Oligodendrocytes and myelin limit neuronal plasticity in visual cortex.

Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity.

Adolescent oligodendrogenesis and myelination restrict experience-dependent neuronal plasticity in adult visual cortex.

Background: Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this hypothesis in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity.

Motor learning revamps the myelin landscape.

Learning requires new oligodendrogenesis, but how myelin patterns change during learning is unclear. Bacmeister et al. show that motor learning induces phase-specific changes in myelination on behaviorally activated axons that correlate with motor performance, suggesting myelin remodeling is involved in learning.

Validating visual evoked potentials as a preclinical, quantitative biomarker for remyelination efficacy.

Many biomarkers in clinical neuroscience lack pathological certification. This issue is potentially a significant contributor to the limited success of neuroprotective and neurorestorative therapies for human neurological disease-and is evident even in areas with therapeutic promise such as myelin repair. Despite the identification of promising remyelinating candidates, biologically validated methods to demonstrate therapeutic efficacy or provide robust preclinical evidence of remyelination in the CNS are lacking.

Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice.

In humans, loss-of-function mutations in the UBE3A gene lead to the neurodevelopmental disorder Angelman syndrome (AS). AS patients have severe impairments in speech, learning and memory, and motor coordination, for which there is currently no treatment. In addition, UBE3A is duplicated in > 1-2% of patients with autism spectrum disorders-a further indication of the significant role it plays in brain development.

Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease.

Severe cognitive decline is a hallmark of Alzheimer's disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the dynamics of myelin generation and loss in the APP/PS1 mouse model of AD.

TDP-43 maximizes nerve conduction velocity by repressing a cryptic exon for paranodal junction assembly in Schwann cells.

TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic delay in peripheral nerve conduction causing significant motor deficits in mice, which is directly attributed to the absence of paranodal axoglial junctions.

Myelin plasticity: sculpting circuits in learning and memory.

Throughout our lifespan, new sensory experiences and learning continually shape our neuronal circuits to form new memories. Plasticity at the level of synapses has been recognized and studied for decades, but recent work has revealed an additional form of plasticity - affecting oligodendrocytes and the myelin sheaths they produce - that plays a crucial role in learning and memory. In this Review, we summarize recent work characterizing plasticity in the oligodendrocyte lineage following sensory experience and learning, the physiological and behavioural consequences of manipulating that plasticity, and the evidence for oligodendrocyte and myelin dysfunction in neurodevelopmental disorders with cognitive symptoms.

Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons.

Electrical or optogenetic stimulation of lateral hypothalamic (LH) GABA neurons induces rapid vigorous eating in sated animals. The dopamine system has been implicated in the regulation of feeding. Previous work has suggested that a subset of LH GABA neurons projects to the ventral tegmental area (VTA) and targets GABA neurons, inhibiting them and thereby disinhibiting dopaminergic activity and release.

That Wasn't a Complement-Too Much C3 in Demyelinating Disease.

Multiple sclerosis is a chronic inflammatory disease characterized by demyelination in the central nervous system. In this issue of Immunity, Werneberg et al. report a striking loss of synapses driven by excessive microglial pruning early in demyelinating disease, which can be rescued by inhibiting the complement component C3.

Oligodendrocytes Support Neuronal Glutamatergic Transmission via Expression of Glutamine Synthetase.

Glutamate has been implicated in a wide range of brain pathologies and is thought to be metabolized via the astrocyte-specific enzyme glutamine synthetase (GS). We show here that oligodendrocytes, the myelinating glia of the central nervous system, also express high levels of GS in caudal regions like the midbrain and the spinal cord. Selective removal of oligodendrocyte GS in mice led to reduced brain glutamate and glutamine levels and impaired glutamatergic synaptic transmission without disrupting myelination.

Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling.

Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of CNS vasculature. Yet, despite the essential functional roles they fill, very little is known about the physiology of astrocytes in the ventral midbrain, a region that houses dopamine-releasing neurons and is critical for reward learning and motivated behaviors. Here, using a combination of whole-transcriptome sequencing, histology, slice electrophysiology, and calcium imaging, we performed the first functional and molecular profiling of ventral midbrain astrocytes and observed numerous differences between these cells and their telencephalic counterparts, both in their gene expression profile and in their physiological properties.

Functional Astrocyte Heterogeneity and Implications for Their Role in Shaping Neurotransmission.

In recent years, the role of astrocytes in shaping neuronal signaling has come to the forefront of neuroscience research. The development of genetic tools that enable targeted manipulation of astrocytes has revealed a wealth of mechanisms by which they can alter the synaptic strength and intrinsic excitability of neurons in behaviorally relevant ways. In parallel, several studies have demonstrated significant variability in the gene expression and physiology of astrocytes within and between brain regions.

VTA dopamine neuron plasticity - the unusual suspects.

Dopamine neurons in the ventral tegmental area (VTA) are involved in a variety of physiological and pathological conditions, ranging from motivated behaviours to substance use disorders. While many studies have shown that these neurons can express plasticity at excitatory and inhibitory synapses, little is known about how inhibitory inputs and glial activity shape the output of DA neurons and therefore, merit greater discussion. In this review, we will attempt to fill in a bit more of the puzzle, with a focus on inhibitory transmission and astrocyte function.