Cellular/Molecular
Nfasc Coordinates Pinceau Synapse Formation from Both Ends
Elizabeth D. Buttermore, Claire Piochon, Michael L. Wallace, Benjamin D. Philpot, Christian Hansel et al.
(see pages 4724–4742)
Although cell adhesion molecules may not seem all that glamorous, Buttermore et al. have found pivotal roles for Neurofascin (Nfasc) on both sides of a critical cerebellar synapse. Basket interneuron axon collaterals form an inhibitory synapse, called the pinceau, on the axon initial segment (AIS) of Purkinje cells, the cerebellum's only output neurons. Nfasc has been previously implicated in organization and maintenance of the pinceau. The authors made transgenic mice with Nfasc conditionally knocked out during development. They found that when Purkinje cells lost Nfasc, AIS maturation and pinceau formation went awry, spontaneous Purkinje activity was lost, and inhibitory inputs were diminished. The additional loss of Nfasc from basket interneurons caused improper axon branching and poor targeting to Purkinje neurons. Without the pinceau's inhibitory regulation, Purkinje cells degenerated and animals became severely ataxic. The work supports important—even glamorous—roles for the molecule in coordinating pinceau formation.
Development/Plasticity/Repair
Radial Glia Identified as Source of Neocortical Astrocytes
Sanjay Magavi, Drew Friedmann, Garrett Banks, Alberto Stolfi, and Carlos Lois
(see pages 4762–4772)
Astrocytes, once vaguely described as “neuronal support cells,” are fast gaining appreciation as critical—and diverse—cells during neurodevelopment and throughout the life of the brain. As details about astrocytes' many roles are elucidated, so are their origins. Fate-mapping experiments have been instrumental in determining how cells arise, differentiate, and migrate to their destinations. To establish the source of cortical astrocytes, Magavi et al. sparsely expressed Cre in the brains of transgenic mice to label a small, apparently random population of brain precursor cells and their progeny. They identified radial glial cells—which give rise to cortical pyramidal neurons—as the precursors of protoplasmic astrocytes within the neocortex. Their findings reflect a growing realization that astrocytes probably do not arise from a homogeneous population at the subventricular zone and then fan out across the brain. Instead, the term “astrocytes” seems to describe many highly specialized, regionally distinct cell types that are locally grown, so to speak.
Behavioral/Systems/Cognitive
Functionally Distinct Subregions in Human Entorhinal Cortex
Heidrun Schultz, Tobias Sommer, and Jan Peters
(see pages 4716–4723)
The medial temporal lobe (MTL) processes episodic memory in multiple parallel streams. In animals, anatomically distinct MTL pathways between the visual cortex and hippocampus have been mapped. Could these pathways be distinguished by content in humans? Schultz et al. used high-resolution functional magnetic resonance imaging (fMRI) to investigate. In people engaged in a working memory task, interruption of active rehearsal followed by recall is marked by a flurry of MTL activity visible with fMRI. The authors used this clue to zoom in on the region. Subjects were presented with a working memory task using spatial or non-spatial images of outdoor scenes or faces. Trials were interrupted by a distraction task that took attention away from the job at hand. The authors identified discrete content-related pathways: a parahippocampal-medial entorhinal cortex pathway was associated with spatial content while a perirhinal-lateral entorhinal cortex stream responded to non-spatial information. The work provides evidence for functionally specialized regions within human entorhinal cortex.
Neurobiology of Disease
Network Bursts Driven by Stochastic, Deterministic Processes
Hajime Takano, Melissa McCartney, Pavel I. Ortinski, Cuiyong Yue, Mary E. Putt, et al.
(see pages 4743–4754)
Spontaneous bursting of neural networks appears in brain development and in pathologies such as epilepsy. Neither their purpose nor their source is completely understood; the nature of whole-network activity makes it difficult to determine whether stochastic, deterministic, or mixed processes drive the activity. Takano et al. combined multicellular calcium imaging with fast confocal microscopy to tease out the origins of spontaneous network bursts in developing mouse and rat hippocampus. They examined two burst types: giant depolarizing potentials (GDPs) and spontaneous interictal bursts. Their methods allowed them to see whether specific neurons might be inciting the group to action or whether all the neurons act truly simultaneously. GDPs appeared to be driven by a specialized subset of about 5% of neurons in a deterministic process. Interictal bursts in contrast arose from stochastic events by a homogeneous population of neurons with interchangeable roles.