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Nature Mar 2024Astrocytes are heterogeneous glial cells of the central nervous system. However, the physiological relevance of astrocyte diversity for neural circuits and behaviour...
Astrocytes are heterogeneous glial cells of the central nervous system. However, the physiological relevance of astrocyte diversity for neural circuits and behaviour remains unclear. Here we show that a specific population of astrocytes in the central striatum expresses μ-crystallin (encoded by Crym in mice and CRYM in humans) that is associated with several human diseases, including neuropsychiatric disorders. In adult mice, reducing the levels of μ-crystallin in striatal astrocytes through CRISPR-Cas9-mediated knockout of Crym resulted in perseverative behaviours, increased fast synaptic excitation in medium spiny neurons and dysfunctional excitatory-inhibitory synaptic balance. Increased perseveration stemmed from the loss of astrocyte-gated control of neurotransmitter release from presynaptic terminals of orbitofrontal cortex-striatum projections. We found that perseveration could be remedied using presynaptic inhibitory chemogenetics, and that this treatment also corrected the synaptic deficits. Together, our findings reveal converging molecular, synaptic, circuit and behavioural mechanisms by which a molecularly defined and allocated population of striatal astrocytes gates perseveration phenotypes that accompany neuropsychiatric disorders. Our data show that Crym-positive striatal astrocytes have key biological functions within the central nervous system, and uncover astrocyte-neuron interaction mechanisms that could be targeted in treatments for perseveration.
Topics: Animals; Humans; Mice; Astrocytes; Corpus Striatum; Gene Editing; Gene Knockout Techniques; mu-Crystallins; Rumination, Cognitive; Synaptic Transmission; CRISPR-Cas Systems; Medium Spiny Neurons; Synapses; Prefrontal Cortex; Presynaptic Terminals; Neural Inhibition
PubMed: 38418885
DOI: 10.1038/s41586-024-07138-0 -
HCA Healthcare Journal of Medicine 2023Description As healthcare workers, invested in the wellbeing of our patients while also hoping to grow as individuals, we sometimes tend to view our jobs as a rigid...
Description As healthcare workers, invested in the wellbeing of our patients while also hoping to grow as individuals, we sometimes tend to view our jobs as a rigid duality-we are either "in love" with our practice and persevere flawlessly through all hardship, or we are "burnt out," coldhearted, and defeated by the heavy workload and expectations of medicine. In reality, we all sit somewhere in the middle of a blurry spectrum, balancing out physical, mental, and emotional pain with the immense honor of saving and cherishing human life, while simultaneously struggling to reconcile our altruistic goals with realistic but necessary human incentives. I want this open-ended work to acknowledge these challenging but critical "and yet" moments, and I hope anyone who is reading it can connect to the words personally and find new insight, regardless of where they are in life.
PubMed: 37753413
DOI: 10.36518/2689-0216.1507 -
Psychological Reports Feb 2018Procrastination has been described as the quintessence of self-regulatory failure. This study examines the relationships between this self-regulatory failure and other...
Procrastination has been described as the quintessence of self-regulatory failure. This study examines the relationships between this self-regulatory failure and other manifestations of self-regulation problems, namely impulsivity and intrusive thoughts. One hundred and forty-one participants completed questionnaires assessing procrastination, impulsivity (in particular, the urgency and lack of perseverance dimensions), and intrusive thoughts (i.e., rumination and daydreaming). Main results show that urgency mediated the association between rumination and procrastination, whereas rumination did not mediate the relation between urgency and procrastination. Lack of perseverance mediated the association between daydreaming and procrastination, and daydreaming mediated the relation between lack of perseverance and procrastination. This study highlights the role of impulsivity and intrusive thoughts in procrastination, specifies the links between these self-regulation problems, and provides insights into their (potential) underlying mechanisms. It also opens interesting prospects for management strategies for implementing targeted psychological interventions to reduce impulsive manifestations and/or thought control difficulties accompanying procrastination.
Topics: Adolescent; Adult; Female; Humans; Impulsive Behavior; Male; Procrastination; Rumination, Cognitive; Self-Control; Thinking; Young Adult
PubMed: 28776482
DOI: 10.1177/0033294117720695 -
Perfusion Oct 2022
PubMed: 35972907
DOI: 10.1177/02676591221120634 -
Handbook of Clinical Neurology 2015Palinacousis is derived from the Greek words palin, which means again or anew, and acousis, meaning hearing. It was first described by Jacobs et al. (1971), who defined... (Review)
Review
Palinacousis is derived from the Greek words palin, which means again or anew, and acousis, meaning hearing. It was first described by Jacobs et al. (1971), who defined the phenomenon as "an auditory illusion of perseveration or persistence of sound impressions for seconds, minutes, or hours after the cessation of auditory stimulation." The auditory perseveration does not occur spontaneously but is triggered by something in the environment. A limited number of cases have been described in the literature. This chapter describes the anatomic abnormalities that may cause this phenomenon, the clinical characteristics that define palinacousis, differential diagnosis and potential etiologies.
Topics: Acoustic Stimulation; Auditory Pathways; Auditory Perceptual Disorders; History, 18th Century; Humans; Illusions
PubMed: 25726284
DOI: 10.1016/B978-0-444-62630-1.00025-1 -
Handbook of Clinical Neurology 2023The motor phenomena accompanying frontal lobe disease are diverse, reflecting the various roles the frontal lobes play in the organization of motor control. The... (Review)
Review
The motor phenomena accompanying frontal lobe disease are diverse, reflecting the various roles the frontal lobes play in the organization of motor control. The principal frontal motor areas, the primary motor cortex, the premotor cortex, and the supplementary motor area, have different but interrelated functions in motor control. The principal efferent pathway of the primary motor cortex is the corticospinal tract which conducts fine motor control. Damage to the primary motor cortex and the corticospinal tract results in paralysis and loss of skilled, particularly distal, motor function. Lesions of the premotor cortex interfere with the preparation for the execution of movements and coordinating sequences of limb movement. Mediated through cortico-reticulospinal pathways, the premotor cortex adjusts axial and limb muscle activities. The fine motor skills of the corticospinal tract are superimposed upon these stabilizing movements. Supplementary motor area lesions interrupt self-initiated movements, release alien limb behaviors, and result in grasping. Paralysis, primitive reflexes, and frontal gait disorders are readily observed on examination, but difficulties initiating and sequencing movements are more subtle signs of perturbed higher motor control and require special examination procedures. Prefrontal motor syndromes include motor behaviors that only become apparent when the subject performs spontaneous or self-directed activities, unconstrained by instructions from the examiner. Clinical observation also reveals a slowness to respond to instruction with long delays before initiating action (inertia), but once underway they may be unable to stop (perseveration). Patients sit motionless without spontaneous movement or interest in their surrounds (apathy), yet exhibit distractibility, diverting attention to an incidental peripheral stimulus or an object with which they may then fiddle (environmental dependency and utilization behavior). Little spontaneous speech is initiated (abulia) but echolalia may be stimulated by the examiner's conversation. Restlessness, distractibility, perseveration, and environmentally dependent utilization behaviors coexist with apathy, inertia, and abulia. Mutism and akinesia may alternate with stereotypies and agitation in catatonia. These paradoxical combinations are of considerable diagnostic significance in recognizing frontal lobe motor syndromes.
Topics: Humans; Syndrome; Frontotemporal Dementia; Apathy; Motor Cortex; Paralysis
PubMed: 37620084
DOI: 10.1016/B978-0-323-98817-9.00008-9 -
The Journal of Pediatric Pharmacology... 2020Everyone who is successful in their career and in life has a story. While the storylines may differ from individual to individual, there is almost always something more...
Everyone who is successful in their career and in life has a story. While the storylines may differ from individual to individual, there is almost always something more to the plot than innate talents and skills. Obstacles, failures, and setbacks are common to everyone, but the successful somehow find a way to rebound, recover, and persevere. This editorial describes one such story of passion and grit of an award-winning pediatric pharmacist.
PubMed: 33214776
DOI: 10.5863/1551-6776-25.8.661 -
ELife Oct 2019After acknowledging that power differentials exist, can scientists find inspiration to persevere anyway?
After acknowledging that power differentials exist, can scientists find inspiration to persevere anyway?
Topics: Power, Psychological; Research Personnel; Sex Factors
PubMed: 31573511
DOI: 10.7554/eLife.52232 -
Fertility and Sterility Aug 2021
PubMed: 34246468
DOI: 10.1016/j.fertnstert.2021.06.003 -
Handbook of Clinical Neurology 2019The frontal lobes contain a complex set of diverse anatomic regions that form multiple distinct, complex networks with cortical and subcortical regions. Damage to these... (Review)
Review
The frontal lobes contain a complex set of diverse anatomic regions that form multiple distinct, complex networks with cortical and subcortical regions. Damage to these cortical-subcortical networks can have dramatic behavioral consequences, ranging from apathy to impairments in executive functioning. This chapter provides a brief overview of the common syndromes caused by damage to the mediodorsal and dorsolateral prefrontal circuits, followed by a more detailed review of the syndrome-sometimes referred to as pseudopsychopathy or acquired sociopathy-associated with damage to the ventromedial prefrontal circuit.
Topics: Agnosia; Apathy; Emotions; Executive Function; Frontal Lobe; Frontotemporal Dementia; Humans; Motivation; Nerve Net; Neuropsychological Tests
PubMed: 31590727
DOI: 10.1016/B978-0-12-804281-6.00008-2