Striatal indirect pathway mediates hesitation.

Determining the best possible action in an uncertain situation is often challenging, and organisms frequently need extra time to deliberate. This pause in behavior in response to uncertainty - also known as hesitation - commonly occurs in many aspects of daily life, yet its neural circuits are poorly understood. Here we present the first experimental paradigm that reliably evokes hesitation in mice.

Motor cortex is responsible for motoric dynamics in striatum and the execution of both skilled and unskilled actions.

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions.

An Investigation of Parameter-Dependent Cell-Type Specific Effects of Transcranial Focused Ultrasound Stimulation Using an Awake Head-Fixed Rodent Model.

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique able to target shallow and deep brain structures with high precision. Previous studies have demonstrated that tFUS stimulation responses are both cell-type specific and controllable through altering stimulation parameters. Specifically, tFUS can elicit time-locked neural activity in regular spiking units (RSUs) that is sensitive to increases in pulse repetition frequency (PRF), while time-locked responses are not seen in fast spiking units (FSUs).

Deep behavioural phenotyping of the Q175 Huntington disease mouse model: effects of age, sex, and weight.

Background: Huntington disease (HD) is a neurodegenerative disorder with complex motor and behavioural manifestations. The Q175 knock-in mouse model of HD has gained recent popularity as a genetically accurate model of the human disease. However, behavioural phenotypes are often subtle and progress slowly in this model.

Mimicking opioid analgesia in cortical pain circuits.

The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive.

Forebrain EAAT3 Overexpression Increases Susceptibility to Amphetamine-Induced Repetitive Behaviors.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown the association of polymorphisms in the gene with OCD. The most common of these OCD-associated polymorphisms increases the expression of the encoded protein, excitatory amino acid transporter 3 (EAAT3), a neuronal glutamate transporter.

A-SOiD, an active-learning platform for expert-guided, data-efficient discovery of behavior.

To identify and extract naturalistic behavior, two methods have become popular: supervised and unsupervised. Each approach carries its own strengths and weaknesses (for example, user bias, training cost, complexity and action discovery), which the user must consider in their decision. Here, an active-learning platform, A-SOiD, blends these strengths, and in doing so, overcomes several of their inherent drawbacks.

Mapping the neuroethological signatures of pain, analgesia, and recovery in mice.

Ongoing pain is driven by the activation and modulation of pain-sensing neurons, affecting physiology, motor function, and motivation to engage in certain behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in non-verbal animals. Here, in mice, we used site-specific electrophysiology to define key time points corresponding to peripheral sensitivity in acute paw inflammation and chronic knee pain models.

Open-source tools for behavioral video analysis: Setup, methods, and best practices.

Recently developed methods for video analysis, especially models for pose estimation and behavior classification, are transforming behavioral quantification to be more precise, scalable, and reproducible in fields such as neuroscience and ethology. These tools overcome long-standing limitations of manual scoring of video frames and traditional 'center of mass' tracking algorithms to enable video analysis at scale. The expansion of open-source tools for video acquisition and analysis has led to new experimental approaches to understand behavior.

Recent Advances in 3D Printing of Biomedical Sensing Devices.

Additive manufacturing, also called 3D printing, is a rapidly evolving technique that allows for the fabrication of functional materials with complex architectures, controlled microstructures, and material combinations. This capability has influenced the field of biomedical sensing devices by enabling the trends of device miniaturization, customization, and elasticity (i.e.

CMU Array: A 3D nanoprinted, fully customizable high-density microelectrode array platform.

Microelectrode arrays provide the means to record electrophysiological activity critical to brain research. Despite its fundamental role, there are no means to customize electrode layouts to address specific experimental or clinical needs. Moreover, current electrodes demonstrate substantial limitations in coverage, fragility, and expense.

Contralateral Limb Specificity for Movement Preparation in the Parietal Reach Region.

The canonical view of motor control is that distal musculature is controlled primarily by the contralateral cerebral hemisphere; unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. To distinguish between these possibilities, we serially inactivated the parietal reach region, comprising the posterior portion of medial intraparietal area, the anterior portion of V6a, and portions of the lateral occipital parietal area, in each hemisphere of 2 monkeys (23 experimental sessions, 46 injections total) to evaluate parietal reach region's contribution to the contralateral reaching deficits observed following lateralized brain lesions.

B-SOiD, an open-source unsupervised algorithm for identification and fast prediction of behaviors.

Studying naturalistic animal behavior remains a difficult objective. Recent machine learning advances have enabled limb localization; however, extracting behaviors requires ascertaining the spatiotemporal patterns of these positions. To provide a link from poses to actions and their kinematics, we developed B-SOiD - an open-source, unsupervised algorithm that identifies behavior without user bias.

The two-step task, avoidance, and OCD.

In this invited review, we argue for the need to determine whether appetitive and aversive behaviors, be they goal-directed or habitual, share overlapping neural circuitry. To motivate our argument, we first summarize what is currently known about the neural circuits governing aversive and appetitive behaviors by focusing first on the three hypothesized phases of avoidance learning, and then on goal-directed and habitual reward seeking. We then provide several reasons to believe that the neural circuits of appetitive and aversive instrumental behaviors are not completely overlapping.

Open-Source Joystick Manipulandum for Decision-Making, Reaching, and Motor Control Studies in Mice.

To make full use of optogenetic and molecular techniques in the study of motor control, rich behavioral paradigms for rodents must rise to the same level of sophistication and applicability. We describe the layout, construction, use and analysis of data from joystick-based reaching in a head-fixed mouse. The step-by-step guide is designed for both experienced rodent motor labs and new groups looking to enter into this research space.

Translating Insights From Optogenetics To Therapies For Parkinson's Disease.

Movement disorders including Parkinson’s disease and dystonia are caused by neurological dysfunction, typically resulting from the loss of a neuronal input within a circuit. Neuromodulation, specifically deep brain stimulation (DBS), has proven to be a critical development in the treatment of movement disorders. Continuing efforts aim to improve DBS techniques, both in how they exert their effects and in the efficacy of the mechanism involved in eliciting those effects.

A Proposed Circuit Computation in Basal Ganglia: History-Dependent Gain.

In this Scientific Perspectives we first review the recent advances in our understanding of the functional architecture of basal ganglia circuits. Then we argue that these data can best be explained by a model in which basal ganglia act to control the gain of movement kinematics to shape performance based on prior experience, which we refer to as a history-dependent gain computation. Finally, we discuss how insights from the history-dependent gain model might translate from the bench to the bedside, primarily the implications for the design of adaptive deep brain stimulation.

Opponent and bidirectional control of movement velocity in the basal ganglia.

For goal-directed behaviour it is critical that we can both select the appropriate action and learn to modify the underlying movements (for example, the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behaviour, such as the neocortex and thalamus, are integrated with reward signalling to reinforce successful, purposive actions. The dorsal striatum, a major input structure of basal ganglia, is composed of two opponent pathways, direct and indirect, thought to select actions that elicit positive outcomes and suppress actions that do not, respectively.

The parietal reach region is limb specific and not involved in eye-hand coordination.

Primates frequently reach toward visual targets. Neurons in early visual areas respond to stimuli in the contralateral visual hemifield and without regard to which limb will be used to reach toward that target. In contrast, neurons in motor areas typically respond when reaches are performed using the contralateral limb and with minimal regard to the visuospatial location of the target.

Lesions of cortical area LIP affect reach onset only when the reach is accompanied by a saccade, revealing an active eye-hand coordination circuit.

The circuits that drive visually guided eye and arm movements transform generic visual inputs into effector-specific motor commands. As part of the effort to elucidate these circuits, the primate lateral intraparietal area (LIP) has been interpreted as a priority map for saccades (oculomotor-specific) or a salience map of space (not effector-specific). It has also been proposed as a locus for eye-hand coordination.

Intention and attention: different functional roles for LIPd and LIPv.

Establishing the circuitry underlying attentional and oculomotor control is a long-standing goal of systems neuroscience. The macaque lateral intraparietal area (LIP) has been implicated in both processes, but numerous studies have produced contradictory findings. Anatomically, LIP consists of a dorsal and ventral subdivision, but the functional importance of this division remains unclear.

Intermittent ethanol exposure in adolescent rats: dose-dependent impairments in trace conditioning.

Background: Recent studies have revealed that the adolescent brain may be especially vulnerable to ethanol-induced toxicity. Corticolimbic regions are more severely damaged following ethanol exposure during adolescence than during adulthood. The consequences of adolescent ethanol exposure on cognition however, have only recently begun to be explored.