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1.
Front Hum Neurosci ; 17: 1146242, 2023.
Article in English | MEDLINE | ID: mdl-37228852
2.
BMJ Case Rep ; 16(3)2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36948522

ABSTRACT

Panic attacks have been associated with hypophosphatemia, which can lead to numerous complications if unrecognised. Here, we present the case of an otherwise-healthy man in his 20s who experienced a panic attack accompanied by hypophosphatemia and hypokalaemia and subsequently developed rhabdomyolysis. This trajectory highlights the clinical significance of panic attack-associated metabolic derangements and their potential for medical complications such as rhabdomyolysis.


Subject(s)
Hypokalemia , Hypophosphatemia , Panic Disorder , Male , Humans , Panic Disorder/complications , Hypokalemia/complications , Hypophosphatemia/complications , Panic
4.
Nat Commun ; 10(1): 3128, 2019 07 16.
Article in English | MEDLINE | ID: mdl-31311934

ABSTRACT

To select actions based on sensory evidence, animals must create and manipulate representations of stimulus information in memory. Here we report that during accumulation of somatosensory evidence, optogenetic manipulation of cerebellar Purkinje cells reduces the accuracy of subsequent memory-guided decisions and causes mice to downweight prior information. Behavioral deficits are consistent with the addition of noise and leak to the evidence accumulation process. We conclude that the cerebellum can influence the accurate maintenance of working memory.


Subject(s)
Cerebellum/physiology , Decision Making/physiology , Memory, Short-Term/physiology , Animals , Behavior, Animal/physiology , Cerebellum/cytology , Cerebellum/injuries , Craniotomy , Female , Male , Mice , Models, Animal , Optogenetics , Photic Stimulation , Purkinje Cells/physiology
5.
Elife ; 72018 09 20.
Article in English | MEDLINE | ID: mdl-30226467

ABSTRACT

Cognitive and social capacities require postnatal experience, yet the pathways by which experience guides development are unknown. Here we show that the normal development of motor and nonmotor capacities requires cerebellar activity. Using chemogenetic perturbation of molecular layer interneurons to attenuate cerebellar output in mice, we found that activity of posterior regions in juvenile life modulates adult expression of eyeblink conditioning (paravermal lobule VI, crus I), reversal learning (lobule VI), persistive behavior and novelty-seeking (lobule VII), and social preference (crus I/II). Perturbation in adult life altered only a subset of phenotypes. Both adult and juvenile disruption left gait metrics largely unaffected. Contributions to phenotypes increased with the amount of lobule inactivated. Using an anterograde transsynaptic tracer, we found that posterior cerebellum made strong connections with prelimbic, orbitofrontal, and anterior cingulate cortex. These findings provide anatomical substrates for the clinical observation that cerebellar injury increases the risk of autism.


Subject(s)
Autistic Disorder/physiopathology , Behavior, Animal/physiology , Cerebellum/physiology , Cognition/physiology , Animals , Brain Mapping , Cerebellum/diagnostic imaging , Disease Models, Animal , Humans , Image Processing, Computer-Assisted , Interneurons/physiology , Learning/physiology , Magnetic Resonance Imaging , Mice , Neural Pathways/physiology , Social Change
6.
Elife ; 72018 08 13.
Article in English | MEDLINE | ID: mdl-30102151

ABSTRACT

To make successful evidence-based decisions, the brain must rapidly and accurately transform sensory inputs into specific goal-directed behaviors. Most experimental work on this subject has focused on forebrain mechanisms. Using a novel evidence-accumulation task for mice, we performed recording and perturbation studies of crus I of the lateral posterior cerebellum, which communicates bidirectionally with numerous forebrain regions. Cerebellar inactivation led to a reduction in the fraction of correct trials. Using two-photon fluorescence imaging of calcium, we found that Purkinje cell somatic activity contained choice/evidence-related information. Decision errors were represented by dendritic calcium spikes, which in other contexts are known to drive cerebellar plasticity. We propose that cerebellar circuitry may contribute to computations that support accurate performance in this perceptual decision-making task.


Subject(s)
Cerebellum/physiology , Decision Making , Perception , Action Potentials , Animals , Behavior, Animal , Calcium Signaling , Female , Male , Mice , Neurons/physiology
7.
Cognition ; 179: 266-297, 2018 10.
Article in English | MEDLINE | ID: mdl-30064655

ABSTRACT

Previous work suggests that humans find it difficult to learn the structure of causal systems given observational data alone. We identify two conditions that enable successful structure learning from observational data: people succeed if the underlying causal system is deterministic, and if each pattern of observations has a single root cause. In four experiments, we show that either condition alone is sufficient to enable high levels of performance, but that performance is poor if neither condition applies. A fifth experiment suggests that neither determinism nor root sparsity takes priority over the other. Our data are broadly consistent with a Bayesian model that embodies a preference for structures that make the observed data not only possible but probable.


Subject(s)
Learning , Models, Psychological , Problem Solving , Bayes Theorem , Humans , Probability Learning
8.
Front Behav Neurosci ; 12: 36, 2018.
Article in English | MEDLINE | ID: mdl-29559900

ABSTRACT

The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.

9.
Nat Neurosci ; 20(5): 727-734, 2017 May.
Article in English | MEDLINE | ID: mdl-28319608

ABSTRACT

Cerebellar granule cells, which constitute half the brain's neurons, supply Purkinje cells with contextual information necessary for motor learning, but how they encode this information is unknown. Here we show, using two-photon microscopy to track neural activity over multiple days of cerebellum-dependent eyeblink conditioning in mice, that granule cell populations acquire a dense representation of the anticipatory eyelid movement. Initially, granule cells responded to neutral visual and somatosensory stimuli as well as periorbital airpuffs used for training. As learning progressed, two-thirds of monitored granule cells acquired a conditional response whose timing matched or preceded the learned eyelid movements. Granule cell activity covaried trial by trial to form a redundant code. Many granule cells were also active during movements of nearby body structures. Thus, a predictive signal about the upcoming movement is widely available at the input stage of the cerebellar cortex, as required by forward models of cerebellar control.


Subject(s)
Cerebellum/physiology , Feedback , Learning/physiology , Neurons/physiology , Animals , Anticipation, Psychological/physiology , Conditioning, Classical/physiology , Male , Mice , Mice, Transgenic
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