Publications by authors named "P J Magill"

Article Synopsis
  • Astrocytes play crucial and underestimated roles in modulating neuronal circuits, particularly in the striatum, where they regulate dopamine transmission and interact closely with cholinergic interneurons (ChIs).
  • The study reveals that striatal astrocytes rapidly excite ChIs and influence dopamine release through nicotinic acetylcholine receptors, operating on very fast timescales.
  • A unique anatomical configuration is observed, where ChI somata are closely located to astrocyte somata, allowing for a dynamic interaction that regulates ChI excitability and extracellular calcium, thus impacting overall striatal circuit activity and dopamine signaling.
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Article Synopsis
  • Identifying early events in neurodegenerative disorders, like Huntington's disease (HD), is essential for creating preventive treatments, particularly focusing on the role of dysfunctional indirect pathway spiny projection neurons (iSPNs) and increased dopamine levels.
  • The study reveals that genetic disruption of iSPN function in mice leads to heightened levels of striatal dopamine, potentially causing early symptoms like hyperkinesia, before observable dysfunction occurs.
  • By analyzing iSPNs, researchers found that reducing the protein GSTO2 could prevent dopaminergic issues and delay hyperkinetic symptoms, highlighting the significance of maintaining dopamine balance in HD progression.
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Defining spatial synchronisation of pathological beta oscillations is important, given that many theories linking them to parkinsonian symptoms propose a reduction in the dimensionality of the coding space within and/or across cortico-basal ganglia structures. Such spatial synchronisation could arise from a single process, with widespread entrainment of neurons to the same oscillation. Alternatively, the partially segregated structure of cortico-basal ganglia loops could provide a substrate for multiple ensembles that are independently synchronized at beta frequencies.

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Midbrain dopamine neurons are thought to play key roles in learning by conveying the difference between expected and actual outcomes. Recent evidence suggests diversity in dopamine signaling, yet it remains poorly understood how heterogeneous signals might be organized to facilitate the role of downstream circuits mediating distinct aspects of behavior. Here, we investigated the organizational logic of dopaminergic signaling by recording and labeling individual midbrain dopamine neurons during associative behavior.

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The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomic evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum.

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