Striatal dopamine signals reflect perceived cue-action-outcome associations in mice.

Striatal dopamine drives associative learning by acting as a teaching signal. Much work has focused on simple learning paradigms, including Pavlovian and instrumental learning. However, higher cognition requires that animals generate internal concepts of their environment, where sensory stimuli, actions and outcomes become flexibly associated.

The neuronal implementation of representational geometry in primate prefrontal cortex.

Modern neuroscience has seen the rise of a population-doctrine that represents cognitive variables using geometrical structures in activity space. Representational geometry does not, however, account for how individual neurons implement these representations. Leveraging the principle of sparse coding, we present a framework to dissect representational geometry into biologically interpretable components that retain links to single neurons.

Human acute microelectrode array recordings with broad cortical access, single-unit resolution, and parallel behavioral monitoring.

There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level.

Resolving the prefrontal mechanisms of adaptive cognitive behaviors: A cross-species perspective.

The prefrontal cortex (PFC) enables a staggering variety of complex behaviors, such as planning actions, solving problems, and adapting to new situations according to external information and internal states. These higher-order abilities, collectively defined as adaptive cognitive behavior, require cellular ensembles that coordinate the tradeoff between the stability and flexibility of neural representations. While the mechanisms underlying the function of cellular ensembles are still unclear, recent experimental and theoretical studies suggest that temporal coordination dynamically binds prefrontal neurons into functional ensembles.

Structuring of Abstract Working Memory Content by Fronto-parietal Synchrony in Primate Cortex.

How is neuronal activity across distant brain regions orchestrated to allow multiple stimuli to be stored together in working memory, yet maintained separate for individual readout and protection from distractors? Using paired recordings in the prefrontal and parietal cortex of monkeys discriminating numbers of items (numerosities), we found that working memory content is structured by frequency-specific oscillatory synchrony. Parieto-frontal signaling in the beta band carried information about the most recent numerical input. Fronto-parietal coupling in the theta band differentiated between multiple memorized numerosities.

Monoaminergic Neuromodulation of Sensory Processing.

All neuronal circuits are subject to neuromodulation. Modulatory effects on neuronal processing and resulting behavioral changes are most commonly reported for higher order cognitive brain functions. Comparatively little is known about how neuromodulators shape processing in sensory brain areas that provide the signals for downstream regions to operate on.

Doping the Mind: Dopaminergic Modulation of Prefrontal Cortical Cognition.

The prefrontal cortex is the center of cognitive control. Processing in prefrontal cortical circuits enables us to direct attention to behaviorally relevant events; to memorize, structure, and categorize information; and to learn new concepts. The prefrontal cortex receives strong projections from midbrain neurons that use dopamine as a transmitter.

Cell-type-specific modulation of targets and distractors by dopamine D1 receptors in primate prefrontal cortex.

The prefrontal cortex (PFC) is crucial for maintaining relevant information in working memory and resisting interference. PFC neurons are strongly regulated by dopamine, but it is unknown whether dopamine receptors are involved in protecting target memories from distracting stimuli. We investigated the prefrontal circuit dynamics and dopaminergic modulation of targets and distractors in monkeys trained to ignore interfering stimuli in a delayed-match-to-numerosity task.

Dopamine receptors differentially enhance rule coding in primate prefrontal cortex neurons.

Flexibly applying abstract rules is a hallmark feature of executive functioning represented by prefrontal cortex (PFC) neurons. Prefrontal networks are regulated by the neuromodulator dopamine, but how dopamine modulates high-level executive functions remains elusive. In monkeys performing a rule-based decision task, we report that both dopamine D1 and D2 receptors facilitated rule coding of PFC neurons, albeit by distinct physiological mechanisms.

Complementary roles for primate frontal and parietal cortex in guarding working memory from distractor stimuli.

Prefrontal cortex (PFC) and posterior parietal cortex are important for maintaining behaviorally relevant information in working memory. Here, we challenge the commonly held view that suppression of distractors by PFC neurons is the main mechanism underlying the filtering of task-irrelevant information. We recorded single-unit activity from PFC and the ventral intraparietal area (VIP) of monkeys trained to resist distracting stimuli in a delayed-match-to-numerosity task.

Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern.

Dopamine regulates two classes of primate prefrontal neurons that represent sensory signals.

The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing.

Relating magnitudes: the brain's code for proportions.

Whereas much is known about how we categorize and reason based on absolute quantity, data exploring ratios of quantities, as in proportions and fractions, are comparatively sparse. Until recently, it remained elusive whether these two representations of number are connected, how proportions are implemented by neurons and how language shapes this code. New data derived with complementary methods and from different model systems now shed light on the mechanisms of magnitude ratio representations.

Involuntary eyelid closure after STN-DBS: evidence for different pathophysiological entities.

Objective: Involuntary eyelid closure (IEC) may occur after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) and is often categorised as apraxia of lid opening (ALO), albeit the appropriateness of this term is under debate. To gain insight into the hitherto undefined pathophysiology of IEC after STN-DBS, we performed a comprehensive clinical and electrophysiological characterisation of lid function in a total of six PD patients.

Methods: The study was carried out in six PD patients who developed IEC after STN-DBS.

Tuning to non-symbolic proportions in the human frontoparietal cortex.

Humans share with many species a non-verbal system to estimate absolute quantity. This sense of number has been linked to the activity of quantity-selective neurons that respond maximally to preferred numerosities. With functional magnetic resonance imaging adaptation, we now show that populations of neurons in the human parietal and frontal cortex are also capable of encoding quantity ratios, or proportions, using the same non-verbal analog code as for absolute number.

Notation-independent representation of fractions in the human parietal cortex.

Although the concept of whole numbers is intuitive and well suited for counting and ordering, it is with the invention of fractions that the number system gained precision and flexibility. Absolute magnitude is encoded by single neurons that discharge maximally to specific numbers. However, it is unknown how the ratio of two numbers is represented, whether by processing numerator and denominator in separation, or by extending the analog magnitude code to relative quantity.

Extra-adrenal paravertebral myelolipoma mimicking a thoracic schwannoma.

Myelolipoma of the adrenal gland is composed of both adipose tissue and normal haematopoietic elements. Extra-adrenal myelolipomas are rare. We present the case of a 63-year-old female patient with adenoma of the adrenal gland and an additional paravertebral lesion in the thoracic spine.

The ABC of cardinal and ordinal number representations.

Numerical cognition encompasses the concepts of quantity ('how many?') and serial order ('which position?'). Yet, although numbers can convey different meanings, a recent imaging study by Fias and coworkers showed that ranking letters in the alphabet is subserved by a cortical network highly similar to that involved in judging magnitudes. In terms of neural processing, quantity and rank might just be two sides of the same coin.

Naive CD4+ T cells from lupus-prone Fas-intact MRL mice display TCR-mediated hyperproliferation due to intrinsic threshold defects in activation.

Autoreactive T cell activation is a consistent feature of murine lupus; however, the mechanism of such activation remains unclear. We hypothesized that naive CD4+ T cells in lupus have a lower threshold of activation through their TCR-CD3 complex that renders them more susceptible to stimulation with self-Ags. To test this hypothesis, we compared proliferation, IL-2 production, and single cell calcium signaling of naive CD4+ T cells isolated from Fas-intact MRL/+(Fas-lpr) mice with H-2k-matched B10.

Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons.

Ca2+ signals in neurons use specific temporal and spatial patterns to encode unambiguous information about crucial cellular functions. To understand the molecular basis for initiation and propagation of inositol 1,4,5-trisphosphate (InsP3)-mediated intracellular Ca2+ signals, we correlated the subcellular distribution of components of the InsP3 pathway with measurements of agonist-induced intracellular Ca2+ transients in cultured rat hippocampal neurons and pheochromocytoma cells. We found specialized domains with high levels of phosphatidylinositol-4-phosphate kinase (PIPKI) and chromogranin B (CGB), proteins acting synergistically to increase InsP3 receptor (InsP3R) activity and sensitivity.