural decoding methods. Various neural decoding applications, such as brain computer interface applications, require both high decoding accuracy and real-time decoding speed.

GRIN lens applications for studying neurobiology of substance use disorder.

Substance use disorder (SUD) is associated with severe health and social consequences. Continued drug use results in alterations of circuits within the mesolimbic dopamine system. It is critical to observe longitudinal impacts of SUD on neural activity to identify SUD predispositions, develop pharmaceuticals to prevent overdose, and help people suffering from SUD.

Using deep learning to study emotional behavior in rodent models.

Quantifying emotional aspects of animal behavior (e.g., anxiety, social interactions, reward, and stress responses) is a major focus of neuroscience research.

A miniature fluorescence microscope for multi-plane imaging.

Miniature fluorescence microscopes are becoming an increasingly established tool to investigate neural circuits in freely moving animals. In this work we present a lightweight one-photon microscope capable of imaging at different focal depths. The focal plane can be changed dynamically by modulating the pulse width of the control signal to a variable focus liquid lens, which is synchronized to the image sensor to enable changing focal plane between frames.

Dysbindin-1, BDNF, and GABAergic Transmission in Schizophrenia.

Schizophrenia is a psychiatric disorder characterized by hallucinations, anhedonia, disordered thinking, and cognitive impairments. Both genetic and environmental factors contribute to schizophrenia. Dysbindin-1 () and brain-derived neurotrophic factor () are both genetic factors associated with schizophrenia.

Aberrant neural activity in prefrontal pyramidal neurons lacking TDP-43 precedes neuron loss.

Mislocalization of TAR DNA binding protein 43 kDa (TARDBP, or TDP-43) is a principal pathological hallmark identified in cases of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As an RNA binding protein, TDP-43 serves in the nuclear compartment to repress non-conserved cryptic exons to ensure the normal transcriptome. Multiple lines of evidence from animal models and human studies support the view that loss of TDP-43 leads to neuron loss, independent of its cytosolic aggregation.

Striatal direct pathway neurons play leading roles in accelerating rotarod motor skill learning.

Dorsal striatum is important for movement control and motor skill learning. However, it remains unclear how the spatially and temporally distributed striatal medium spiny neuron (MSN) activity in the direct and indirect pathways (D1 and D2 MSNs, respectively) encodes motor skill learning. Combining miniature fluorescence microscopy with an accelerating rotarod procedure, we identified two distinct MSN subpopulations involved in accelerating rotarod learning.

LEARNING COMPACT DNN MODELS FOR BEHAVIOR PREDICTION FROM NEURAL ACTIVITY OF CALCIUM IMAGING.

In this paper, we develop methods for efficient and accurate information extraction from calcium-imaging-based neural signals. The particular form of information extraction we investigate involves predicting behavior variables linked to animals from which the calcium imaging signals are acquired. More specifically, we develop algorithms to systematically generate compact deep neural network (DNN) models for accurate and efficient calcium-imaging-based predictive modeling.

Detailed mapping of behavior reveals the formation of prelimbic neural ensembles across operant learning.

The prelimbic cortex (PrL) is involved in the organization of operant behaviors, but the relationship between longitudinal PrL neural activity and operant learning and performance is unknown. Here, we developed deep behavior mapping (DBM) to identify behavioral microstates in video recordings. We combined DBM with longitudinal calcium imaging to quantify behavioral tuning in PrL neurons as mice learned an operant task.

Anterograde transneuronal tracing and genetic control with engineered yellow fever vaccine YFV-17D.

Transneuronal viruses are powerful tools for tracing neuronal circuits or delivering genes to specific neurons in the brain. While there are multiple retrograde viruses, few anterograde viruses are available. Further, available anterograde viruses often have limitations such as retrograde transport, high neuronal toxicity or weak signals.

Circuit Investigation of Social Interaction and Substance Use Disorder Using Miniscopes.

Substance use disorder (SUD) is comorbid with devastating health issues, social withdrawal, and isolation. Successful clinical treatments for SUD have used social interventions. Neurons can encode drug cues, and drug cues can trigger relapse.

Neural Decoding on Imbalanced Calcium Imaging Data with a Network of Support Vector Machines.

We present a novel neural decoding system for calcium imaging data. Miniature calcium imaging is of great utility for examining population neural activity of animals. Our neural decoding system is developed using a carefully-designed support vector machine subsystem together with dataflow-based techniques for system design, which capture the high-level structure of the application and enable powerful system-level analysis and optimization.