Behavioral Neuroscience Experiments Research Articles

Pybehave: a hardware agnostic, Python-based framework for controlling behavioral neuroscience experiments

Pybehave: a hardware agnostic, Python-based framework for controlling behavioral neuroscience experiments

Nucleus Accumbens Chemogenetic Inhibition Suppresses Amphetamine-Induced Ultrasonic Vocalizations in Male and Female Rats.

Adult rats emit ultrasonic vocalizations (USVs) related to their affective states, potentially providing information about their subjective experiences during behavioral neuroscience experiments. If so, USVs might provide an important link between invasive animal preclinical studies and human studies in which subjective states can be readily queried. Here, we induced USVs in male and female Long Evans rats using acute amphetamine (2 mg/kg), and asked how reversibly inhibiting nucleus accumbens neurons using designer receptors exclusively activated by designer drugs (DREADDs) impacts USV production. We analyzed USV characteristics using “Deepsqueak” software, and manually categorized detected calls into four previously defined subtypes. We found that systemic administration of the DREADD agonist clozapine-n-oxide, relative to vehicle in the same rats, suppressed the number of frequency-modulated and trill-containing USVs without impacting high frequency, unmodulated (flat) USVs, nor the small number of low-frequency USVs observed. Using chemogenetics, these results thus confirm that nucleus accumbens neurons are essential for production of amphetamine-induced frequency-modulated USVs. They also support the premise of further investigating the characteristics and subcategories of these calls as a window into the subjective effects of neural manipulations, with potential future clinical applications.

Modular Optoelectronic System for Wireless, Programmable Neuromodulation During Free Behavior.

This work presents a modular, light-weight head-borne neuromodulation platform that achieves low-power wireless neuromodulation and allows real-time programmability of the stimulation parameters such as the frequency, duty cycle, and intensity. This platform is comprised of two parts: the main device and the optional intensity module. The main device is functional independently, however, the intensity control module can be introduced on demand. The stimulation is achieved through the use of energy-efficient µLEDs directly integrated in the custom-drawn fiber-based probes. Our platform can control up to 4 devices simultaneously and each device can control multiple LEDs in a given subject. Our hardware uses off-the-shelf components and has a plug and play structure, which allows for fast turn-over time and eliminates the need for complex surgeries. The rechargeable, battery-powered wireless platform uses Bluetooth Low Energy (BLE) and is capable of providing stable power and communication regardless of orientation. This presents a potential advantage over the battery-free, fully implantable systems that rely on wireless power transfer, which is typically direction-dependent, requires sophisticated implantation surgeries, and demands complex custom-built experimental apparatuses. Although the battery life is limited to several hours, this is sufficient to complete the majority of behavioral neuroscience experiments. Our platform consumes an average power of 0.5 mW, has a battery life of 12 hours.

USE: An integrative suite for temporally-precise psychophysical experiments in virtual environments for human, nonhuman, and artificially intelligent agents

BackgroundThere is a growing interest in complex, active, and immersive behavioral neuroscience tasks. However, the development and control of such tasks present unique challenges. New MethodThe Unified Suite for Experiments (USE) is an integrated set of hardware and software tools for the design and control of behavioral neuroscience experiments. The software, developed using the Unity video game engine, supports both active tasks in immersive 3D environments and static 2D tasks used in more traditional visual experiments. The custom USE SyncBox hardware, based around an Arduino Mega2560 board, integrates and synchronizes multiple data streams from different pieces of experimental hardware. The suite addresses three key issues with developing cognitive neuroscience experiments in Unity: tight experimental control, accurate sub-ms timing, and accurate gaze target identification. ResultsUSE is a flexible framework to realize experiments, enabling (i) nested control over complex tasks, (ii) flexible use of 3D or 2D scenes and objects, (iii) touchscreen-, button-, joystick- and gaze-based interaction, and (v) complete offline reconstruction of experiments for post-processing and temporal alignment of data streams. Comparison with Existing MethodsMost existing experiment-creation tools are not designed to support the development of video-game-like tasks. Those that do use older or less popular video game engines as their base, and are not as feature-rich or enable as precise control over timing as USE. ConclusionsUSE provides an integrated, open source framework for a wide variety of active behavioral neuroscience experiments using human and nonhuman participants, and artificially-intelligent agents.

Empathy as a Concept from Bench to Bedside: A Translational Challenge.

Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus in its definition. In this paper, we review the possibility of compromising data during behavioral neuroscience experiments, including but not limited to those who study empathy. The experimental protocols can affect, and be affected by, empathy and related processes at multiple levels. We discuss several points to help researchers develop a successful translational pathway for behavioral research on empathy. Despite varying in their focus with no widely accepted model, current rodent models on empathy have provided sound translational explanations for many neuropsychiatric proof-of-concepts to date. Research has shown that empathy can be influenced by many parameters, some of which are to be reviewed in this paper. We emphasize the future importance of consistency in modeling proof of concept; efforts to create a multidisciplinary group which would include both bench scientists and clinicians with expertise in neuropsychiatry, and the consideration of empathy as an independent variable in animal behavioral experimental designs which is not the mainstream practice at present.

Voluntary Control of Epileptiform Spike-Wave Discharges in Awake Rats.

Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike-wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities, and antiabsence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats. We therefore hypothesized that SWDs are not always associated with classically defined absence seizures or CPSs. To test this hypothesis, we used operant conditioning in male rats to determine whether outbred strains, Sprague Dawley and Long-Evans, and/or the inbred WAG/Rij strain (a rat model of heritable human absence epilepsy) could exercise voluntary control over these epileptiform events. We discovered that both inbred and outbred rats could shorten the duration of SWDs to obtain a reward. These results indicate that SWD and associated immobility in rats may not reflect the obvious cognitive/behavioral interruption classically associated with absence seizures or CPSs in humans. One interpretation of these results is that human absence seizures and perhaps CPSs could permit a far greater degree of cognitive capacity than often assumed and might be brought under voluntary control in some cases. However, these results also suggest that SWDs and associated immobility may be nonepileptic in healthy outbred rats and reflect instead voluntary rodent behavior unrelated to genetic manipulation or to brain trauma.SIGNIFICANCE STATEMENT Our evidence that inbred and outbred rats learn to control the duration of spike-wave discharges (SWDs) suggests a voluntary behavior with maintenance of consciousness. If SWDs model mild absence seizures and/or complex partial seizures in humans, then an opportunity may exist for operant control complementing or in some cases replacing medication. Their equal occurrence in outbred rats also implies a major potential confound for behavioral neuroscience experiments, at least in adult rats where SWDs are prevalent. Alternatively, the presence and voluntary control of SWDs in healthy outbred rats could indicate that these phenomena do not always model heritable absence epilepsy or post-traumatic epilepsy in humans, and may instead reflect typical rodent behavior.

Optimal frequency for powering millimeter-sized biomedical implants inside an inductively-powered homecage.

This paper presents the optimal design and operation frequency (f) of an inductively-powered homecage for powering biomedical devices with millimeter (mm) dimensions, implanted inside the body of freely-behaving small animal subjects, for longitudinal behavioral neuroscience and electrophysiology experiments. In order to improve the power transmission efficiency (PTE) for powering mm-sized implants, the geometry of the multi-coil inductive links in the form of 3- and 4-coil links as well as fp need to be co-optimized. A simplified equation for the PTE of 3-coil inductive links for powering mm-sized implants has been derived, based on which the optimal geometries and fp of a 3-coil link have been found using a commercial field solver (HFSS). In simulations, the optimized 3-coil inductive link achieved a significant PTE of 2.56% at the optimal fp of 40 MHz for powering a 1 mm3 implant coil at the nominal height of 7 cm, thanks to the link and fp optimization as well as an intermediate coil in the receiver side with 18 mm diameter.

A Smart Wirelessly Powered Homecage for Long-Term High-Throughput Behavioral Experiments.

A wirelessly powered homecage system, called the EnerCage-HC, that is equipped with multicoil wireless power transfer, closed-loop power control, optical behavioral tracking, and a graphic user interface is presented for longitudinal electrophysiology and behavioral neuroscience experiments. The EnerCage-HC system can wirelessly power a mobile unit attached to a small animal subject and also track its behavior in real-time as it is housed inside a standard homecage. The EnerCage-HC system is equipped with one central and four overlapping slanted wire-wound coils with optimal geometries to form three- and four-coil power transmission links while operating at 13.56 MHz. Utilizing multicoil links increases the power transfer efficiency (PTE) compared with conventional two-coil links and also reduces the number of power amplifiers to only one, which significantly reduces the system complexity, cost, and heat dissipation. A Microsoft Kinect installed 90 cm above the homecage localizes the animal position and orientation with 1.6-cm accuracy. Moreover, a power management ASIC, including a high efficiency active rectifier and automatic coil resonance tuning, was fabricated in a 0.35-μm 4M2P standard CMOS process for the mobile unit. The EnerCage-HC achieves a max/min PTE of 36.3%/16.1% at the nominal height of 7 cm. In vivo experiments were conducted on freely behaving rats by continuously delivering 24 mW to the mobile unit for >7 h inside a standard homecage.

Estimating latent attentional states based on simultaneous binary and continuous behavioral measures.

Cognition is a complex and dynamic process. It is an essential goal to estimate latent attentional states based on behavioral measures in many sequences of behavioral tasks. Here, we propose a probabilistic modeling and inference framework for estimating the attentional state using simultaneous binary and continuous behavioral measures. The proposed model extends the standard hidden Markov model (HMM) by explicitly modeling the state duration distribution, which yields a special example of the hidden semi-Markov model (HSMM). We validate our methods using computer simulations and experimental data. In computer simulations, we systematically investigate the impacts of model mismatch and the latency distribution. For the experimental data collected from a rodent visual detection task, we validate the results with predictive log-likelihood. Our work is useful for many behavioral neuroscience experiments, where the common goal is to infer the discrete (binary or multinomial) state sequences from multiple behavioral measures.

Adequacy of Control Comparisons in Olfactory Experiments

This paper describes the unique problems associated with selecting appropriate control conditions when designing olfactory experiments. Olfactory experiments are compared to behavioral neuroscience experiments in which a sham operation is used as a control condition. These comparisons point out the difficulty of using no-odor control conditions in olfactory experiments since they cannot provide adequate context for assessing nonspecific treatment effects. Demand characteristics in olfactory experiments are also discussed, and nomenclature is introduced to help guide the process of selecting good control conditions. In addition, a discussion of the selection of appropriate odors for control conditions is presented along with suggestions for strategies to create better olfactory experiments.

Different behavioral effects of neurotoxic dorsal hippocampal lesions placed under either isoflurane or propofol anesthesia

Anesthetic protocols for behavioral neuroscience experiments are evolving as new anesthetics are developed and surgical procedures are refined to improve animal welfare. We tested whether neurotoxic dorsal hippocampal lesions produced under two different anesthetic protocols would have different behavioral and/or histo-pathological effects. Rats were anesthetized with either propofol, an intravenous anesthetic, or isoflurane, a gaseous anesthetic, and multiple injections of an excitotoxin (N-methyl-d-aspartate) were stereotaxically placed in the dorsal hippocampus bilaterally. Intraoperative physiological parameters were similar in the two surgical groups, as were the volumes of the lesions, although the profile of postoperative impairment in a spatial learning task differed between the lesion groups depending on the anesthetic regimen used. These results show that the choice of anesthetic protocol is a critical variable in designing behavioral neuroscience experiments using neurosurgical procedures. This factor should be considered carefully in experimental design and in cross-study comparisons of lesion effects on behavior. © 2007 Wiley-Liss, Inc.